Most recent papers:

• Incidence of mental health hospitalizations, treated self‐harm, and emergency room visits following new anxiety disorder diagnoses in privately insured U.S. children.
  Greta A. Bushnell, Bradley N. Gaynes, Scott N. Compton, Stacie B. Dusetzina, M. Alan Brookhart, Til Stürmer.
  Depression and Anxiety. October 24, 2018
  --- - |2+ Background Anxiety disorders are one of the most common mental illnesses in children and associated with high healthcare utilization. We aimed to estimate 2‐year cumulative incidence of mental health–related hospitalizations, treated self‐harm, and emergency room (ER) visits in children newly diagnosed with anxiety disorders and, for context, in children without anxiety disorders. Methods We identified commercially insured treatment naïve children (3–17 years) with a new office‐based anxiety disorder diagnosis (ICD‐9‐CM) from 2005–2014 in the MarketScan claims database. We followed children for up to 2 years after diagnosis for the first of each event: mental health–related hospitalization, inpatient, treated self‐harm, and ER visits (any, anxiety‐related, injury‐related). Children without anxiety diagnoses were included as comparators, matched on age, sex, date, and region. We estimated cumulative incidence of each event using Kaplan–Meier analysis. Results From 2005–2014, we identified 198,450 children with a new anxiety diagnosis. One‐year after anxiety diagnosis, 2.0% of children had a mental health–related hospitalization, 0.08% inpatient, treated self‐harm, 1.4% anxiety‐related ER visit, and 20% any ER visit; incidence was highest in older children with baseline comorbid depression. One‐year cumulative incidence of each event was lower in the comparison cohort without anxiety (e.g., mental health–related hospitalizations = 0.5%, treated self‐harm = 0.01%, and ER visits = 13%). Conclusions Given the prevalence of anxiety disorders, 2‐year incidence estimates translate to a significant number of children experiencing each event. Our findings offer caregivers, providers, and patients information to better understand the burden of anxiety disorders and can help anticipate healthcare utilization and inform efforts to prevent these serious events. - Depression and Anxiety, EarlyView.
  

  October 24, 2018   doi: 10.1002/da.22849   open full text
• Trajectories of grief, depression, and posttraumatic stress in disaster‐bereaved people.
  Lonneke I. M. Lenferink, Angela Nickerson, Jos Keijser, Geert E. Smid, Paul A. Boelen.
  Depression and Anxiety. October 19, 2018
  --- - |2+ Background Previous latent trajectory studies in adult bereaved people have identified individual differences in reactions postloss. However, prior findings may not reflect the complete picture of distress postloss, because they were focused on depression symptoms following nonviolent death. We examined trajectories of symptom‐levels of persistent complex bereavement disorder (PCBD), depression, and posttraumatic stress disorder (PTSD) in a disaster‐bereaved sample. We also investigated associations among these trajectories and background and loss‐related factors, psychological support, and previous mental health complaints. Methods Latent class growth modeling was used to identify distinct trajectories of PCBD, depression, and PTSD symptoms in people who lost loved ones in a plane disaster in 2014. Participants (N = 172) completed questionnaires for PCBD, depression, and PTSD at 11, 22, 31, and 42 months postdisaster. Associations among class membership and background and loss‐related variables, psychological support, and previous mental health complaints were examined using logistic regression analyses. Results Two PCBD classes emerged: mild (81.8%) and chronic (18.2%) PCBD. For both depression and PTSD, three classes emerged: mild (85.6% and 85.2%), recovered (8.2% and 4.4%), and chronic trajectory (6.2% and 10.3%). People assigned to the chronic PCBD, depression, or PTSD class were less highly educated than people assigned to the mild/recovered classes. Conclusions This is the first latent trajectory study that offers insights in individual differences in longitudinal symptom profiles of PCBD, depression, and PTSD in bereaved people. We found support for differential trajectories and predictors across the outcomes. - Depression and Anxiety, EarlyView.
  

  October 19, 2018   doi: 10.1002/da.22850   open full text
• Aerobic exercise for adult patients with major depressive disorder in mental health services: A systematic review and meta‐analysis.
  Ioannis D. Morres, Antonis Hatzigeorgiadis, Afroditi Stathi, Nikos Comoutos, Chantal Arpin‐Cribbie, Charalampos Krommidas, Yannis Theodorakis.
  Depression and Anxiety. October 18, 2018
  --- - |2 Abstract Although exercise is associated with depression relief, the effects of aerobic exercise (AE) interventions on clinically depressed adult patients have not been clearly supported. The purpose of this meta‐analysis was to examine the antidepressant effects of AE versus nonexercise comparators exclusively for depressed adults (18–65 years) recruited through mental health services with a referral or clinical diagnosis of major depression. Eleven e‐databases and bibliographies of 19 systematic reviews were searched for relevant randomized controlled clinical trials. A random effects meta‐analysis (Hedges’ g criterion) was employed for pooling postintervention scores of depression. Heterogeneity and publication bias were examined. Studies were coded considering characteristics of participants and interventions, outcomes and comparisons made, and study design; accordingly, sensitivity and subgroup analyses were calculated. Across 11 eligible trials (13 comparisons) involving 455 patients, AE was delivered on average for 45 min, at moderate intensity, three times/week, for 9.2 weeks and showed a significantly large overall antidepressant effect (g = –0.79, 95% confidence interval = –1.01, –0.57, P < 0.00) with low and nonstatistically significant heterogeneity (I2 = 21%). No publication bias was found. Sensitivity analyses revealed large or moderate to large antidepressant effects for AE (I2 ≤ 30%) among trials with lower risk of bias, trials with short‐term interventions (up to 4 weeks), and trials involving individual preferences for exercise. Subgroup analyses revealed comparable effects for AE across various settings and delivery formats, and in both outpatients and inpatients regardless symptom severity. Notwithstanding the small number of trials reviewed, AE emerged as an effective antidepressant intervention. - Depression and Anxiety, EarlyView.
  

  October 18, 2018   doi: 10.1002/da.22842   open full text
• Pathways from parental mental disorders to offspring's work disability due to depressive or anxiety disorders in early adulthood—The 1987 Finnish Birth Cohort.
  Jaana I. Halonen, Marko Merikukka, Mika Gissler, Martta Kerkelä, Marianna Virtanen, Tiina Ristikari, Heikki Hiilamo, Tea Lallukka.
  Depression and Anxiety. October 17, 2018
  --- - |2+ Background Parental mental disorders have been shown to predict offspring's mental health problems. We examined whether pathways from parental mental disorders to offspring's psychiatric work disability in early adulthood are mediated through offspring's mental disorders and social disadvantage in adolescence. Methods Study population consisted of the 1987 Finnish Birth Cohort. Data on parents’ psychiatric care or work disability due to mental diagnosis between 1987 and 2000 and the cohort participants’ health and social factors between 2001 and 2005 were derived from administrative national registers. From 2006 through 2015, 52,182 cohort participants were followed for admittance of psychiatric work disability due to depressive or anxiety disorders. First, we applied a pathway analysis to examine the occurrence of each path. We then used mediation analysis to assess the proportion of association between parental mental disorders and work disability mediated by offspring's health and social disadvantage. Results The pathway model indicated that the association from parental mental disorders to offspring's work disability due to depressive or anxiety disorder is through mental disorders and social disadvantage in adolescence. Odds Ratio for the total effect of parental mental disorders on offspring's psychiatric work disability was 1.85 (95% confidence interval [CI] 1.46–2.34) in the model including offspring's mental disorders that mediated this association by 35%. Corresponding results were 1.86 (95% CI 1.47–2.35) and 28% for social disadvantage in adolescence. Conclusions These findings suggest that intergenerational determination of work disability due to mental disorders could be addressed by actions supporting mental health and social circumstances in adolescence. - Depression and Anxiety, EarlyView.
  

  October 17, 2018   doi: 10.1002/da.22847   open full text
• Examination of ataque de nervios and ataque de nervios like events in a diverse sample of adults with anxiety disorders.
  Ethan Moitra, Yovanska Duarte‐Velez, Roberto Lewis‐Fernández, Risa B. Weisberg, Martin B. Keller.
  Depression and Anxiety. October 17, 2018
  --- - |2+ Background Ataque de nervios (ataque) represents a cultural syndrome of paroxysmic symptoms that is described as an expression of distress among Latinx (gender‐inclusive term for people of Latin‐American descent). Some ataques are symptomatically similar to DSM‐5‐defined panic attacks, but also may include acute anger, grief, suicidal/violent behavior, or dissociation, and can last for hours or even days. Ataques usually occur after stressors and can trigger the mobilization of social support networks. Although described as a cultural syndrome, two studies showed that ataque‐like events can occur in non‐Latinx individuals. However, neither of the previous studies examined these events in psychiatric samples and both were hindered by methodological shortcomings. Methods The present study examined lifetime prevalence of ataques and ataque‐like events in an ethnically/racially diverse sample of 245 adults with anxiety disorders to better understand acute reactions to stressors across cultures. Results Controlling for previously established correlates of ataque, results showed that Latinx were significantly more likely to report ever having an ataque (B = 1.41; P = 0.001; OR = 4.10 [95% CI: 1.72–9.80]), but events were reported by some non‐Latinx African Americans and Whites. Anxiety sensitivity was also a significant predictor. Across the three groups, minor differences were found in symptoms, severity, or precipitants of attacks. Conclusions Findings suggest that Latinx are more likely to experience ataques but that stressors can trigger similar symptoms in non‐Latinx. However, more research is needed to understand the meaning of these attacks within non‐Latinx groups as the explanations, connotations, and help‐seeking expectations regarding ataque are connected to Latinx cultures. - Depression and Anxiety, EarlyView.
  

  October 17, 2018   doi: 10.1002/da.22853   open full text
• Exercise and mental health literacy in an Australian adult population.
  Robert Stanton, Amanda Rebar, Simon Rosenbaum.
  Depression and Anxiety. October 17, 2018
  --- - |2+ Abstract Background Exercise is a well‐established treatment for depression, and its use in clinical care is supported by consumers and clinicians. However, whether public health messages regarding the benefits of exercise for depression have translated to public knowledge remains unknown. This study aims to examine the community's mental health literacy, and views regarding exercise delivery for people with depression. Methods A vignette was presented as part of the telephone‐based 2017 National Social Survey (n = 1,265). Interviewees identified what (if anything) was wrong with the person described, who they should seek help from, whether exercise might be beneficial, and how exercise should be delivered for the person described in the vignette. Results are reported using descriptive statistics. Results From 1,265 respondents (response rate = 24%, n = 598 males, mean age 54.7 years [range 18–101]), almost two‐thirds correctly identified the condition described in the vignette as depression. There was widespread support for seeking help from a general practitioner. Exercise was well supported in the treatment of the person described in the vignette, with general practitioners and accredited exercise physiologists highlighted as persons to consult regarding exercise. Views regarding the type of program were consistent with current best practice recommendations. Conclusions Australian adults demonstrate a high level of exercise and mental health literacy. The high level of support for accredited exercise physiologists is evidence of the effectiveness of health promotion campaigns from peak exercise professional agencies. - Depression and Anxiety, EarlyView.
  

  October 17, 2018   doi: 10.1002/da.22851   open full text
• Determinants of suboptimal medication adherence in patients with a major depressive episode.
  Carolina Baeza‐Velasco, Emilie Olié, Séverine Béziat, Sébastien Guillaume, Philippe Courtet.
  Depression and Anxiety. October 17, 2018
  --- - |2+ Background Major Depression (MD) is often a chronic condition requiring a long‐term pharmacologic treatment. Despite the efficacy of antidepressants, the medication adherence in those affected is usually very poor. In this scenario, further research concerning drivers of suboptimal adherence is needed. We aimed to explore medication adherence in patients with a MD episode, and to identify sociodemographic, clinical (psychiatric antecedents, comorbidities, medication, pain, and medication side effects), and psychosocial factors (negative life events, childhood trauma, and attitudes to medication) related to adherence status. Method The Medication Adherence Rating Scale (MARS) was completed by 370 patients at hospital admission. Participants were divided into groups of optimal and suboptimal adherence based on the medication adherence behavior score (MARS's factor 1), and were compared with respect to the study variables. Results Twenty‐nine percent of participants (n = 107) were found to be optimally adherents to their medication (score = 4/4). Compared to optimally adherents, suboptimally adherents (71%) presented a significantly higher depression severity, more psychiatric hospitalizations, suicidal ideation, physical pain, negative medication side effects, and antecedents of emotional maltreatment. Suboptimally adherents also had less favorable attitudes toward medication and were less in a relationship than optimally adherents. Multivariate analyses showed that depression severity, suicidal ideation, and physical pain increase the probability of belonging to the suboptimal adherent group. Conclusion These results suggest a vicious circle in which more vulnerable patients are less adherent to medication, which could worsen the clinical picture maintaining, in turn, low adherence. More efforts are needed to develop interventions aiming to improve medication adherence in MD patients. - Depression and Anxiety, EarlyView.
  

  October 17, 2018   doi: 10.1002/da.22852   open full text
• Validity of the DSM‐5 anxious distress specifier for major depressive disorder.
  Mark Zimmerman, Jacob Martin, Patrick McGonigal, Lauren Harris, Sophie Kerr, Caroline Balling, Reina Kiefer, Kasey Stanton, Kristy Dalrymple.
  Depression and Anxiety. October 12, 2018
  --- - |2+ Background DSM‐5 introduced the anxious distress specifier in recognition of the clinical significance of anxiety in depressed patients. Recent studies that supported the validity of the specifier did not use measures that were designed to assess the criteria of the specifier but instead approximated the DSM‐5 criteria from scales that were part of an existing data base. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the validity of the specifier diagnosed with a semistructured interview. Methods Two hundred sixty patients with a principal diagnosis of major depressive disorder were evaluated with semistructured diagnostic interviews. The patients were rated on clinician rating scales of depression, anxiety and irritability, and completed self‐report measures. Results Approximately three‐quarters of the depressed patients met the criteria for the anxious distress specifier. Patients with anxious distress had a higher frequency of anxiety disorders, particularly panic disorder and generalized anxiety disorder, as well as higher scores on measures of anxiety, depression, and anger. The patients meeting the anxious distress subtype reported higher rates of drug use disorders, poorer functioning during the week before the evaluation, and poorer coping ability compared to the patients who did not meet the anxious distress specifier. Moreover, anxious distress was associated with poorer functioning and coping after controlling for the presence of an anxiety disorder. Conclusions The results of the present study indicate that anxious distress is common in depressed patients and support the validity of the DSM‐5 anxious distress specifier. - Depression and Anxiety, EarlyView.
  

  October 12, 2018   doi: 10.1002/da.22837   open full text
• Heart rate variability as a biomarker of anxious depression response to antidepressant medication.
  Katharina Kircanski, Leanne M. Williams, Ian H. Gotlib.
  Depression and Anxiety. October 12, 2018
  --- - |2+ Background There is a need to identify biomarkers of treatment outcomes for major depressive disorder (MDD) that can be disseminated. We investigated the predictive utility of pretreatment heart rate variability (HRV) for outcomes of antidepressant medication in MDD, with pretreatment anxious depression as a hypothesized moderator of HRV effects. Methods A large, randomized, multicenter practical trial (International Study to Predict Optimized Treatment in Depression) in patients with current nonpsychotic MDD (N = 1,008; 722 completers) had three arms: escitalopram, sertraline, and venlafaxine‐extended release. At pretreatment, patients were defined as having anxious (N = 309) versus nonanxious (N = 413) depression and their resting high‐frequency HRV (root mean square of successive differences) was assessed. Patients’ usual treating clinicians managed medication. At 8 weeks, primary outcomes were clinician‐rated depressive symptom response and remission; secondary outcomes were self‐reported response and remission. Results Pretreatment HRV predicted antidepressant outcomes as a function of anxious versus nonanxious depression. In anxious depression, patients with higher HRV had better outcomes, whereas patients with lower HRV had poorer outcomes. In nonanxious depression, patients with lower HRV had better outcomes, whereas patients with higher HRV had poorer outcomes. Some simple effects were not significant. Results did not differ by treatment arm and remained significant when controlling for important covariates. Conclusions These findings inform a precision medicine approach in which clinical and biological assessments may be integrated to facilitate treatment outcome prediction. Knowing about HRV may help determine which patients with anxious depression could benefit from antidepressants and which patients may require a different treatment approach. - Depression and Anxiety, EarlyView.
  

  October 12, 2018   doi: 10.1002/da.22843   open full text
• Differences between chronic and nonchronic depression: Systematic review and implications for treatment.
  Stephan Köhler, Sophia Chrysanthou, Anne Guhn, Philipp Sterzer.
  Depression and Anxiety. October 09, 2018
  --- - |2+ Background There is still uncertainty if and to what extent chronic depression (CD) presents with specific features especially in contrast to the nonchronic course of major depressive disorder (non‐CD). This systematic review aims to summarize the existing literature regarding sociodemographic factors, psychopathology, and course of disease in patients with CD in comparison to patients with non‐CD. Methods A structured database search (MEDLINE, PsycINFO, Web of Science, CENTRAL) was performed. All studies comparing CD with non‐CD patients were included. Twenty‐eight studies, including cohort studies, cross‐sectional studies, and observational studies, were identified in which both subgroups were diagnosed according to DSM‐IV or DSM‐5, respectively. Primary outcome were group comparisons focused on sociodemographic factors, childhood adversity, onset of the disorder, comorbidities, severity and course of the depressive symptoms, and specific psychopathology. Results Patients with CD had an earlier onset of depressive symptoms, higher rates of psychiatric comorbidities, and a complicated treatment course (e.g., higher rates of suicidality) compared to non‐CD. We also found some evidence for specific features in the psychopathology of CD patients (submissive and hostile interpersonal styles) in contrast to non‐CD patients. Results were inconsistent with regard to childhood maltreatment. No differences were found regarding the severity of depressive symptoms and most sociodemographic factors. Conclusion Despite some inconsistencies, the results of this review verified important differences between CD and non‐CD. However, future research is needed to characterize especially the specific psychopathology of CD in comparison to non‐CD patients to develop more tailored treatment strategies. - Depression and Anxiety, EarlyView.
  

  October 09, 2018   doi: 10.1002/da.22835   open full text
• Issue Information.
  
  Depression and Anxiety. October 02, 2018
  --- - - Depression and Anxiety, Volume 35, Issue 10, Page 907-913, October 2018.
  

  October 02, 2018   doi: 10.1002/da.22846   open full text
• Smaller hippocampal CA1 subfield volume in posttraumatic stress disorder.
  Lyon W. Chen, Delin Sun, Sarah L. Davis, Courtney C. Haswell, Emily L. Dennis, Chelsea A. Swanson, Christopher D. Whelan, Boris Gutman, Neda Jahanshad, Juan Eugenio Iglesias, Paul Thompson, Mid‐Atlantic MIRECC Workgroup, H. Ryan Wagner, Philipp Saemann, Kevin S. LaBar, Rajendra A. Morey.
  Depression and Anxiety. September 26, 2018
  --- - |2+ Background Smaller hippocampal volume in patients with posttraumatic stress disorder (PTSD) represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD‐associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features. Methods Case‐control cross‐sectional studies of U.S. military veterans (n = 282) from the Iraq and Afghanistan era were grouped into PTSD (n = 142) and trauma‐exposed controls (n = 140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3 T. Segmentation with FreeSurfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, DG, fimbria, fissure, hippocampus‐amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model. Results Significantly lower subfield volumes were associated with PTSD in left CA1 (P = 0.01; d = 0.21; uncorrected), CA3 (P = 0.04; d = 0.08; uncorrected), and right CA3 (P = 0.02; d = 0.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. A trend level association of L‐CA1 with PTSD (F4, 221 = 3.32, P = 0.07) is present and the other subfield findings are nonsignificant if ipsilateral whole hippocampal volume is not included as a covariate. PTSD‐associated differences in global hippocampal shape were nonsignificant. Conclusions The present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety‐like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories. - Depression and Anxiety, EarlyView.
  

  September 26, 2018   doi: 10.1002/da.22833   open full text
• Intrinsic functional and structural connectivity of emotion regulation networks in obsessive‐compulsive disorder.
  Maria Picó‐Pérez, Jonathan Ipser, Paul Taylor, Pino Alonso, Clara López‐Solà, Eva Real, Cinto Segalàs, Annerine Roos, José M. Menchón, Dan J. Stein, Carles Soriano‐Mas.
  Depression and Anxiety. September 25, 2018
  --- - |2 Abstract Despite emotion regulation being altered in patients with obsessive‐compulsive disorder (OCD), no studies have investigated its relation to multimodal amygdala connectivity. We compared corticolimbic functional and structural connectivity between OCD patients and healthy controls (HCs), and correlated this with the dispositional use of emotion regulation strategies and with OCD severity. OCD patients (n = 73) and HCs (n = 42) were assessed for suppression and reappraisal strategies using the Emotion Regulation Questionnaire (ERQ) and for OCD severity using the Yale‐Brown Obsessive‐Compulsive Scale. Resting‐state functional magnetic resonance imaging (rs‐fMRI) connectivity maps were generated using subject‐specific left amygdala (LA) and right amygdala (RA) masks. We identified between‐group differences in amygdala whole‐brain connectivity, and evaluated the moderating effect of ERQ strategies. Significant regions and amygdala seeds were used as targets in probabilistic tractography analysis. Patients scored higher in suppression and lower in reappraisal. We observed higher rs‐fMRI RA–right postcentral gyrus (PCG) connectivity in HC, and in patients this was correlated with symptom severity. Reappraisal scores were associated with higher negative LA–left insula connectivity in HC, and suppression scores were negatively associated with LA–precuneus and angular gyri connectivity in OCD. Structurally, patients showed higher mean diffusivity in tracts connecting the amygdala with the other targets. RA–PCG connectivity is diminished in patients, while disrupted emotion regulation is related to altered amygdala connectivity with the insula and posterior brain regions. Our results are the first showing, from a multimodal perspective, the association between amygdala connectivity and specific emotional processing domains, emphasizing the importance of amygdala connectivity in OCD pathophysiology. - Depression and Anxiety, EarlyView.
  

  September 25, 2018   doi: 10.1002/da.22845   open full text
• Shortening self‐report mental health symptom measures through optimal test assembly methods: Development and validation of the Patient Health Questionnaire‐Depression‐4.
  Miyabi Ishihara, Daphna Harel, Brooke Levis, Alexander W. Levis, Kira E. Riehm, Nazanin Saadat, Marleine Azar, Danielle B. Rice, Tatiana A. Sanchez, Matthew J. Chiovitti, Pim Cuijpers, Simon Gilbody, John P. A. Ioannidis, Lorie A. Kloda, Dean McMillan, Scott B. Patten, Ian Shrier, Bruce Arroll, Charles H. Bombardier, Peter Butterworth, Gregory Carter, Kerrie Clover, Yeates Conwell, Felicity Goodyear‐Smith, Catherine G. Greeno, John Hambridge, Patricia A. Harrison, Marie Hudson, Nathalie Jetté, Kim M. Kiely, Anthony McGuire, Brian W. Pence, Alasdair G. Rooney, Abbey Sidebottom, Adam Simning, Alyna Turner, Jennifer White, Mary A. Whooley, Kirsty Winkley, Andrea Benedetti, Brett D. Thombs.
  Depression and Anxiety. September 20, 2018
  --- - |2+ Background The objective of this study was to develop and validate a short form of the Patient Health Questionnaire‐9 (PHQ‐9), a self‐report questionnaire for assessing depressive symptomatology, using objective criteria. Methods Responses on the PHQ‐9 were obtained from 7,850 English‐speaking participants enrolled in 20 primary diagnostic test accuracy studies. PHQ unidimensionality was verified using confirmatory factor analysis, and an item response theory model was fit. Optimal test assembly (OTA) methods identified a maximally precise short form for each possible length between one and eight items, including and excluding the ninth item. The final short form was selected based on prespecified validity, reliability, and diagnostic accuracy criteria. Results A four‐item short form of the PHQ (PHQ‐Dep‐4) was selected. The PHQ‐Dep‐4 had a Cronbach's alpha of 0.805. Sensitivity and specificity of the PHQ‐Dep‐4 were 0.788 and 0.837, respectively, and were statistically equivalent to the PHQ‐9 (sensitivity = 0.761, specificity = 0.866). The correlation of total scores with the full PHQ‐9 was high (r = 0.919). Conclusion The PHQ‐Dep‐4 is a valid short form with minimal loss of information of scores when compared to the full‐length PHQ‐9. Although OTA methods have been used to shorten patient‐reported outcome measures based on objective, prespecified criteria, further studies are required to validate this general procedure for broader use in health research. Furthermore, due to unexamined heterogeneity, there is a need to replicate the results of this study in different patient populations. - Depression and Anxiety, EarlyView.
  

  September 20, 2018   doi: 10.1002/da.22841   open full text
• Social cognitive abilities predict psychosocial dysfunction in major depressive disorder.
  Matthew J. Knight, Bernhard T. Baune.
  Depression and Anxiety. September 13, 2018
  --- - |2+ Background Major depressive disorder (MDD) is associated with social cognitive deficits (e.g., poor affect recognition and impaired theory of mind). However, the contribution of social cognitive issues to psychosocial dysfunction in MDD (e.g., occupational functioning and interpersonal relationships) has not been investigated. The current study evaluated the relationship between specific social cognitive domains (e.g., prosody interpretation) and psychosocial dysfunction in subjects with lifetime MDD, as well as currently depressed, remitted, and healthy controls (HCs) subjects. Method Data were obtained from 213 participants in the Cognitive Function and mood study (CoFaMS), a cross‐sectional study of mood, social cognition, cold cognition, and psychosocial functioning in mood disorders. Participants’ (current MDD n = 42, remitted MDD n = 69, and HCs n = 102) social cognitive abilities were assessed using the Social Perception subtest of the Wechsler Adult Intelligence Scale, and psychosocial dysfunction was clinically evaluated with the Functioning Assessment Short Test (FAST). Results The results indicated that prosody interpretation, but not facial affect or meaning interpretation, was associated with psychosocial dysfunction in subjects with lifetime MDD, as well as remitted MDD subjects relative to HCs. In contrast, social cognition was not associated with functioning in participants with current MDD or in HCs. Conclusions These results suggest that the relationship between social cognition and psychosocial functioning differs between the acute and remitted stage of illness in MDD, and that prosody interpretation should be considered a treatment target in patients with residual psychosocial issues. - Depression and Anxiety, EarlyView.
  

  September 13, 2018   doi: 10.1002/da.22844   open full text
• Course and stability of cognitive and metacognitive beliefs in depression.
  Mirjam Faissner, Levente Kriston, Steffen Moritz, Lena Jelinek.
  Depression and Anxiety. September 12, 2018
  --- - |2 Abstract Maladaptive cognitive beliefs as measured by the Dysfunctional Attitudes Scale (DAS) increase vulnerability to depression. Maladaptive metacognitive beliefs as measured by the Metacognitive Questionnaire‐30 (MCQ‐30) are also thought to contribute to depression. However, the long‐term stability of metacognitive beliefs in depression has not yet been investigated. It is unclear whether metacognitive beliefs can add explanatory power to depression above and beyond maladaptive cognitive beliefs. The aim of the present study was to investigate the role and stability of cognitive and metacognitive maladaptive beliefs in depression. Eighty‐four patients with depression were assessed with the DAS, three subscales of the MCQ‐30 (positive metacognitive beliefs about worry and rumination [PB]; negative metacognitive beliefs about the uncontrollability of rumination [NB]; metacognitive beliefs concerning the need to control one's thoughts [NFC]), the Hamilton Depression Rating Scale, and the Beck Depression Inventory at baseline and were reassessed 3.5 years later. Analyses using a longitudinal latent growth model showed that change on the DAS and baseline scores and change on the MCQ‐30 (NB and NFC) significantly predicted change in self‐rated depressive symptoms over 3.5 years. However, the DAS explained more additional variance than the integration of the MCQ‐30 subscales. Subscales of the MCQ‐30 were more stable than the DAS. Although cognitive and metacognitive maladaptive beliefs were both predictors of depression, the DAS was a better predictor than the MCQ‐30 subscales. Nevertheless, because maladaptive metacognitive beliefs were more stable than maladaptive cognitive beliefs, they should be considered an important underlying vulnerability factor for depression. - Depression and Anxiety, EarlyView.
  

  September 12, 2018   doi: 10.1002/da.22834   open full text
• The association between anxiety, traumatic stress, and obsessive–compulsive disorders and chronic inflammation: A systematic review and meta‐analysis.
  Megan E. Renna, Mia S. O'Toole, Phillip E. Spaeth, Mats Lekander, Douglas S. Mennin.
  Depression and Anxiety. September 10, 2018
  --- - |2+ Background Anxiety is characterized by prolonged preparation for real or perceived threat. This may manifest both as psychological and physiological activation, ultimately leading to greater risk for poor health. Chronic inflammation may play an integral role in this relationship, given the influential role that it has in chronic illness. The aim of this meta‐analysis is to examine levels of chronic inflammation, measured by inflammatory cytokines and C‐reactive protein, in people with anxiety disorders, PTSD (posttraumatic stress disorder), or obsessive–compulsive disorder compared to healthy controls. Several moderating variables, including specific diagnosis and depression comorbidity, were also assessed. Methods Seventy six full‐text articles were screened for eligibility with 41 studies ultimately included in analysis. Results Results demonstrated a significant overall difference between healthy controls (HCs) and people with anxiety disorders in pro‐inflammatory cytokines (P = 0.013, Hedge's g = –0.39), which appears to be largely driven by interleukin‐1β (IL‐1β; P = 0.009, Hedge's g = –0.50), IL‐6 (P < 0.001, Hedge's g = –0.93), and tumor necrosis factor‐α (P = 0.030, Hedge's g = –0.56). Moderation analyses revealed a moderating effect of diagnosis (P = 0.050), as only individuals with PTSD demonstrated differences in inflammation between HCs (P = 0.004, Hedge's g = –0.68). Conclusions These data demonstrate the association between inflammatory dysregulation and diagnoses associated with chronic, impactful, and severe anxiety and provides insight into the way that anxiety, and in particular PTSD, is related to certain inflammatory markers. In doing so, these findings may provide an initial step in disentangling the relationship between anxiety and basic health processes. - Depression and Anxiety, EarlyView.
  

  September 10, 2018   doi: 10.1002/da.22790   open full text
• Moderating effect of comorbid anxiety disorders on treatment outcome in a randomized controlled psychotherapy trial in early‐onset persistently depressed outpatients.
  Nele Assmann, Elisabeth Schramm, Levente Kriston, Martin Hautzinger, Martin Härter, Ulrich Schweiger, Jan Philipp Klein.
  Depression and Anxiety. September 10, 2018
  --- - |2+ Background Persistent depressive disorder (PDD) is associated with high rates of comorbid psychiatric disorders, mostly anxiety disorders (ADs). Comorbid AD was found to be associated with poorer treatment outcome in PDD patients. The effect of comorbid AD on disorder‐specific treatment for PDD (Cognitive Behavioral Analysis System of Psychotherapy [CBASP]) has not been studied yet. Methods We analyzed whether the presence of a comorbid AD was moderating the effectiveness of disorder‐specific (CBASP) versus nonspecific psychotherapy (supportive therapy [SP]) on depressive symptoms (24‐item Hamilton Rating Scale for Depression [HRSD‐24]) in a sample of unmedicated early‐onset PDD outpatients (N = 268). Secondary outcomes were response and remission of depressive symptoms and the extent of interpersonal problems (Inventory of Interpersonal Problems [IIP‐64]). Results The superiority of CBASP over SP was significantly stronger in PDD patients with comorbid AD compared to patients without AD (in HRSD‐24 and IIP‐64). There was no significant moderation for remission or response of depressive symptoms. Discussion Our hypothesis of a moderating effect of comorbid AD was confirmed. The main limitation might be the exclusion criteria of our sample limiting the generalizability. The major strength is the systematic analysis of the effect of AD in treating early‐onset PDD with high quality of psychotherapy in both arms of this trial. Conclusion Patients suffering from PDD comorbid with AD might experience greater benefit when they are treated with specific as opposed to unspecific therapy. Analyzing subgroups of patients with PDD seems worthwhile to improve treatment effectiveness even within disorder‐specific treatment programms. - Depression and Anxiety, Volume 35, Issue 10, Page 1001-1008, October 2018.
  

  September 10, 2018   doi: 10.1002/da.22839   open full text
• Exposure‐based therapy changes amygdala and hippocampus resting‐state functional connectivity in patients with posttraumatic stress disorder.
  Xi Zhu, Benjamin Suarez‐Jimenez, Amit Lazarov, Liat Helpman, Santiago Papini, Ari Lowell, Ariel Durosky, Martin A. Lindquist, John C. Markowitz, Franklin Schneier, Tor D. Wager, Yuval Neria.
  Depression and Anxiety. September 10, 2018
  --- - |2+ Background Recent research suggests that posttraumatic stress disorder (PTSD) is associated with altered amygdala and hippocampal resting‐state functional connectivity (rsFC). However, less research has examined whether Prolonged Exposure (PE), a first line exposure‐based treatment for PTSD, has the potential to alter resting state neural networks. Methods A total of 24 patients with PTSD and 26 matched trauma‐exposed healthy controls (TEHCs) underwent resting‐state functional magnetic resonance imaging (fMRI) at baseline. PTSD patients were scanned a second time after completing 10‐session PE in which patients narrated a detailed trauma account (imaginal exposure) and confronted trauma reminders (in vivo exposure) to extinguish trauma‐related fear responses. TEHC were scanned again following a 10‐week waiting period. Seed regions of interest (ROIs) included centromedial amygdala (CMA), basolateral amygdala (BLA), and the hippocampus. Results Post‐ versus pretreatment comparisons indicated increased rsFC of the BLA and CMA with the orbitofrontal cortex (OFC), and hippocampus‐medial prefrontal cortex (mPFC) among patients with PTSD, but not among TEHC participants. Conclusions Enhanced amygdala and hippocampus rsFC with prefrontal cortical regions following PE could underlie improved capacity for inhibition and re‐evaluation of threat, and heightened memory encoding and retrieval ability, respectively. These findings encourage further investigation of this circuitry as a therapeutic target in PTSD. - Depression and Anxiety, Volume 35, Issue 10, Page 974-984, October 2018.
  

  September 10, 2018   doi: 10.1002/da.22816   open full text
• Posttraumatic stress disorder and cigarette smoking: A systematic review.
  Nathan T. Kearns, Emily Carl, Aliza T. Stein, Anka A. Vujanovic, Michael J. Zvolensky, Jasper A. J. Smits, Mark B. Powers.
  Depression and Anxiety. September 07, 2018
  --- - |2+ Background Previous reviews of the PTSD and cigarette smoking literature showed high PTSD‐smoking comorbidity and problematic smoking outcomes (Feldner et al., 2007, Clinical Psychology Review, 27, 14ica; Fu et al., 2007, Nicotine & Tobacco Research, 9, 1071ne & ). However, past reviews also noted several prominent gaps in the literature, including a lack of etiological work examining underlying mechanisms and research on specialized PTSD‐smoking treatments. The present review summarizes an extensive body of research conducted since the previous reviews targeting these areas of need. Methods Literature searches identified 66 empirical studies specific to smoking and PTSD. Results Smokers were approximately twice more likely to have PTSD than nonsmokers in the general population, and individuals with PTSD were approximately twice as likely to be current smokers. Smokers with PTSD evidenced more negative affect, trauma history, and comorbid psychiatric history, as well as quit attempts and higher relapse rates. PTSD symptoms were associated with expectations that smoking would reduce negative affect, which, in turn, was associated with increased smoking rate and nicotine dependence. Male sex was associated with nicotine dependence and PTSD avoidance, while the relationship between PTSD and smoking relapse due to withdrawal was stronger in females. Specialized, integrated PTSD and smoking cessation treatments showed promise in increasing quit success relative to standard care in randomized trials. Conclusions Rates of PTSD‐smoking co‐occurrence remain high. Notable gains have been made in relevant epidemiological and etiological research, although more work is needed in trauma‐specific subpopulations. Several promising specialized treatments for comorbid smoking–PTSD have been developed and empirically tested but require replication. - Depression and Anxiety, EarlyView.
  

  September 07, 2018   doi: 10.1002/da.22828   open full text
• Course of major depressive disorder after pregnancy and the postpartum period.
  Marlene P. Freeman, Lauren D. Claypoole, Vivien K. Burt, Alexandra Z. Sosinsky, Danna Moustafa, Olivia B. Noe, Laura J. Cheng, Lee S. Cohen.
  Depression and Anxiety. September 07, 2018
  --- - |2+ Background Maternal major depressive disorder (MDD) has an adverse effect on child development and increases risk for child psychopathology. It is paramount to understand the course of maternal depression during the childhood years particularly before, during, and after pregnancy. Objective To follow the course of MDD in women with prior histories of depression followed during an index pregnancy. Methods Subjects were women with histories of MDD who had participated in prior prospective, observational studies during pregnancy. In the follow‐up, participants completed a structured interview that addressed (1) the course of MDD since their index pregnancy, (2) new psychiatric diagnoses, and (3) the course of MDD and treatment across subsequent pregnancies. Results Out of 129 eligible women, 48.8% participated (N = 63) with an average/mean time of 12.9 years (SD = 1.9, 8.8–16.7) elapsed since participation in the prior pregnancy studies. Although approximately one third reported sustained remission from MDD since the pregnancy during which they had been originally followed, of the remaining two thirds of women who reported subsequent depressive episodes, almost one fifth (∼12% of the total sample) endorsed depression more than 50% of the time following their index pregnancy. A total of 6.3% of the women with previous validated diagnoses of MDD reported new diagnoses of bipolar disorder. Women reported similar treatment choices regarding the use of antidepressants during pregnancies subsequent to the one followed in the previous study. Conclusion Women with MDD experienced high rates of recurrent depression across the childbearing years. This represents a critical variable for clinical care and research. - Depression and Anxiety, EarlyView.
  

  September 07, 2018   doi: 10.1002/da.22836   open full text
• Patterns and factors associated with low adherence to psychotropic medications during pregnancy—A cross‐sectional, multinational web‐based study.
  
  Depression and Anxiety. September 07, 2018
  --- - - Depression and Anxiety, Volume 35, Issue 10, Page 1009-1009, October 2018.
  

  September 07, 2018   doi: 10.1002/da.22838   open full text
• Response rate profiles for major depressive disorder: Characterizing early response and longitudinal nonresponse.
  Mary E. Kelley, Boadie W. Dunlop, Charles B. Nemeroff, Adriana Lori, Tania Carrillo‐Roa, Elisabeth B. Binder, Michael H. Kutner, Vivianne Aponte Rivera, W. Edward Craighead, Helen S. Mayberg.
  Depression and Anxiety. September 07, 2018
  --- - |2+ Background Definition of response is critical when seeking to establish valid predictors of treatment success. However, response at the end of study or endpoint only provides one view of the overall clinical picture that is relevant in testing for predictors. The current study employed a classification technique designed to group subjects based on their rate of change over time, while simultaneously addressing the issue of controlling for baseline severity. Methods A set of latent class trajectory analyses, incorporating baseline level of symptoms, were performed on a sample of 344 depressed patients from a clinical trial evaluating the efficacy of cognitive behavior therapy and two antidepressant medications (escitalopram and duloxetine) in patients with major depressive disorder. Results Although very few demographic and illness‐related features were associated with response rate profiles, the aggregated effect of candidate genetic variants previously identified in large pharmacogenetic studies and meta‐analyses showed a significant association with early remission as well as nonresponse. These same genetic scores showed a less compelling relationship with endpoint response categories. In addition, consistent nonresponse throughout the study treatment period was shown to occur in different subjects than endpoint nonresponse, which was verified by follow‐up augmentation treatment outcomes. Conclusions When defining groups based on the rate of change, controlling for baseline depression severity may help to identify the clinically relevant distinctions of early response on one end and consistent nonresponse on the other. - Depression and Anxiety, Volume 35, Issue 10, Page 992-1000, October 2018.
  

  September 07, 2018   doi: 10.1002/da.22832   open full text
• Comparative responsiveness of generic versus disorder‐specific instruments for depression: An assessment in three longitudinal datasets.
  Edwin Beurs, Ellen Vissers, Robert Schoevers, Ingrid V. E. Carlier, Albert M. Hemert, Ybe Meesters.
  Depression and Anxiety. September 06, 2018
  --- - |2+ Background Routine outcome monitoring (ROM) may enhance individual treatment and is also advocated as a means to compare the outcome of different treatment programs or providers. There is debate on the optimal instruments to be used for these separate tasks. Methods Three sets with longitudinal data from ROM were analyzed with correlational analysis and repeated measures ANOVAs, allowing for a head‐to‐head comparison of measures regarding their sensitivity to detect change. The responsiveness of three disorder‐specific instruments, the Beck Depression Inventory, the Inventory of Depressive Symptoms, and the Mood and Anxiety Symptoms Questionnaire, was compared to three generic instruments, the Symptom Checklist (SCL‐90), the Outcome Questionnaire (OQ‐45), and the Brief Symptom Inventory, respectively. Results In two of the three datasets, disorder‐specific measures were more responsive compared to the total score on generic instruments. Subscale scores for depression embedded within generic instruments are second best and almost match disorder‐specific scales in responsiveness. No evidence of a desynchronous response on outcome measures was found. Limitations The present study compares measures head‐to‐had, and responsiveness is not assessed against an external criterion, such as clinical recovery. Discussion Disorder‐specific measures yield the most precise assessment for individual treatment and are recommended for clinical use. Generic measures may allow for comparisons across diagnostic groups and their embedded subscales approach the responsiveness of disorder‐specific measures. - Depression and Anxiety, EarlyView.
  

  September 06, 2018   doi: 10.1002/da.22809   open full text
• The prevalence and predictors of mental health diagnoses and suicide among U.S. college students: Implications for addressing disparities in service use.
  Cindy H. Liu, Courtney Stevens, Sylvia H.M. Wong, Miwa Yasui, Justin A. Chen.
  Depression and Anxiety. September 06, 2018
  --- - |2+ Background The college years represent a period of increased vulnerability for a wide range of mental health (MH) challenges. The onset of common psychiatric conditions occurs during this period of development. Increases in depression, anxiety, and suicidality among U.S. college students have been observed. This study identified prevalence and correlates of MH diagnoses and suicidality in a recent sample of U.S. college students. Methods The Spring 2015 American College Health Association‐National College Health Assessment (ACHA‐NCHA) survey assessed MH diagnoses and suicidality from U.S. undergraduate students (n = 67,308) across 108 institutions. Results Stress was strongly associated with a greater likelihood of suicide attempts and MH diagnoses, even among students reporting 1–2 stressful events (OR [odds ratio] range 1.6–2.6, CI [confidence interval] = 1.2–3.2). Bisexual students were more likely to report MH diagnoses and suicidality, compared to heterosexual and gay/lesbian students (OR range 1.5–3.9, CI = 1.8–4.3), with over half engaging in suicidal ideation and self‐harm, and over a quarter reporting suicide attempts. Transgender students reported a higher rate of MH diagnoses and suicidality relative to females (OR range 1.9–2.4, CI = 1.1–3.4). Racial/ethnic minority students were generally less likely to report MH diagnoses relative to Whites, although the likelihood for suicidality was mixed. Conclusions The high rate of multiple stress exposures among the U.S. college population and the high impacts of stress on MH and suicidality point to an urgent need for service utilization strategies, especially among racial/ethnic, sexual, or gender minorities. Campuses must consider student experiences to mitigate stress during this developmental period. - Depression and Anxiety, EarlyView.
  

  September 06, 2018   doi: 10.1002/da.22830   open full text
• Progesterone and plasma metabolites in women with and in those without premenstrual dysphoric disorder.
  Arianna Di Florio, Danny Alexander, Peter J. Schmidt, David R. Rubinow.
  Depression and Anxiety. September 05, 2018
  --- - |2+ Background The molecular mechanisms underpinning the progesterone‐triggering mood symptoms in women with premenstrual dysphoric disorder (PMDD) are unknown. Cell metabolism is a potential source of variability. Very little is known about the effect of progesterone sensitivity on the metabolome. In this study, we aimed to characterize the effects of progesterone on the global metabolic profile and explore the differences between women with PMDD and controls. Methods Plasma was obtained from 12 women with prospectively confirmed PMDD and 25 controls under two hormone conditions: (1) gonadal suppression induced by leuprolide acetate (3.75 mg IM monthly) and (2) add‐back phase with leuprolide and progesterone (200 mg twice daily by vaginal suppository). The global metabolic profile was obtained using liquid and gas chromatography followed by mass spectrometry. Differences between groups and time points were tested using repeated measures analysis of variance. The false discovery rate was calculated to account for multiple testing. Results Amino acids and their derivatives represented 78% (28/36) of the known compounds that were found in significantly lower plasma concentrations after progesterone administration than during gonadal suppression. The concentration of tyrosine was nominally significantly decreased after progesterone add‐back in controls, but not in cases (P = 0.02). Conclusion Plasma levels of some amino acids are decreased in response to progesterone. Albeit preliminary, evidence further suggests that progesterone has a different effect on the metabolic profiles of women with PMDD compared to controls. Further research is needed to replicate our findings in a larger sample and to identify the unknown compounds, especially those differentially expressed. - Depression and Anxiety, EarlyView.
  

  September 05, 2018   doi: 10.1002/da.22827   open full text
• Is assessment of depression equivalent for migrants of different cultural backgrounds? Results from the German population‐based Gutenberg Health Study (GHS).
  Ana Nanette Tibubos, Manfred E. Beutel, Andreas Schulz, Eva M. Klein, Elmar Brähler, Matthias Michal, Thomas Münzel, Philipp S. Wild, Karl Lackner, Jochem König, Norbert Pfeiffer, Jörg Wiltink.
  Depression and Anxiety. August 29, 2018
  --- - |2+ Background Bearing in mind the multicultural background of a national population, little is known about the measurement invariance across different cultures or ethnicities of frequently used screeners for depression. For this reason, the main objective of the current study is to assess the measurement invariance of the Patient Health Questionnaire (PHQ‐9) across groups with different migration backgrounds. Methods We provided psychometric analyses (descriptive statistics at item and scale level, reliability analysis, exploratory [EFA] and confirmatory factor analyses [CFA]) comparing a native population with first‐ and second‐generation migrants of the German population‐based Gutenberg Health Study with N = 13,973 participants completing the PHQ‐9. Furthermore, we conducted measurement invariance analyses among different groups of first‐generation migrants. Results Comparing the native population with first‐ and second‐generation migrants, a higher prevalence for mental distress was found for first generation. Although mean score patterns were similar for all groups, analyses of item loadings among first‐generation migrants yielded some variance in patterns pointing out that certain items have a distinct impact on depression for specific groups. With regard to the factorial validity for all groups, EFA and CFA provided evidence for the proposed one latent factor structure of the PHQ‐9. Depression assessed by the PHQ‐9 turned out to be equivalent from a psychometric perspective across different groups stratified by their migration background. Conclusions Overall, results of thorough scale and item analyses, especially multigroup confirmatory analyses, provided support that depression, assessed by the PHQ‐9, can be considered as psychometrically equivalent across all analyzed groups. - Depression and Anxiety, EarlyView.
  

  August 29, 2018   doi: 10.1002/da.22831   open full text
• Malaise with praise: A narrative review of 10 years of research on the concept of Fear of Positive Evaluation in social anxiety.
  Julia Reichenberger, Jens Blechert.
  Depression and Anxiety. August 24, 2018
  --- - |2 Abstract Social anxiety is characterized by a fear of being negatively evaluated by others (i.e., Fear of Negative Evaluation [FNE]). In 2008, Weeks, Heimberg, and Rodebaugh proposed Fear of Positive Evaluation (FPE) as a second cognitive component in social anxiety. The article presents an overview of FPE, its psycho‐evolutionary theoretical foundation and assessment by the Fear of Positive Evaluation Scale as well as relevant psychometric research on demographic characteristics. The relationship of FPE with a wide range of established dimensions from clinical, personality, and social psychology (i.e., self‐esteem, perfectionism, or quality of life) will be reviewed. The role of FPE for psychological comorbidities such as other anxiety disorders, depression, eating, and substance use disorders as well as for treatment of social anxiety will be discussed. Future research might address questions of causality of FPE relative to related constructs, further data on psychometric properties, as well as on its independence from FNE in longitudinal studies. In sum, FPE seems to be a valid and reliable construct that explains cognitions, emotions, and behavior related to social anxiety at subclinical and clinical levels and therefore enriches the psychometric repertoire in the fields of social psychology, personality, and clinical psychology. - Depression and Anxiety, EarlyView.
  

  August 24, 2018   doi: 10.1002/da.22808   open full text
• Long‐term treatment gains of a brief exposure‐based treatment for PTSD.
  Johanna Thompson‐Hollands, Brian P. Marx, Daniel J. Lee, Patricia A. Resick, Denise M. Sloan.
  Depression and Anxiety. August 24, 2018
  --- - |2+ Background Written exposure therapy (WET) is a 5‐session PTSD treatment that may address barriers in treatment for posttraumatic stress disorder (PTSD) given its brevity and tolerability. A recent study found outcomes for WET were non‐inferior to outcomes from Cognitive Processing Therapy (CPT) through 36 weeks from first treatment session (Sloan, Marx, Lee, & Resick, 2018); the current study examined whether treatment gains were maintained through 60 weeks from first session, and also evaluated both treatments’ effect on depressive symptoms. Methods The study enrolled 126 individuals with PTSD randomized to WET or CPT. Assessments were conducted at baseline and 6, 12, 24, 36, and 60 weeks following the first treatment session. PTSD diagnosis and symptom severity were determined via the Clinician Administered PTSD Scale for DSM‐5 (CAPS‐5), and depression symptoms were assessed using the Beck Depression Inventory‐2. Results WET remained non‐inferior to CPT through the 60 week assessment; the groups had a difference of less than 3 points in their total CAPS‐5 scores, and within‐condition effects on PTSD were large (WET d = 1.23; CPT d = 1.38). Both treatments significantly reduced depressive symptoms over the 60 week study, with the CPT group experiencing a more rapid decrease. The between‐condition effect of treatment on depression was small (d = .19). Conclusions WET is a treatment that is non‐inferior to CPT with regard to PTSD symptoms, with treatment effects that are long‐lasting. Additionally, both WET and CPT demonstrated substantial effects on depressive symptoms. WET should be considered a good option for PTSD treatment. - Depression and Anxiety, Volume 35, Issue 10, Page 985-991, October 2018.
  

  August 24, 2018   doi: 10.1002/da.22825   open full text
• Maternal depression alters stress and immune biomarkers in mother and child.
  Adi Ulmer‐Yaniv, Amir Djalovski, Avital Priel, Orna Zagoory‐Sharon, Ruth Feldman.
  Depression and Anxiety. August 22, 2018
  --- - |2+ Background Exposure to maternal depression bears long‐term negative consequences for children's well‐being. Yet, no study has tested the joint contribution of maternal and child's hypothalamic pituitary axis and immune systems in mediating the effects of maternal depression on child psychopathology. Methods We followed a birth cohort over‐represented for maternal depression from birth to 10 years (N = 125). At 10 years, mother and child's cortisol (CT) and secretory immunoglobulin A (s‐IgA), biomarkers of the stress and immune systems, were assayed, mother–child interaction observed, mothers and children underwent psychiatric diagnosis, and children's externalizing and internalizing symptoms reported. Results Depressed mothers had higher CT and s‐IgA levels and displayed more negative parenting, characterized by negative affect, intrusion, and criticism. Children of depressed mothers exhibited more Axis‐I disorders, higher s‐IgA levels, and greater social withdrawal. Structural equation modeling charted four paths by which maternal depression impacted child externalizing and internalizing symptoms: (a) increasing maternal CT, which linked with higher child CT and behavior problems; (b) augmenting maternal and child's immune response, which were associated with child symptoms; (c) enhancing negative parenting that predicted child social withdrawal and symptoms; and (d), via a combined endocrine‐immune pathway suppressing symptom formation. Conclusions Our findings, the first to test stress and immune biomarkers in depressed mothers and their children in relation to social behavior, describe mechanisms of endocrine synchrony in shaping children's stress response and immunity, advocate the need to follow the long‐term effects of maternal depression on children's health throughout life, and highlight maternal depression as an important public health concern. - Depression and Anxiety, EarlyView.
  

  August 22, 2018   doi: 10.1002/da.22818   open full text
• The accuracy of passive phone sensors in predicting daily mood.
  Abhishek Pratap, David C. Atkins, Brenna N. Renn, Michael J. Tanana, Sean D. Mooney, Joaquin A. Anguera, Patricia A. Areán.
  Depression and Anxiety. August 21, 2018
  --- - |2+ Background Smartphones provide a low‐cost and efficient means to collect population level data. Several small studies have shown promise in predicting mood variability from smartphone‐based sensor and usage data, but have not been generalized to nationally recruited samples. This study used passive smartphone data, demographic characteristics, and baseline depressive symptoms to predict prospective daily mood. Method Daily phone usage data were collected passively from 271 Android phone users participating in a fully remote randomized controlled trial of depression treatment (BRIGHTEN). Participants completed daily Patient Health Questionnaire‐2. A machine learning approach was used to predict daily mood for the entire sample and individual participants. Results Sample‐wide estimates showed a marginally significant association between physical mobility and self‐reported daily mood (B = –0.04, P < 0.05), but the predictive models performed poorly for the sample as a whole (median R2 ∼ 0). Focusing on individuals, 13.9% of participants showed significant association (FDR < 0.10) between a passive feature and daily mood. Personalized models combining features provided better prediction performance (median area under the curve [AUC] > 0.50) for 80.6% of participants and very strong prediction in a subset (median AUC > 0.80) for 11.8% of participants. Conclusions Passive smartphone data with current features may not be suited for predicting daily mood at a population level because of the high degree of intra‐ and interindividual variation in phone usage patterns and daily mood ratings. Personalized models show encouraging early signs for predicting an individual's mood state changes, with GPS‐derived mobility being the top most important feature in the present sample. - Depression and Anxiety, EarlyView.
  

  August 21, 2018   doi: 10.1002/da.22822   open full text
• Interplay between RGS2 and childhood adversities in predicting anxiety and depressive disorders: Findings from a general population sample.
  Eva Asselmann, Johannes Hertel, Carsten‐Oliver Schmidt, Georg Homuth, Matthias Nauck, Katja Beesdo‐Baum, Hans‐Jörgen Grabe, Christiane A. Pané‐Farré.
  Depression and Anxiety. August 14, 2018
  --- - |2+ Background It remains unresolved whether childhood adversities interact with genetic variation in regulator of G‐protein signaling 2 (RGS2) rs4606 in predicting various anxiety and depressive disorders and whether diagnostic specificity exists in these interactions. Methods The genotype of RGS2 rs4606 was determined for N = 2,263 adults with European ancestry from the Study of Health in Pomerania. Lifetime anxiety and depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were assessed with the Munich Composite International Diagnostic Interview (DIA‐X/M‐CIDI). Childhood adversities were assessed with the Childhood Trauma Questionnaire (CTQ, when participants were aged 29–89). Results Logistic regressions adjusted for sex and age revealed that rs4606 interacted with total childhood adversity in predicting each diagnostic outcome except for panic disorder and generalized anxiety disorder, uncorrected and corrected for multiple testing (odds ratio [OR] = 1.06–1.16). That is, carriers of the GG (vs. CC/CG) genotype were at decreased risk for anxiety and/or depression in the presence of low, but at increased risk in the presence of high total childhood adversity. Respective gene–environment (G × E) interactions were found for (a) comorbid anxiety and depressive disorders (OR = 1.13), but neither pure anxiety nor pure depressive disorders and (b) pure/temporally primary anxiety disorders (OR = 1.07), but not pure/temporally primary depressive disorders. The G × E interaction remained associated with depressive disorders after introducing pure/temporally primary anxiety disorders as additional predictor (OR = 1.09). Conclusions rs4606 alters the risk of developing a range of anxiety but also depressive disorders after childhood adversities. A complex risk pattern of genotype, environmental factors, and preexisting anxiety contributes to subsequent depression development. - Depression and Anxiety, EarlyView.
  

  August 14, 2018   doi: 10.1002/da.22812   open full text
• Anhedonia and suicidal thoughts and behaviors in psychiatric outpatients: The role of acuity.
  Mariah Hawes, Igor Galynker, Shira Barzilay, Zimri S. Yaseen.
  Depression and Anxiety. August 14, 2018
  --- - |2+ Background Anhedonia—impairment related to the experience of pleasure—has been identified as a potential risk factor for suicide, with some mixed findings. The current study sought to clarify the role of acuity of anhedonia in the relationship between anhedonia and suicidal thoughts and behaviors by comparing acutely and chronically anhedonic subjects on severity of suicidal ideation (SI) and suicide attempt (SA) history. Methods Psychiatric outpatients (N = 395) were administered the Columbia Suicide Severity Rating Scale, the Beck Scale for Suicidal Ideation and a modified version of the Snaith–Hamilton Pleasure Scale (SHPS); SI measures were readministered at a 1‐month follow‐up (N = 289, 73%). Participants were classified as acutely anhedonic, chronically anhedonic and nonanhedonic based on their responses to the SHPS at initial assessment. Results Controlling for symptoms of anxiety and depression, acute anhedonia was cross‐sectionally and prospectively associated with greater severity of SI compared to the nonanhedonic group; no differences in severity of SI were found between the chronically anhedonic and nonanhedonic group at either time point. Anhedonia grouping was not associated with SA history. Conclusion Changes in capacity to experience pleasure may be more informative of near‐term SI than typically low pleasure levels. Future investigation should focus on the relationship between acute anhedonia and imminent suicidal behavior. - Depression and Anxiety, EarlyView.
  

  August 14, 2018   doi: 10.1002/da.22814   open full text
• Predeployment predictors of psychiatric disorder‐symptoms and interpersonal violence during combat deployment.
  Anthony J. Rosellini, Murray B. Stein, David M. Benedek, Paul D. Bliese, Wai Tat Chiu, Irving Hwang, John Monahan, Matthew K. Nock, Nancy A. Sampson, Amy E. Street, Alan M. Zaslavsky, Robert J. Ursano, Ronald C. Kessler.
  Depression and Anxiety. August 13, 2018
  --- - |2+ Background Preventing suicides, mental disorders, and noncombat‐related interpersonal violence during deployment are priorities of the US Army. We used predeployment survey and administrative data to develop actuarial models to identify soldiers at high risk of these outcomes during combat deployment. Methods The models were developed in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) Pre‐Post Deployment Study, a panel study of soldiers deployed to Afghanistan in 2012–2013. Soldiers completed self‐administered questionnaires before deployment and one (T1), three (T2), and nine months (T3) after deployment, and consented to administrative data linkage. Seven during‐deployment outcomes were operationalized using the postdeployment surveys. Two overlapping samples were used because some outcomes were assessed at T1 (n = 7,048) and others at T2–T3 (n = 7,081). Ensemble machine learning was used to develop a model for each outcome from 273 predeployment predictors, which were compared to simple logistic regression models. Results The relative improvement in area under the receiver operating characteristic curve (AUC) obtained by machine learning compared to the logistic models ranged from 1.11 (major depression) to 1.83 (suicidality).The best‐performing machine learning models were for major depression (AUC = 0.88), suicidality (0.86), and generalized anxiety disorder (0.85). Roughly 40% of these outcomes occurred among the 5% of soldiers with highest predicted risk. Conclusions Actuarial models could be used to identify high risk soldiers either for exclusion from deployment or preventive interventions. However, the ultimate value of this approach depends on the associated costs, competing risks (e.g. stigma), and the effectiveness to‐be‐determined interventions. - Depression and Anxiety, EarlyView.
  

  August 13, 2018   doi: 10.1002/da.22807   open full text
• Agreement between self and psychiatrist reporting of suicidal ideation at a Veterans Administration psychiatric emergency clinic.
  Janet R. McClure, Ilanit Tal, Caroline A. Macera, Ming Ji, Caroline M. Nievergelt, Soo Yong Lee, Josh Kayman, Sidney Zisook.
  Depression and Anxiety. August 13, 2018
  --- - |2+ Background With suicide rising in the United States, identifying and preventing suicides is increasingly important. To provide a valuable step toward achieving effective suicide risk assessment, this study examines the agreement between self‐report measures and psychiatrist documentation of suicidal ideation and behaviors (SI) at a Veterans Administration (VA) psychiatric emergency clinic. Methods A total of 377 veterans presenting at a VA psychiatric emergency clinic completed a self‐report survey on SI and other acute risk factors for suicidal behavior. We examined agreement between veterans’ self‐reported SI and psychiatrists’ clinical notes regarding SI. Results A total of 199 veterans (53%) self‐reported SI; 80 psychiatrist notes (21%) indicated SI. Psychiatrists and veterans differed in 44% (164/377) of cases. Among the discordant cases, the veterans’ self‐report was more severe than the psychiatrists’ in 97% of cases. Of the 120 veterans with SI and documented as having no SI by psychiatrists, 31 (26%) reported having a suicide plan and 18 (15%) plan preparations. Findings were similar when controlling for presenting problem, current depression, presence of a standardized suicide risk assessment, psychiatrist training level, past suicide attempt, homelessness, diagnosis of personality, or substance use disorder. Conclusions Agreement between veterans' self‐reports and psychiatrists’ documentation of SI was generally low, with veterans self‐reporting SI significantly more often than psychiatrists documented SI in their clinical notes. This suggests that inclusion of a self‐report questionnaire provides an additional source of data to complement information gleaned from the clinical interview for a more comprehensive risk assessment, but only if actually examined by the clinician. - Depression and Anxiety, EarlyView.
  

  August 13, 2018   doi: 10.1002/da.22813   open full text
• Depression among military spouses: Demographic, military, and service member psychological health risk factors.
  Carrie J. Donoho, Cynthia LeardMann, Christopher A. O'Malley, Kristen H. Walter, Lyndon A. Riviere, John F. Curry, Amy B. Adler.
  Depression and Anxiety. August 13, 2018
  --- - |2+ Background More than a decade of war has strained service members and their families and the psychological health of military spouses is a concern. This study uses data from the largest study of military families in the United States to examine the demographic, military‐specific, and service member mental health correlates of probable diagnosis of major depressive disorder (MDD) among military spouses. Methods Data were from service member‐spouse dyads from all branches of the U.S. military. Demographic and military‐specific factors were assessed using administrative personnel records and survey data. Results Of the 9,038 spouses, 4.9% had a probable diagnosis of MDD. In unadjusted models, spouses of service members who deployed and experiencecd combat‐related events, were enlisted, had a probable posttraumatic stress disorder (PTSD) diagnosis, or screened positive for alcohol misuse were more likely to screen positive for MDD. In adjusted models, only spouses married to enlisted service members or those with PTSD had increased risk for MDD. Other demographic and military‐related factors associated with MDD in spouses included less educational attainment, unemployment, having four or more children, and having prior military service (although not currently serving in the military) in the adjusted models. Conclusions Findings characterize demographic, military, and service member psychological health factors that are associated with depression among military spouses. These findings imply that deployment alone may not negatively affect military spouses, but rather it may be the mental health impact on the service member, especially PTSD that increases the odds for MDD among military spouses. - Depression and Anxiety, EarlyView.
  

  August 13, 2018   doi: 10.1002/da.22820   open full text
• Women's decision making about antidepressant use during pregnancy: A narrative review.
  Catriona Hippman, Lynda G. Balneaves.
  Depression and Anxiety. August 12, 2018
  --- - |2+ Background Depression is common, particularly among women of childbearing age, and can have far‐reaching negative consequences if untreated. Efficacious treatments are available, but little is known about how women make depression treatment decisions during pregnancy. The purpose of this narrative review is to interpretively synthesize literature on women's decision making (DM) regarding antidepressant use during pregnancy. Methods The databases PubMed, CINAHL, and PsycINFO were searched between May 2015 and August 2017 for peer‐reviewed, English‐language papers using terms such as “depression,” “pregnancy,” and “DM.” The literature matrix abstraction method was used to systematically abstract data from full articles that met criteria for inclusion. Results Of the articles abstracted (N = 10), half did not cite a DM theory on which the work was based. Key aspects of DM for this population were need for information and decision support, desire for active participation in DM, reflection on beliefs and values, evaluation of treatment option sequelae, and societal expectations. Treatment DM for depression during pregnancy is particularly impacted by the stigma associated with depression and societal expectations of pregnant women related to medication use during pregnancy. These findings, however, were based on studies of predominantly Caucasian and well‐educated women. Conclusions Women require a nonjudgmental environment, in which shared DM feels safe, to foster positive DM experiences and outcomes. Future research is needed to define how to best support women to make depression treatment decisions in pregnancy, with particular attention to DM in the second and third trimesters of pregnancy. - Depression and Anxiety, EarlyView.
  

  August 12, 2018   doi: 10.1002/da.22821   open full text
• Subthreshold PTSD and PTSD in a prospective‐longitudinal cohort of military personnel: Potential targets for preventive interventions.
  David S. Fink, Jaimie L. Gradus, Katherine M. Keyes, Joseph R. Calabrese, Israel Liberzon, Marijo B. Tamburrino, Gregory H. Cohen, Laura Sampson, Sandro Galea.
  Depression and Anxiety. August 12, 2018
  --- - |2+ Background Prevention of PTSD requires identification of subpopulations contributing most to the population burden of PTSD. This study examines the relative contribution of subthreshold PTSD and probable PTSD on future PTSD in a representative military cohort. Methods We analyze data on 3,457 U.S. National Guard members from the state of Ohio, assessed by telephone annually from 2008 to 2014. At each wave, participants were classified into one of three groups based on the PTSD Checklist: probable PTSD (DSM‐IV‐TR criteria), subthreshold PTSD (Criterion A1, at least one symptom in each cluster, symptom lasting longer than 30 days, and functional impairment), and no PTSD. We calculated the exposure rate, risk ratio (RR), and population attributable fraction (PAF) to determine the burden of future probable PTSD attributable to subthreshold PTSD compared to probable PTSD. Results The annualized prevalence of subthreshold PTSD and probable PTSD was respectively 11.9 and 5.0%. The RR for probable PTSD was twice as great among respondents with probable PTSD the prior interview than that of those with subthreshold PTSD (7.0 vs. 3.4); however, the PAF was considerably greater in participants with subthreshold PTSD the prior interview (PAF = 35%; 95% confidence interval (CI) = 26.0–42.9%) than in those with probable PTSD (PAF = 28.0%; 95% CI = 21.8–33.8%). Results were robust to changes in subthreshold PTSD definition. Conclusions Subthreshold PTSD accounted for a substantial proportion of this population's future PTSD burden. Population‐based preventive interventions, compared to an approach focused exclusively on cases of diagnosable PTSD, is likely to affect the greatest reduction in this population's future PTSD burden. - Depression and Anxiety, EarlyView.
  

  August 12, 2018   doi: 10.1002/da.22819   open full text
• Screening and follow‐up for depression among Arab Americans.
  Florence J. Dallo, Deepak Prabhakar, Julie Ruterbusch, Kendra Schwartz, Edward L. Peterson, Bin Liu, Brian K. Ahmedani.
  Depression and Anxiety. August 12, 2018
  --- - |2+ Background The authors compared proportions and associations of depression screening, major depression, and follow‐up care of Arab Americans compared to non‐Hispanic whites, non‐Hispanic blacks, Asians, and Hispanics. Methods Administrative data was electronically abstracted from a large health system in metropolitan Detroit among 97,918 adult patients in 2014 and 2015. A valid and reliable surname list was used to identify Arab Americans. Using chi‐squares, we examined the relationship between race/ethnicity and depression screening, major depression, and follow‐up care. We calculated odds ratios (OR) and 95% confidence intervals (CI) to examine the relationship between the main independent variable of race/ethnicity and the dependent variables of depression screening and major depression while controlling for confounders. Results Arab American women were 23% less likely to be screened for depression compared to non‐Hispanic white women (OR = 0.77; 95% CI = 0.70, 0.86). The age‐ and sex‐adjusted proportions of major depression were 5.5% for Arab Americans compared to 7.0% for Hispanics, 6.0% for non‐Hispanic blacks, 5.9% for non‐Hispanic whites, and 1.5% for Asians. Arab Americans with major depression were less likely to follow up with a behavioral specialist and more likely to follow up with a primary care physician compared to other racial and ethnic groups. Conclusions Our study adds to the discourse on depression care among Arab Americans by highlighting the existing disparities related to adequate screening and appropriate management of depression. Future studies should include information about the influences of acculturation, culture, stigma, family, and religion on depression care. - Depression and Anxiety, EarlyView.
  

  August 12, 2018   doi: 10.1002/da.22817   open full text
• Glucocorticoid administration restores salience network activity in patients with spider phobia.
  Leila Maria Soravia, Simon Schwab, Nico Weber, Masahito Nakataki, Roland Wiest, Werner Strik, Markus Heinrichs, Dominique Quervain, Andrea Federspiel.
  Depression and Anxiety. August 12, 2018
  --- - |2+ Background Glucocorticoids reduce phobic fear in patients with anxiety disorders. Although the neurobiology of anxiety disorders is not fully understood, convergent structural and functional neuroimaging studies have identified abnormalities in various brain regions, including those in the salience network (SN) and default mode network (DMN). Here, we examine the effects of glucocorticoid administration on SN and DMN activity during the processing of phobic stimuli. Methods We use functional magnetic resonance imaging to record brain activity in 24 female patients with spider phobia who were administered either 20 mg of cortisol or placebo while viewing pictures of spiders. Fourteen healthy female participants were tested with the same task but without substance administration. Independent component analysis (ICA) performed during stimulus encoding identified the SN and DMN as exhibiting synchronized activation in diverse brain regions; thus, we examined the effects of cortisol on these networks. Furthermore, participants had to rate their level of fear at various time points. Results Glucocorticoids reduced phobic fear in patients with spider phobia. The ICA performed during stimulus encoding revealed that activity in the SN and DMN was reduced in placebo‐treated patients versus healthy controls. Brain activity in the SN, but not the DMN, was altered in cortisol‐ versus placebo‐treated patients to a level that was similar to that observed in healthy controls. Conclusions Activity in both the SN and DMN was reduced in patients with spider phobia. Cortisol administration altered the SN activity to a level that was comparable to that found in healthy controls. This alteration in SN activity might reflect the fear‐reducing effects of glucocorticoids in phobia. - Depression and Anxiety, Volume 35, Issue 10, Page 925-934, October 2018.
  

  August 12, 2018   doi: 10.1002/da.22806   open full text
• The relationship between moral injury appraisals, trauma exposure, and mental health in refugees.
  Joel Hoffman, Belinda Liddell, Richard A. Bryant, Angela Nickerson.
  Depression and Anxiety. August 10, 2018
  --- - |2+ Abstract Background Refugees are often exposed to multiple traumatic experiences, leading to elevated rates of psychological disorders. There is emerging evidence that appraisals of traumatic events as violating deeply held moral beliefs and frameworks (i.e., moral injury) impact negatively on refugee mental health. Despite this, no research has systematically investigated moral injury appraisals in refugees. Method Participants were 222 refugees from diverse backgrounds who had recently resettled in Australia. They completed measures of mental health in Arabic, Farsi, Tamil, or English through an online survey. This study first investigated the factor structure of the Moral Injury Appraisals Scale (MIAS), and then examined the relationship between the moral injury factors and key predictor (age, gender, trauma exposure) and outcome (Posttraumatic stress disorder [PTSD] symptom clusters, anger, and depression) variables. Results Confirmatory factor analyses of the MIAS supported a two‐factor model, comprising a Moral Injury‐Other (MI‐Other) factor (i.e., interpreting the violation as being enacted by others) and a Moral Injury‐Self (MI‐Self) factor (i.e., interpreting the violation as being enacted by oneself). Structural equation modeling analyses indicated that both factors were predicted by higher trauma exposure, and both predicted more severe anger and depression. Notably, while MI‐Other was associated with more severe PTSD, MI‐Self was associated with lower levels of intrusions. Conclusion These results suggest that there may be subtypes of moral injury appraisals that are associated with different mental health outcomes. These findings have potential implications for designing treatments that address the psychological impact of the refugee experience. - Depression and Anxiety, EarlyView.
  

  August 10, 2018   doi: 10.1002/da.22787   open full text
• Mindfulness‐based cognitive therapy for patients with chronic, treatment‐resistant depression: A pragmatic randomized controlled trial.
  Mira B. Cladder‐Micus, Anne E.M. Speckens, Janna N. Vrijsen, A. Rogier T. Donders, Eni S. Becker, Jan Spijker.
  Depression and Anxiety. August 08, 2018
  --- - |2+ Background Chronic and treatment‐resistant depressions pose serious problems in mental health care. Mindfulness‐based cognitive therapy (MBCT) is an effective treatment for remitted and currently depressed patients. It is, however, unknown whether MBCT is effective for chronic, treatment‐resistant depressed patients. Method A pragmatic, multicenter, randomized‐controlled trial was conducted comparing treatment‐as‐usual (TAU) with MBCT + TAU in 106 chronically depressed outpatients who previously received pharmacotherapy (≥4 weeks) and psychological treatment (≥10 sessions). Results Based on the intention‐to‐treat (ITT) analysis, participants in the MBCT + TAU condition did not have significantly fewer depressive symptoms than those in the TAU condition (–3.23 [–6.99 to 0.54], d = 0.35, P = 0.09) at posttreatment. However, compared to TAU, the MBCT + TAU group reported significantly higher remission rates (χ2(2) = 4.25, φ = 0.22, P = 0.04), lower levels of rumination (–3.85 [–7.55 to –0.15], d = 0.39, P = 0.04), a higher quality of life (4.42 [0.03–8.81], d = 0.42, P = 0.048), more mindfulness skills (11.25 [6.09–16.40], d = 0.73, P < 0.001), and more self‐compassion (2.91 [1.17–4.65], d = 0.64, P = 0.001). The percentage of non‐completers in the MBCT + TAU condition was relatively high (n = 12, 24.5%). Per‐protocol analyses revealed that those who completed MBCT + TAU had significantly fewer depressive symptoms at posttreatment compared to participants receiving TAU (–4.24 [–8.38 to –0.11], d = 0.45, P = 0.04). Conclusion Although the ITT analysis did not reveal a significant reduction in depressive symptoms of MBCT + TAU over TAU, MBCT + TAU seems to have beneficial effects for chronic, treatment‐resistant depressed patients in terms of remission rates, rumination, quality of life, mindfulness skills, and self‐compassion. Additionally, patients who completed MBCT showed significant reductions in depressive symptoms. Reasons for non‐completion should be further investigated. - Depression and Anxiety, Volume 35, Issue 10, Page 914-924, October 2018.
  

  August 08, 2018   doi: 10.1002/da.22788   open full text
• Alcohol use disorders and insomnia mediate the association between PTSD symptoms and suicidal ideation in Korean firefighters.
  Johanna Inhyang Kim, Heyeon Park, Jeong‐Hyun Kim.
  Depression and Anxiety. July 20, 2018
  --- - |2+ Background There has been a strong association between posttraumatic stress disorder (PTSD) and suicidal ideation, which are both major mental health concerns in firefighters. Alcohol use disorders (AUDs) and insomnia are linked with both PTSD and suicidal ideation, but no studies have examined whether the relationship between PTSD and suicidal ideation can be explained by AUDs and insomnia. The purpose of this study was to investigate the mediating role of AUDs and insomnia in the relationship between PTSD symptoms and suicidal ideation. Methods A total of 7190 Korean firefighters filled out self‐reported questionnaires to assess the number of exposure to incident stressors and the severity of PTSD symptoms, suicidal ideation, AUDs, and insomnia. Hierarchical multivariable linear regression analyses were performed to identify the relationship of AUDs and insomnia with suicidal ideation. Path analyses were applied to investigate the mediation effects of AUDs and insomnia on the relationship between PTSD symptoms and suicidal ideation. Results AUDs and insomnia showed significant associations with suicidal ideation, even after adjusting for demographic factors, number of traumatic events, and PTSD symptoms. The relationship between PTSD symptoms and suicidal ideation was partially mediated by AUDs and insomnia. AUDs also had both direct and indirect effects on suicidal ideation, with the indirect effect mediated by insomnia. Conclusions We presented a model in which AUDs and insomnia mediate the relationship between PTSD symptoms and suicidal ideation in firefighters. Efforts to treat AUDs and alleviate insomnia could be beneficial in minimizing suicidal ideation in firefighters. - Depression and Anxiety, EarlyView.
  

  July 20, 2018   doi: 10.1002/da.22803   open full text
• CBT and positive psychology interventions for clinical depression promote healthy attentional biases: An eye‐tracking study.
  Carmelo Vazquez, Almudena Duque, Ivan Blanco, Teodoro Pascual, Natalia Poyato, Irene Lopez‐Gomez, Covadonga Chaves.
  Depression and Anxiety. July 20, 2018
  --- - |2+ Background Although there is a growing interest in the role of attentional biases in depression, there are no studies assessing changes in these biases after psychotherapeutic interventions. Methods We used a validated eye‐tracking procedure to assess pre–post therapy changes in attentional biases toward emotional information (i.e., happy, sad, and angry faces) when presented with neutral information (i.e., neutral faces). The sample consisted of 75 participants with major depression or dysthymia. Participants were blindly assigned to one of two 10 weekly sessions of group therapy: a cognitive behavior therapy intervention (N = 41) and a positive psychology intervention (N = 34). Results Both treatments were equally efficacious in improving depressive symptoms (p = .0001, η² = .68). A significant change in attentional performance after therapy was observed irrespective of the intervention modality. Comparison of pre–post attentional measures revealed a significant reduction in the total time of fixations (TTF) looking at negative information (i.e., sad and angry faces) and a significant increase in the TTF looking at positive information (i.e., happy faces)—all p < .02. Conclusions Findings reveal for the first time that psychotherapeutic interventions are associated with a significant change in attentional biases as assessed by a direct measure of attention. Furthermore, these changes seem to operate in the same direction typically found in healthy populations (i.e., a bias away from negative information and a parallel bias toward positive information). These findings illustrate the importance of considering attentional biases as clinical markers of depression and suggest the viability of modifying these biases as a potential tool for clinical change. - Depression and Anxiety, Volume 35, Issue 10, Page 966-973, October 2018.
  

  July 20, 2018   doi: 10.1002/da.22786   open full text
• The feasibility and acceptability of a novel anxiety in bipolar disorder intervention compared to treatment as usual: A randomized controlled trial.
  Steven H. Jones, Dawn Knowles, Elizabeth Tyler, Fiona Holland, Sarah Peters, Fiona Lobban, Brian Langshaw, Claire Hilton, Rita Long, Kay Gantt, Rebecca Owen, Chris Roberts, Lisa Riste.
  Depression and Anxiety. July 19, 2018
  --- - |2+ Background Comorbid anxiety is common in bipolar disorder (BD) and associated with worse clinical outcomes including increased suicidality. Despite effective psychological treatments for anxiety, research into treating anxiety in BD is underdeveloped. This paper describes a novel psychological intervention to address anxiety in context of bipolar disorder (AIBD). Methods Adults with BD and clinically significant anxiety symptoms were randomized to AIBD plus treatment as usual (TAU) or TAU alone. AIBD offered 10 sessions of psychological therapy using a formulation‐based approach. Feasibility and acceptability were evaluated through recruitment, retention, therapy attendance, alliance, fidelity, and qualitative feedback. Clinical outcomes were assessed at baseline, 16, 48, and 80 weeks: interim assessments of relapse at 32 and 64 weeks. Results Seventy‐two participants were recruited with 88% retention to 16 weeks and 74% to 80 weeks (similar between arms). Therapy participants attended 7.7 (SD 2.8) sessions. Therapeutic alliance and therapy fidelity were acceptable. Qualitative interviews indicated that participants valued integrated support for anxiety with BD and coping strategies. Some suggested a longer intervention period. Clinical outcomes were not significantly different between arms up to 80 weeks follow‐up. Conclusions AIBD is feasible and acceptable but lack of impact on clinical outcomes indicates that adaptations are required. These are discussed in relation to qualitative feedback and recent literature published since the trial completed. - Depression and Anxiety, Volume 35, Issue 10, Page 953-965, October 2018.
  

  July 19, 2018   doi: 10.1002/da.22781   open full text
• Deficits in emotion recognition are associated with depressive symptoms in youth with disruptive mood dysregulation disorder.
  Pablo Vidal‐Ribas, Melissa A. Brotman, Giovanni A. Salum, Ariela Kaiser, Liana Meffert, Daniel S. Pine, Ellen Leibenluft, Argyris Stringaris.
  Depression and Anxiety. July 13, 2018
  --- - |2+ Abstract Background Although severe irritability is a predictor of future depression according to recent meta‐analytic evidence, other mechanisms for this developmental transition remain unclear. In this study, we test whether deficits in emotion recognition may partially explain this specific association in youth with severe irritability, defined as disruptive mood dysregulation disorder (DMDD). Methods Participants aged 8–20 years (M = 13.3, SD = 2.8) included youth with DMDD, split by low depressive (DMDD/LD; n = 52) and high depressive (DMDD/HD; n = 25) symptoms, and healthy controls (HC; n = 39). A standardized computer task assessed emotion recognition of faces and voices of adults and children expressing happiness, fear, sadness, and anger. A Group (3) × Emotion (4) × Actor (2) × Modality (2) repeated measures analysis of covariance examined the number of errors and misidentification of emotions. Linear regression was then used to assess whether deficits in emotion recognition were predictive of depressive symptoms at a 1 year follow‐up. Results DMDD/HD youth were more likely to interpret happy stimuli as angry and fearful compared to DMDD/LD (happy as angry: p = 0.018; happy as fearful: p = 0.008) and HC (happy as angry: p = 0.014; happy as fearful: p = 0.024). In youth with DMDD, the misidentification of happy stimuli as fearful was associated with higher depressive symptoms at follow‐up (β = 0.43, p = 0.017), independent of baseline depressive and irritability symptoms. Conclusions Deficits in emotion recognition are associated, cross‐sectionally and longitudinally, with depressive symptoms in youth with severe irritability. Future studies should examine the neural correlates that contribute to these associations. - Depression and Anxiety, EarlyView.
  

  July 13, 2018   doi: 10.1002/da.22810   open full text
• Efficacy of probiotics on anxiety—A meta‐analysis of randomized controlled trials.
  Bangshan Liu, Yunan He, Mi Wang, Jin Liu, Yumeng Ju, Yan Zhang, Tiebang Liu, Lingjiang Li, Qi Li.
  Depression and Anxiety. July 11, 2018
  --- - |2+ Background The concept “psychobiotics” claims potential beneficial effect of probiotics on anxiety, whereas findings from clinical trials are inconsistent. Thus, a meta‐analysis is needed to clarify the effect of probiotics on anxiety. Methods Randomized controlled trials (RCTs) assessing the effect of probiotics on anxiety were systematically retrieved from online databases and manually screened for references of relevant published literature through September 1, 2017. Standardized mean difference in change from baseline of anxiety rating scales between probiotics groups and placebo groups was selected as the main effect index. Subgroup analyses were conducted with respect to overall health status of the sample, existence of gastrointestinal symptoms, strains of flora, trial duration, and risk of bias assessment. Publication bias was evaluated by funnel plot and Egger's test. The reliability of the result was assessed by leave‐one‐out sensitivity analysis. Results Twelve studies with 1,551 subjects (871 in probiotics group and 680 in control group) were included. All the studies were rated as low or moderate risk of bias. The meta‐analysis and subgroup analyses all showed no significant difference between probiotics and placebo in alleviating anxiety symptoms. The Egger's test revealed no evidence of significant publication bias. Sensitivity analysis showed that leaving out one study would result in marginal significance. Conclusions The evidence for the efficacy of probiotics in alleviating anxiety, as presented in currently published RCTs, is insufficient. More reliable evidence from clinical trials is needed before a case can be made for promoting the use of probiotics for alleviating anxiety. - Depression and Anxiety, Volume 35, Issue 10, Page 935-945, October 2018.
  

  July 11, 2018   doi: 10.1002/da.22811   open full text
• Posttraumatic stress, uncontrollability, and emotional distress tolerance.
  Lisa Hancock, Richard A. Bryant.
  Depression and Anxiety. July 10, 2018
  --- - |2+ Background Although individuals with posttraumatic stress disorder (PTSD) report poor tolerance for distress, the mechanisms underpinning this are unknown. Cognitive models of PTSD propose that appraisals of lacking or losing control impair adaptation to trauma. This study investigated whether avoidance of emotional distress was affected by loss of control in a web‐based community sample with and without PTSD symptomatology, expecting that those with PTSD may show more detrimental effects following greater loss of control. Methods PTSD‐symptomatic (N = 104) and nonsymptomatic (N = 102) participants initially had baseline controllability appraisals indexed during a task designed to induce an illusion of control over an unwanted stimulus. Participants were then randomized to be able to delay the onset and also control the termination of interference trials during an effortful visual search task, and separately randomized to receive pretask instructions implying either doubtful or certain controllability. Following the manipulation, participants completed a task indexing delay between selecting and playing a purportedly distressing video at their maximum tolerable distress level. Results Controlling for age, sex, and instructional condition, those who experienced greater violation of their initial perceptions of control tended to be more avoidant of emotional distress. There was a significant interaction whereby loss of control was more detrimental for those with PTSD symptoms. Conclusions These initial data suggest that posttraumatic stress exacerbates sensitivity to loss of control, and this appears to directly impact capacity to approach distressing stimuli. - Depression and Anxiety, EarlyView.
  

  July 10, 2018   doi: 10.1002/da.22783   open full text
• Pharmacogenetic testing among patients with mood and anxiety disorders is associated with decreased utilization and cost: A propensity‐score matched study.
  Roy H. Perlis, Rajesh Mehta, Alison M. Edwards, Arun Tiwari, Guido W. Imbens.
  Depression and Anxiety. May 07, 2018
  --- - |2+ Background Naturalistic and small randomized trials have suggested that pharmacogenetic testing may improve treatment outcomes in depression, but its cost‐effectiveness is not known. There is growing enthusiasm for personalized medicine, relying on genetic variation as a contributor to heterogeneity of treatment effects. We sought to examine the relationship between a commercial pharmacogenetic test for psychotropic medications and 6‐month cost of care and utilization in a large commercial health plan. Methods We performed a propensity‐score matched case‐control analysis of longitudinal health claims data from a large US insurer. Individuals with a mood or anxiety disorder diagnosis (N = 817) who received genetic testing for pharmacokinetic and pharmacodynamic variation were matched to 2,745 individuals who did not receive such testing. Outcomes included number of outpatient visits, inpatient hospitalizations, emergency room visits, and prescriptions, as well as associated costs over 6 months. Results On average, individuals who underwent testing experienced 40% fewer all‐cause emergency room visits (mean difference 0.13 visits; P < 0.0001) and 58% fewer inpatient all‐cause hospitalizations (mean difference 0.10 visits; P < 0.0001) than individuals in the control group. The two groups did not differ significantly in number of psychotropic medications prescribed or mood‐disorder related hospitalizations. Overall 6‐month costs were estimated to be $1,948 (SE 611) lower in the tested group. Conclusions Pharmacogenetic testing represents a promising strategy to reduce costs and utilization among patients with mood and anxiety disorders. - Depression and Anxiety, Volume 35, Issue 10, Page 946-952, October 2018.
  

  May 07, 2018   doi: 10.1002/da.22742   open full text
• A decline in depression treatment following FDA antidepressant warnings largely explains racial/ethnic disparities in prescription fills.
  Nicholas J. Carson, Ana M. Progovac, Ye Wang, Benjamin L. Cook.
  Depression and Anxiety. September 29, 2017
  Background The Food and Drug Administration's 2004 antidepressant warning was followed by decreases in antidepressant prescribing for youth. This was due to declines in all types of depression treatment, not just the intended changes in antidepressant prescribing patterns. Little is known about how these patterns varied by race/ethnicity. Method Data are Medicaid claims from four U.S. states (2002–2009) for youth ages 5–17. Interrupted time series analyses measured changes due to the warning in levels and trends, by race/ethnicity, of three outcomes: antidepressant prescription fills, depression treatment visits, and incident fluoxetine prescription fills. Results Prewarning, antidepressant fills were increasing across all racial/ethnic groups, fastest for White youth. Postwarning, there was an immediate drop and continued decline in the rate of fills among White youth, more than double the decline in the rate among Black and Latino youth. Prewarning, depression treatment visits were increasing for White and Latino youth. Postwarning, depression treatment stabilized among Latinos, but declined among White youth. Prewarning, incident fluoxetine fills were increasing for all groups. Postwarning, immediate increases and increasing trends of fluoxetine fills were identified for all groups. Conclusions Antidepressant prescription fills declined most postwarning for White youth, suggesting that risk information may have diffused less rapidly to prescribers or caregivers of minorities. Decreases in depression treatment visits help to explain the declines in antidepressant prescribing and were largest for White youth. An increase in incident fluoxetine fills, the only medication indicated for pediatric depression at the time, suggests that the warning may have shifted prescribing practices.

  September 29, 2017   doi: 10.1002/da.22681   open full text
• Parenting mediates the impact of maternal depression on child internalizing symptoms.
  Jennie M. Kuckertz, Colter Mitchell, Jillian Lee Wiggins.
  Depression and Anxiety. September 29, 2017
  Background To examine the potential mediating role of parenting behaviors in the longitudinal, bidirectional relationships between maternal depression and child internalizing symptoms (i.e. depression and anxiety). Methods We analyzed data from 4,581 mother–child dyads from the Fragile Families and Child Wellbeing Study, assessed when the child was 3, 5, and 9 years old. Data included maternal depression diagnosis, child internalizing symptoms, and parenting behaviors (i.e. psychological aggression, nonviolent discipline, and physical assault). Data were analyzed using cross‐lagged panel models. Results Results indicated bidirectional relationships between maternal depression and child internalizing symptoms over childhood. Mediation analyses suggested that maternal depression led to subsequent increased psychological aggression toward their child, which in turn led to increased child internalizing symptoms. Nonviolent discipline and physical assault did not mediate this relationship. However, greater use of nonviolent discipline at age 5 among all parents predicted higher child internalizing symptoms at age 9. No parenting behaviors were both predicted by earlier child internalizing symptoms and predictive of subsequent maternal depression. Conclusions Our results suggest a bidirectional relationship between child and maternal internalizing psychopathology that is partially explained by depressed mothers’ greater use of psychological aggression toward their children. It is important to note that the size of these effects were small, suggesting that the relationship between parent and child psychopathology is likely additionally explained by factors not assessed in the current study. Nonetheless, these results have implications for prevention and intervention strategies targeting child anxiety and depression.

  September 29, 2017   doi: 10.1002/da.22688   open full text
• Proximal relationships between social support and PTSD symptom severity: A daily diary study of sexual assault survivors.
  Emily R. Dworkin, Sarah E. Ullman, Cynthia Stappenbeck, Charlotte D. Brill, Debra Kaysen.
  Depression and Anxiety. September 28, 2017
  Background In cross‐sectional studies, social support and posttraumatic stress disorder (PTSD) symptoms appear related, in that higher severity of PTSD is associated with lower social support and vice versa. Theoretical models of the causal direction of this relationship differ. Most longitudinal studies suggest that PTSD symptoms erode social support over time, although some suggest that higher social support is prospectively associated with decrease in PTSD symptom severity. It is unclear, though, how social support and PTSD affect each other in the short term. The purpose of this study was to test day‐to‐day relationships between PTSD and social support to elucidate how PTSD and social support influence each other. Methods Using 1173 daily observations from 75 college women who met screening criteria for lifetime sexual assault and past‐month PTSD, this study tested same‐day and next‐day relationships between PTSD and social support using mixed models. Results Within‐person analyses indicated that, when PTSD was higher than usual on a given day, social support was higher the next day. Between‐person analyses suggested that people with generally higher social support tended to have lower PTSD symptoms on a given day, but average PTSD symptom severity was not associated with day‐to‐day fluctuations in social support. Conclusions Rather than eroding in response to daily symptoms, social support might be sought out following increases in PTSD, and when received consistently, might reduce symptoms of PTSD in the short term. Interventions that increase college women's access to social support after sexual assault may thus be helpful in addressing PTSD.

  September 28, 2017   doi: 10.1002/da.22679   open full text
• Error‐related brain activity and internalizing disorder symptom dimensions in depression and anxiety.
  Stephanie M. Gorka, Katie L. Burkhouse, Kaveh Afshar, K. Luan Phan.
  Depression and Anxiety. September 20, 2017
  Background Research suggests that enhanced neural reactivity to errors, measured via the error‐related negativity (ERN), is relatively unique to internalizing psychopathologies (IPs) and symptom clusters characterized by excessive worry and apprehension. However, no prior study has tested the association between the ERN and IP symptom dimensions in a heterogeneous, clinically representative patient population. The current study was designed to address this gap in the literature and clarify the role of the ERN in an adult IP treatment‐seeking patient sample. Method Eighty‐five participants completed a well‐validated flanker task known to robustly elicit the ERN and a battery of questionnaires assessing a range of IP symptoms. All participants had at least one IP diagnosis and over 75% had co‐occurring IPs. A principal components analysis (PCA) was performed on the questionnaire data indicating two distinct factors that characterized the IP sample: affective distress/misery and fear‐based anxiety. Results Analyses indicated that within this sample, an enhanced ERN, but not CRN, was associated with greater fear‐based anxiety symptoms but had no relation with distress/misery symptoms. Conclusions Together, these findings indicate that an enhanced ERN may not be specific to worry/apprehension and may extend to the IP fear dimension. The results also converge with a broader literature suggesting that fear‐based psychopathology is characterized by an exaggerated reactivity to threat and this objective, psychophysiological response tendency may distinguish fear disorders from distress.

  September 20, 2017   doi: 10.1002/da.22648   open full text
• The relationship between depression and chronotype: A longitudinal assessment during childhood and adolescence.
  Dustin A. Haraden, Benjamin C. Mullin, Benjamin L. Hankin.
  Depression and Anxiety. September 08, 2017
  Background/objective During adolescence, chronotype shifts toward “eveningness.” “Eveningness” is related to negative physical and mental health outcomes. Little is known about what influences the shift in chronotype beyond pubertal status. The current study examined the influence of earlier depression predicting later individual differences in adolescent chronotype, accounting for pubertal status, and the prospective prediction of later increases in depression from earlier chronotype. Methods Youth (age M = 12.06, SD = 2.35; 56.5% girls) from the community completed repeated assessments of depression, including both self‐reports (14 assessments) and diagnostic interviews (eight assessments), over a 48‐month period. At the 36‐month timepoint, participants completed chronotype and pubertal development measures. Regression and ANOVA analyses examined: (1) the influence of earlier depression levels (baseline to 36 months) upon chronotype, and (2) chronotype (at 36 months) upon later depression (48 months). Results Youth with higher earlier depression symptoms (β = −0.347, P < .001) and history of depression diagnosis (β = −0.13, P = .045) showed a greater eveningness preference controlling for pubertal status, age, and gender. Further, depression diagnosis history interacted with pubertal status to predict chronotype: (F(1,243) = 4.171, P = .045) such that the influence of depression on chronotype was greatest among postpubertal youth (t = 3.271, P = .002). Chronotype (greater eveningness preference) predicted prospective increases in depression symptoms (β = −0.16, P = .03) and onset of depressive episode (b = −0.085, OR = 0.92, P = .03) 1 year later. Conclusion Depression, experienced earlier in life, predicts greater preference for eveningness, especially among postpubertal youth. In turn, later depression is predicted by evening preference. These findings suggest the reciprocal interplay between mood and biological rhythms, especially depression and chronotype, during adolescence.

  September 08, 2017   doi: 10.1002/da.22682   open full text
• The impact of enhancing perceived self‐efficacy in torture survivors.
  Naser Morina, Richard A. Bryant, Emma L. Doolan, Chantal Martin‐Sölch, Michael Plichta, Monique C. Pfaltz, Ulrich Schnyder, Matthis Schick, Angela Nickerson.
  Depression and Anxiety. September 07, 2017
  Background Perceived self‐efficacy (SE) is an important factor underlying psychological well‐being. Refugees suffer many experiences that can compromise SE. This study tested the impact of enhancing perceived SE on coping with trauma reminders and distress tolerance in tortured refugees. Methods Torture survivors (N = 40) were administered a positive SE induction in which they retrieved mastery‐related autobiographical memories, or a non‐SE (NSE) induction, and then viewed trauma‐related images. Participants rated their distress following presentation of each image. Participants then completed a frustration‐inducing mirror‐tracing task to index distress tolerance. Results Participants in the SE condition reported less distress and negative affect, and improved coping in relation to viewing the trauma‐related images than those in the NSE condition. The SE induction also led to greater persistence with the mirror‐tracing task than the NSE induction. Conclusions These findings provide initial evidence that promoting SE in tortured refugees can assist with managing distress from trauma reminders, and promoting greater distress tolerance. Enhancing perceived SE in tortured refugees may increase their capacity to tolerate distress during therapy, and may be a useful means to improve treatment response.

  September 07, 2017   doi: 10.1002/da.22684   open full text
• Endogenous oxytocin is associated with the experience of compassion and recalled upbringing in Borderline Personality Disorder.
  Andreas Ebert, Marc‐Andreas Edel, Paul Gilbert, Martin Brüne.
  Depression and Anxiety. September 07, 2017
  Background/Objective The role of the neuropeptide oxytocin (OT) in Borderline Personality Disorder (BPD) is poorly understood. It is particularly unknown how early experiences with caregivers moderate the action of OT in BPD. Here, we examined the association of plasma OT levels in BPD patients with the experience of compassion and recalled parental behavior during childhood. Methods Fifty‐seven BPD patients and 43 healthy controls participated in the study. OT plasma levels were analyzed by radioimmunoassay. Subjects additionally completed questionnaires focusing on fears of compassion (FOC) and recalled upbringing (“Questionnaire of Recalled Parental Rearing Behavior/Fragebogen zum erinnerten elterlichen Erziehungsverhalten,” FEE). Results BPD patients had significantly lower OT plasma levels than healthy controls and differed significantly on all FOC and FEE scales; BPD patients had higher FOC scores (indicating more aversion of being compassionate to themselves and others and receiving compassion from others). They also differed in recalled parenting. In the BPD group, scores of the FOC scale “fear of compassion from others” were significantly negatively correlated with OT levels. Moreover, recalled “emotional warmth” of their parents during childhood was positively correlated with OT plasma levels of BPD subjects. No such correlations were found in the control group. Conclusion Our results corroborate findings from previous studies reporting lower OT levels in patients with BPD. Moreover, peripheral OT seems to be linked with the tolerance of compassionate feelings and early experiences with caregivers. This is consistent with other findings that OT is an important mediator of the experience of emotional warmth from others.

  September 07, 2017   doi: 10.1002/da.22683   open full text
• Meta‐analysis: Risk of hyperhidrosis with second‐generation antidepressants.
  Chad Beyer, Kiley Cappetta, Jessica A. Johnson, Michael H. Bloch.
  Depression and Anxiety. September 07, 2017
  Background Our goal was to quantify the risk of hyperhidrosis associated with commonly used antidepressant agents and examine the impact of medication class, pharmacodynamics, and dose on risk of hyperhidrosis. Methods We conducted a PubMed search to identify all double‐blind, randomized, placebo‐controlled trials examining the efficacy of second‐generation antidepressant medications in the treatment of adults with a depressive disorder, anxiety disorders, or obsessive‐compulsive disorder. We used a random‐effects meta‐analysis to examine the pooled risk ratio of hyperhidrosis reported as a side effect in adults treated with second‐generation antidepressants compared to placebo. We used stratified subgroup analysis and metaregression to examine the effects of medication type, class, dosage, indication, and receptor affinity profile on the measured risk of hyperhidrosis. Results We identified 76 trials involving 28,544 subjects. There was no significant difference in the risk of hyperhidrosis between serotonin–norepinephrine reuptake inhibitors (SNRI) [risk ratio (RR) = 3.17, 95% CI: 2.63–3.82] and selective serotonin reuptake inhibitors (SSRI) (RR = 2.93, 95% CI: 2.46–3.47) medications compared to placebo. All antidepressant medications were associated with a significantly increased risk of hyperhidrosis except fluvoxamine (RR = 0.56, 95% CI: 0.12–2.53), bupropion (RR = 1.23, 95% CI: 0.57–2.67), and vortioxetine (RR = 1.35, 95% CI: 0.79–2.33). The dose of SSRI/SNRI medications was not significantly associated with the risk of hyperhidrosis. Increased risk of hyperhidrosis was associated with increased affinity of SSRI/SNRI medications to the dopamine transporter. Conclusion Risk of hyperhidrosis was significantly increased with most antidepressant medications but was associated with dopamine transporter affinity.

  September 07, 2017   doi: 10.1002/da.22680   open full text
• Early childhood trajectories of separation anxiety: Bearing on mental health, academic achievement, and physical health from mid‐childhood to preadolescence.
  Marco Battaglia, Gabrielle Garon‐Carrier, Sylvana M. Côté, Ginette Dionne, Evelyne Touchette, Frank Vitaro, Richard E. Tremblay, Michel Boivin.
  Depression and Anxiety. August 18, 2017
  Background Separation anxiety disorder is the most prevalent childhood anxiety condition, but no study assessed children for separation anxiety at preschool age and followed them longitudinally and directly until mid‐childhood/early adolescence. Methods Multi‐informant (children, teachers, family), multipoint (at age 8, 10, 12, 13) assessments of 1,290 children of the Quebec Longitudinal Study of Child Development, who had been categorized between age 1.5 and 6 into four specific separation anxiety trajectories (1, low‐persistent; 2, low‐increasing; 3, high‐decreasing, and the less common: 4, high‐increasing) by growth mixture modeling. Participants in the high‐increasing trajectory were compared to participants in the other three trajectories for: (a) child's internalizing and externalizing problem behavior; (b) physical health; (c) academic achievement; (d) maternal anxiety. Results Multivariate analyses of variance/covariance at separate time points showed the high‐increasing trajectory mostly associated with: (a) higher internalizing, but not externalizing, behavior; (b) worse academic achievement (most consistently by comparisons to the normative low‐persistent trajectory; (c) higher rates of maternal panic/agoraphobic anxiety; (d) worse physical health (most consistently by comparisons to the low‐persistent trajectory). The high‐increasing trajectory had twofold to threefold higher incidences of physical illnesses than the normative low‐persistent group; this was specific for headaches at age 12 years, chronic asthma at age 10 and 13, and having received asthma‐related medication during the past 12 months. Conclusions High‐increasing separation anxiety in preschool maintains longitudinal relationships to independent health and academic outcomes, at least until preadolescence. This knowledge can inform the deployment of clinical resources at the earlier signs of the more impairing manifestations.

  August 18, 2017   doi: 10.1002/da.22674   open full text
• Nonremission and time to remission among remitters in major depressive disorder: Revisiting STAR*D.
  Ramin Mojtabai.
  Depression and Anxiety. August 18, 2017
  Background Some individuals with major depressive disorder do not experience a remission even after one or more adequate treatment trials. In some others who experience remission, it happens at variable times. This study sought to estimate the prevalence of nonremission in a large sample of patient participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial and to identify correlates of nonremission and time to remission among remitters. Methods Using data from 3,606 participants of STAR*D, the study used cure regression modeling to estimate nonremission and jointly model correlates of nonremission and time to remission among the remitters. Results Overall, 14.7% of the STAR*D participants were estimated to be nonremitters. Among remitters, the rate of remission declined over time. Greater severity, poorer physical health, and poor adherence with treatments were associated with both nonremission and a longer time to remission among the remitters in multivariable analyses, whereas unemployment, not having higher education, and longer duration of current episode were uniquely associated with nonremission; whereas, treatment in specialty mental health settings, poorer mental health functioning, and greater impairment in role functioning with a longer time to remission among remitters. Conclusion Poor treatment adherence and poor physical health appear to be common risk factors for both nonremission and longer time to remission, highlighting the importance of integrated care models that address both medical and mental healthcare needs and interventions aimed at improving treatment adherence.

  August 18, 2017   doi: 10.1002/da.22677   open full text
• COMT val158met polymorphism links to altered fear conditioning and extinction are modulated by PTSD and childhood trauma.
  Jessica Deslauriers, Dean T. Acheson, Adam X. Maihofer, Caroline M. Nievergelt, Dewleen G. Baker, Mark A. Geyer, Victoria B. Risbrough,.
  Depression and Anxiety. August 18, 2017
  Background Risk for posttraumatic stress disorder (PTSD) is thought to be mediated by gene × environment (G × E) interactions that affect core cognitive processes such as fear learning. The catechol‐O‐methyltransferase (COMT) val158met polymorphism has been associated with risk for PTSD and impaired fear inhibition. We used a large, relatively homogenous population to (1) replicate previous findings of poor fear inhibition in COMT Met/Met carriers with PTSD; (2) determine if COMT association with fear inhibition is moderated by childhood trauma (CT), an environmental risk factor for PTSD; and (3) determine if COMT is associated with altered fear processes after recent exposure to combat trauma. Methods Male Marines and Navy Corpsmen of European‐American ancestry were assessed prior to (n = 714) and 4–6 months after deployment to Afghanistan (n = 452). Acquisition and extinction of fear‐potentiated startle, childhood and combat trauma history, and PTSD diagnosis were assessed at both time points. Results Before deployment, Met/Met genotype was associated with fear inhibition deficits in participants with current PTSD; however, this association was dependent on CT exposure. After deployment, combat trauma was associated with a modest reduction in fear extinction in Met/Met compared with Val/Val carriers. There were no associations of COMT genotype with fear extinction within healthy and non‐traumatized individuals. Conclusions These findings support the hypothesis that G × E interactions underlie associations of COMT val158met with fear inhibition deficits. These studies confirm that Met/Met carriers with PTSD have poor fear inhibition, and support further research in understanding how this polymorphism might impact response to extinction‐based therapies.

  August 18, 2017   doi: 10.1002/da.22678   open full text
• Amygdala and regional volumes in treatment‐resistant versus nontreatment‐resistant depression patients.
  Anca‐Larisa Sandu, Eric Artiges, André Galinowski, Thierry Gallarda, Frank Bellivier, Hervé Lemaitre, Bernard Granger, Damien Ringuenet, Eleni T. Tzavara, Jean‐Luc Martinot, Marie‐Laure Paillère Martinot.
  Depression and Anxiety. August 09, 2017
  Background Although treatment‐resistant and nontreatment‐resistant depressed patients show structural brain anomalies relative to healthy controls, the difference in regional volumetry between these two groups remains undocumented. Methods A whole‐brain voxel‐based morphometry (VBM) analysis of regional volumes was performed in 125 participants’ magnetic resonance images obtained on a 1.5 Tesla scanner; 41 had treatment‐resistant depression (TRD), 40 nontreatment‐resistant depression (non‐TRD), and 44 were healthy controls. The groups were comparable for age and gender. Bipolar/unipolar features as well as pharmacological treatment classes were taken into account as covariates. Results TRD patients had higher gray matter (GM) volume in the left and right amygdala than non‐TRD patients. No difference was found between the TRD bipolar and the TRD unipolar patients, or between the non‐TRD bipolar and non‐TRD unipolar patients. An exploratory analysis showed that lithium‐treated patients in both groups had higher GM volume in the superior and middle frontal gyri in both hemispheres. Conclusions Higher GM volume in amygdala detected in TRD patients might be seen in perspective with vulnerability to chronicity, revealed by medication resistance.

  August 09, 2017   doi: 10.1002/da.22675   open full text
• How willing are you? Willingness as a predictor of change during treatment of adults with obsessive–compulsive disorder.
  Adam M. Reid, Lauryn E. Garner, Nathaniel Kirk, Christina Gironda, Jason W. Krompinger, Brian P. Brennan, Brittany M. Mathes, Sadie Cole Monaghan, Eric D. Tifft, Marie‐Christine André, Jordan Cattie, Jesse M. Crosby, Jason A. Elias.
  Depression and Anxiety. July 17, 2017
  Objective Exposure and response prevention (ERP) is an effective treatment for individuals with obsessive–compulsive disorder (OCD), yet a substantial number of individuals with OCD do not fully respond to this intervention. Based on emerging experimental and clinical research on acceptance, this study sought to explore whether willingness to experience unpleasant thoughts, emotions, and bodily sensations during ERP was associated with improved treatment response. Methods Two hundred eighty‐eight adults with OCD receiving residential ERP provided self‐rated willingness and other exposure‐related variables during each daily coached ERP session. Obsessive–compulsive and depressive symptom severity was assessed every week. Multilevel modeling was used to study the impact of willingness on treatment outcome during the first 6 weeks of residential care. Results Data indicated that individuals with higher willingness during ERP reported faster symptom reduction during residential treatment, even when controlling for length of stay, psychopharmacological intervention, depression, adherence, and rituals performed during ERP. These results appear to have both statistical and clinical significance. Conclusions Willingness to fully experience unpleasant and unwanted thoughts, emotions, and bodily sensations during exposures appears to be a marker of successful exposure therapy in adults with OCD. Future research should examine how willingness may enhance extinction learning during ERP.

  July 17, 2017   doi: 10.1002/da.22672   open full text
• Treatment of premenstrual dysphoria with continuous versus intermittent dosing of oral contraceptives: Results of a three‐arm randomized controlled trial.
  Tory A. Eisenlohr‐Moul, Susan S. Girdler, Jacqueline L. Johnson, Peter J. Schmidt, David R. Rubinow.
  Depression and Anxiety. July 17, 2017
  Background Although traditionally dosed combined oral contraceptives (COCs) (21 days of active pills, 7 days of inactive pills) have not been demonstrated as superior to placebo for the treatment of premenstrual dysphoria (PMD), some randomized controlled trials (RCTs) indicate that oral contraceptives administered with a shortened or eliminated hormone‐free interval are superior to placebo. However, results of such trials are mixed, and no existing studies have directly compared continuous and intermittent dosing schedules of the same oral contraceptive. The present study compared placebo, intermittent dosing of oral contraceptives, and continuous dosing of contraceptives for the treatment of PMD. Methods Fifty‐five women with prospectively confirmed PMD completed a three‐arm, RCT in which they were randomized to 3 months of placebo (n = 22), intermittent drospirenone/ethinyl estradiol dosed on a 21–7 schedule (n = 17), or continuous drospirenone/estradiol (n = 16) following a baseline assessment month. Results All three groups demonstrated similar, robust reductions in premenstrual symptoms over time. A marked placebo response was observed. Conclusions The study fails to replicate a uniquely beneficial effect of continuous COC on PMD. Additional work is needed to understand the psychosocial context bolstering the placebo response in women with PMD.

  July 17, 2017   doi: 10.1002/da.22673   open full text
• Prediction of treatment outcomes to exercise in patients with nonremitted major depressive disorder.
  Chad D. Rethorst, Charles C. South, A. John Rush, Tracy L. Greer, Madhukar H. Trivedi.
  Depression and Anxiety. July 03, 2017
  Background Only one‐third of patients with major depressive disorder (MDD) achieve remission with initial treatment. Consequently, current clinical practice relies on a “trial‐and‐error” approach to identify an effective treatment for each patient. The purpose of this report was to determine whether we could identify a set of clinical and biological parameters with potential clinical utility for prescription of exercise for treatment of MDD in a secondary analysis of the Treatment with Exercise Augmentation in Depression (TREAD) trial. Methods Participants with nonremitted MDD were randomized to one of two exercise doses for 12 weeks. Participants were categorized as “remitters” (≤12 on the IDS‐C), nonresponders (<30% drop in IDS‐C), or neither. The least absolute shrinkage and selection operator (LASSO) and random forests were used to evaluate 30 variables as predictors of both remission and nonresponse. Predictors were used to model treatment outcomes using logistic regression. Results Of the 122 participants, 36 were categorized as remitters (29.5%), 56 as nonresponders (45.9%), and 30 as neither (24.6%). Predictors of remission were higher levels of brain‐derived neurotrophic factor (BDNF) and IL‐1B, greater depressive symptom severity, and higher postexercise positive affect. Predictors of treatment nonresponse were low cardiorespiratory fitness, lower levels of IL‐6 and BDNF, and lower postexercise positive affect. Models including these predictors resulted in predictive values greater than 70% (true predicted remitters/all predicted remitters) with specificities greater than 25% (true predicted remitters/all remitters). Conclusions Results indicate feasibility in identifying patients who will either remit or not respond to exercise as a treatment for MDD utilizing a clinical decision model that incorporates multiple patient characteristics.

  July 03, 2017   doi: 10.1002/da.22670   open full text
• Examining the scope and patterns of deliberate self‐injurious cutting content in popular social media.
  Elizabeth M. Miguel, Tommy Chou, Alejandra Golik, Danielle Cornacchio, Amanda L. Sanchez, Mariah DeSerisy, Jonathan S. Comer.
  Depression and Anxiety. June 29, 2017
  Background Social networking services (SNS) have rapidly become a central platform for adolescents’ social interactions and media consumption patterns. The present study examined a representative sample of publicly accessible content related to deliberate self‐injurious cutting across three SNS platforms: Twitter, Tumblr, and Instagram. Methods Data collection simulated searches for publicly available deliberate self‐injury content on Twitter, Tumblr, and Instagram. Over a six‐month period at randomly generated time points, data were obtained by searching “#cutting” on each SNS platform and collecting the first 10 posts generated. Independent evaluators coded posts for presence of the following: (a) graphic content, (b) negative self‐evaluations, (c) references to mental health terms, (d) discouragement of deliberate self‐injury, and (e) recovery‐oriented resources. Differences across platforms were examined. Results Data collection yielded a sample of 1,155 public posts (770 of which were related to mental health). Roughly 60% of sampled posts depicted graphic content, almost half included negative self‐evaluations, only 9.5% discouraged self‐injury, and <1% included formal recovery resources. Instagram posts displayed the greatest proportion of graphic content and negative self‐evaluations, whereas Twitter exhibited the smallest proportion of each. Conclusions Findings characterize the graphic nature of online SNS deliberate self‐injury content and the relative absence of SNS‐posted resources for populations seeking out deliberate self‐injurious cutting content. Mental health professionals must recognize the rapidly changing landscape of adolescent media consumption, influences, and social interaction as they may pertain to self‐harm patterns.

  June 29, 2017   doi: 10.1002/da.22668   open full text
• Transdiagnostic emotional vulnerabilities linking obsessive‐compulsive and depressive symptoms in a community‐based sample of adolescents.
  Gregory S. Chasson, Mariel S. Bello, Alexandria M. Luxon, Trevor A. A. Graham, Adam M. Leventhal.
  Depression and Anxiety. June 29, 2017
  Background : Transdiagnostic emotional vulnerabilities are suspected to underlie psychopathologic comorbidity but have received little attention in adolescent emotional pathology literature. We examined distress tolerance, anxiety sensitivity, and anhedonia as concomitant transdiagnostic mechanisms that account for (i.e., statistically mediate) the covariance between adolescent obsessive‐compulsive disorder (OCD) and major depressive disorder (MDD) symptoms. Method Data on MDD, OCD, and the three aforementioned transdiagnostic vulnerabilities were collected from a community‐based sample of 3,094 ninth graders in a large metropolitan area and analyzed using mixed effects modeling to evaluate mediation effects. Results Individually and when controlling for each other, all three transdiagnostic vulnerabilities mediated the relation between OCD and MDD symptoms both before and after adjusting for demographics. Conclusions Distress tolerance, anxiety sensitivity, and anhedonia may be unique mechanisms accounting for comorbidity between OCD and MDD symptoms in youth. Longitudinal evaluation of these candidate transdiagnostic emotional vulnerabilities in adolescent OCD‐MDD comorbidity is warranted.

  June 29, 2017   doi: 10.1002/da.22669   open full text
• Atypical depression and double depression predict new‐onset cardiovascular disease in U.S. adults.
  Stephanie M. Case, Manisha Sawhney, Jesse C. Stewart.
  Depression and Anxiety. June 22, 2017
  BACKGROUND Although depression is a risk factor for cardiovascular disease (CVD), it is unknown whether this risk varies across depressive disorder subtypes. Thus, we investigated atypical major depressive disorder (MDD) and double depression as predictors of new‐onset CVD in a nationally representative sample of U.S. adults. METHODS Prospective data from 28,726 adults initially free of CVD who participated in Wave 1 (2001–2002) and Wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were examined. Lifetime depressive disorder subtypes (Wave 1) and incident CVD (Wave 2) were determined by structured interviews. RESULTS We identified 1,116 incident CVD cases. In demographics adjusted models, the atypical MDD group had a higher odds of incident CVD than the no depression history (OR = 2.19, 95% CI: 1.71–2.81, P < .001), dysthymic disorder only (OR = 1.61, 95% CI: 1.08–2.39, P = .019), and nonatypical MDD (OR = 1.46, 95% CI: 1.11–1.91, P = .006) groups. Likewise, the double depression group had a higher odds of incident CVD than the no depression history (OR = 2.17, 95% CI: 1.92–2.45, P < .001), dysthymic disorder only (OR = 1.59, 95% CI: 1.16–2.19, P = .004), and MDD only (OR = 1.46, 95% CI: 1.20–1.77, P < .001) groups. Relationships were similar but attenuated after adjustment for CVD risk factors and anxiety disorders. CONCLUSIONS Adults with atypical MDD or double depression may be subgroups of the depressed population at particularly high risk of new‐onset CVD. Thus, these subgroups may (a) be driving the overall depression–CVD relationship and (b) be in need of earlier and/or more intense CVD primary prevention efforts to reduce their excess CVD burden.

  June 22, 2017   doi: 10.1002/da.22666   open full text
• Increased neural response to social rejection in major depression.
  Poornima Kumar, Gordon D Waiter, Magda Dubois, Maarten Milders, Ian Reid, J Douglas Steele.
  Depression and Anxiety. June 20, 2017
  Background Being a part of community is critical for survival and individuals with major depressive disorder (MDD) have a greater sensitivity to interpersonal stress that makes them vulnerable to future episodes. Social rejection is a critical risk factor for depression and it is said to increase interpersonal stress and thereby impairing social functioning. It is therefore critical to understand the neural correlates of social rejection in MDD. Methods To this end, we scanned 15 medicated MDD and 17 healthy individuals during a modified cyberball passing game, where participants were exposed to increasing levels of social exclusion. Neural responses to increasing social exclusion were investigated and compared between groups. Results We showed that compared to controls, MDD individuals exhibited greater amygdala, insula, and ventrolateral prefrontal cortex activation to increasing social exclusion and this correlated negatively with hedonic tone and self‐esteem scores across all participants. Conclusions These preliminary results support the hypothesis that depression is associated with hyperactive response to social rejection. These findings highlight the importance of studying social interactions in depression, as they often lead to social withdrawal and isolation.

  June 20, 2017   doi: 10.1002/da.22665   open full text
• Maternal depression and bullying victimization among adolescents: Results from the 2004 Pelotas cohort study.
  Catarina Machado Azeredo, Iná S. Santos, Aluísio J. D. Barros, Fernando C. Barros, Alicia Matijasevich.
  Depression and Anxiety. June 20, 2017
  Background Maternal depression impacts on several detrimental outcomes during a child's life course, and could increase their risk of victimization. This longitudinal study examined the association between antenatal maternal depression, postnatal trajectories, and current maternal depression and offspring bullying victimization at 11 years. Methods We included 3,441 11‐year‐old adolescents from the 2004 Pelotas Cohort Study. Antenatal maternal depression, postnatal trajectories, and current maternal depression data were assessed during the follow‐up waves. Bullying victimization was self‐reported by the adolescents. We used ordinal logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (CIs), for the association between maternal depression and offspring bullying victimization. Results The most prevalent type of bullying was verbal victimization (37.9%). We observed a positive association between antenatal maternal depression, postnatal trajectories, and current maternal depression and physical bullying victimization. Maternal mood symptoms during pregnancy were associated with physical (OR = 1.30, 95%CI = 1.11–1.53), verbal (OR = 1.29, 95%CI = 1.12–1.49), and any victimization (OR = 1.22, 95%CI = 1.05–1.41). Severe current maternal depression was associated with physical (OR = 1.34, 95%CI = 1.10–1.62), social manipulation (OR = 1.29, 95%CI = 1.08–1.53), attacks on property (OR = 1.30, 95%CI = 1.08–1.57) and any victimization (OR = 1.32, 95%CI = 1.12–1.56). Regarding maternal depression trajectories, the “chronic‐high” group was associated with higher risk of social manipulation, attacks on property and any victimization, than the “low” group. Conclusions Our results strengthen the evidence of association between maternal depression and offspring bullying victimization, and physical victimization appears to be the main component. Further studies are warranted to confirm our findings and to elucidate the theoretical pathways for this longitudinal association.

  June 20, 2017   doi: 10.1002/da.22662   open full text
• Genetic variants in 5‐HTTLPR, BDNF, HTR1A, COMT, and FKBP5 and risk for treated depression after cancer diagnosis.
  Nis P. Suppli, Jens D. Bukh, Terrie E. Moffitt, Avshalom Caspi, Christoffer Johansen, Anne Tjønneland, Lars V. Kessing, Susanne O. Dalton.
  Depression and Anxiety. June 07, 2017
  Background The role of gene–environment interactions in the pathogenesis of depression is unclear. Previous studies addressed vulnerability for depression after childhood adversity and stressful life events among carriers of numerous specific genetic variants; however, the importance of individual genetic variants, the environmental exposures with which they interact, and the magnitude of the risk conveyed by these interactions remain elusive. Methods We included 7,320 people with a first primary cancer identified in the prospective Diet, Cancer and Health study in an exposed‐only cohort study. The mean age of the individuals was 68 years (5th, 95th percentiles: 58, 78) at cancer diagnosis. Using Cox regression models and cumulative incidence plots, we analyzed the associations between genetic variants in 5‐HTTLPR, BDNF, HTR1A, COMT, and FKBP5 and use of antidepressants as well as hospital contact for depression after diagnosis of cancer. Results Overall, we observed no statistically significant associations, with nonsignificant hazard ratio estimates for use of antidepressants of 0.95–1.07. Conclusions This study of elderly people indicates that it is unlikely that the investigated genetic variants are clinically relevantly associated with depression after diagnosis of cancer. The mechanisms for gene–environment interactions in younger individuals are probably different, and we advise caution in extrapolating our results to early life stress. However, conclusion from the present study might be generalizable to elderly persons exposed to other stressful life events.

  June 07, 2017   doi: 10.1002/da.22660   open full text
• Internet‐based guided self‐help for posttraumatic stress disorder (PTSD): Randomized controlled trial.
  Catrin E. Lewis, Daniel Farewell, Vicky Groves, Neil J. Kitchiner, Neil P. Roberts, Tracey Vick, Jonathan I. Bisson.
  Depression and Anxiety. May 29, 2017
  Background There are numerous barriers that limit access to evidence‐based treatment for posttraumatic stress disorder (PTSD). Internet‐based guided self‐help is a treatment option that may help widen access to effective intervention, but the approach has not been sufficiently explored for the treatment of PTSD. Methods Forty two adults with DSM‐5 PTSD of mild to moderate severity were randomly allocated to internet‐based self‐help with up to 3 h of therapist assistance, or to a delayed treatment control group. The internet‐based program included eight modules that focused on psychoeducation, grounding, relaxation, behavioural activation, real‐life and imaginal exposure, cognitive therapy, and relapse prevention. The primary outcome measure was reduction in clinician‐rated traumatic stress symptoms using the clinician administered PTSD scale for DSM‐V (CAPS‐5). Secondary outcomes were self‐reported PTSD symptoms, depression, anxiety, alcohol use, perceived social support, and functional impairment. Results Posttreatment, the internet‐based guided self‐help group had significantly lower clinician assessed PTSD symptoms than the delayed treatment control group (between‐group effect size Cohen's d = 1.86). The difference was maintained at 1‐month follow‐up and dissipated once both groups had received treatment. Similar patterns of difference between the two groups were found for depression, anxiety, and functional impairment. The average contact with treating clinicians was 2½ h. Conclusions Internet‐based trauma‐focused guided self‐help for PTSD is a promising treatment option that requires far less therapist time than current first line face‐to‐face psychological therapy.

  May 29, 2017   doi: 10.1002/da.22645   open full text
• Clinical and neurobiological effects of aerobic exercise in dental phobia: A randomized controlled trial.
  Brigitt L. Lindenberger, Jens Plag, Sarah Schumacher, Katharina Gaudlitz, Sophie Bischoff, Thomas Bobbert, Fernando Dimeo, Moritz B. Petzold, Clemens Kirschbaum, Zsuzsa Dudás, Andreas Ströhle.
  Depression and Anxiety. May 26, 2017
  Background Physical activity has shown to be effective in anxiety disorders. For specific phobia, no studies are available that systematically examined the effects of an aerobic exercise intervention on phobic fear within a randomized‐controlled design. Therefore, we investigated the acute effect of a standardized aerobic training on clinical symptoms of dental phobia as well as on stress‐related neurobiological markers. Methods Within a crossover design, 30 patients with dental phobia (mean age: 34.1 years; mean score of the Dental Anxiety Scale: 18.8) underwent two minor dental interventions separated by 7 days. Dental treatment was performed after 30 min of physical activity at either 20% VO2 max (control) or 70% VO2 max (intervention), respectively. To control for habituation, patients were randomly assigned to one of the two conditions prior to the first intervention. Moreover, saliva samples were collected at five times in order to determine changes in salivary cortisol (sC) and alpha‐amylase (sAA) due to treatment. Results In comparison to baseline, aerobic exercise within 70% VO2 max significantly reduced clinical anxiety and sC concentrations before, during, and after the dental treatment. In contrast, the control condition led to decreased sAA levels at different time points of measurement. Habituation occurred at the second study day, independent of the order. Conclusions Our study provides evidence for an effect of moderate–intense exercise on clinical symptoms and sC in patients with dental phobia. Therefore, acute aerobic exercise might be a simple and low‐cost intervention to reduce disorder‐specific phobic fear.

  May 26, 2017   doi: 10.1002/da.22659   open full text
• Uncertainty increases neural indices of attention in obsessive‐compulsive disorder.
  Raoul Dieterich, Tanja Endrass, Norbert Kathmann.
  Depression and Anxiety. May 25, 2017
  Background Patients with obsessive‐compulsive disorder (OCD) experience abnormally high levels of uncertainty, and unpredictability is evaluated negatively and not well tolerated. The current study examined neural correlates of attentional processing in response to experimentally induced uncertainty in OCD. Methods Twenty‐four OCD patients and 24 healthy controls performed a task where neutral and negative pictures were preceded by a cue, either being predictive (certain condition) or nonpredictive (uncertain condition) of subsequent picture valence. We examined prepicture anticipatory attention through α (∼8–12 Hz) suppression, and attentional allocation during picture presentation with the P1, N1, P2, N2, and late positive potential (LPP) of the event‐related potential. Additionally, we tested how clinical measures related to these attentional markers. Results Subjectively, patients overestimated the frequency of negative pictures after nonpredictive cues. Patients, but not controls, showed upper α(10–12 Hz) suppression after nonpredictive and predictive negative cues relative to predictive neutral cues. Only patients showed increased P2 and decreased N2 amplitudes for pictures after nonpredictive cues, and, whereas both groups showed increased LPP amplitudes for pictures after nonpredictive cues, this modulation was more pronounced in OCD during the early LPP (<1,000 ms). In patients, P2 and LPP amplitudes for negative pictures were associated positively with anxiety and negatively with depression. Conclusions These results suggest that OCD patients process anticipation of inevitable and potential threat similarly and highlight the substantial motivational impact of uncertain events to OCD patients. Finally, the correlation with anxiety implies that anxiety represents the source of hypervigilance during uncertainty resolution.

  May 25, 2017   doi: 10.1002/da.22655   open full text
• Are there sensitive periods when child maltreatment substantially elevates suicide risk? Results from a nationally representative sample of adolescents.
  Stephanie H. Gomez, Jenny Tse, Yan Wang, Brianna Turner, Alexander J. Millner, Matthew K. Nock, Erin C. Dunn.
  Depression and Anxiety. May 23, 2017
  Background Although child maltreatment is a well documented risk factor for suicidal behavior, little is known about whether the timing of child maltreatment differentially associates with risk of suicidal ideation, suicide plans, or suicide attempts. The goal of this study was to examine whether a first exposure to physical or sexual abuse during specific developmental periods significantly elevated risk for suicidal behavior in adolescents. Methods Data came from the National Comorbidity Survey Adolescent Supplement, a population‐based sample of US adolescents aged 13–18 years old (n = 9,272). Using discrete time survival analysis, we assessed the association between timing of first abuse (early childhood: ages 0–5; middle childhood: ages 6–10; adolescence: ages 11–18) and suicidal ideation, plans, and attempts. Results Exposure to either physical or sexual abuse increased the odds of reporting suicidal ideation (odds ratio [OR] = 5.06 and OR = 3.56, respectively), plans (OR = 3.63 and OR = 3.58, respectively), and attempts (OR = 5.80 and OR = 4.21, respectively), even after controlling for sociodemographic covariates and psychiatric disorders. However, the timing of physical and sexual abuse exposure was unassociated with suicidal behavior (all p values >.05). Conclusions Exposure to child maltreatment is strongly associated with risk for adolescent suicidal behaviors, though this association did not vary based on the developmental timing of first exposure. These findings suggest that prevention efforts should be implemented throughout early development and target all children, regardless of when they were first exposed.

  May 23, 2017   doi: 10.1002/da.22650   open full text
• The experience sampling method as an mHealth tool to support self‐monitoring, self‐insight, and personalized health care in clinical practice.
  Jim Os, Simone Verhagen, Anne Marsman, Frenk Peeters, Maarten Bak, Machteld Marcelis, Marjan Drukker, Ulrich Reininghaus, Nele Jacobs, Tineke Lataster, Claudia Simons, , Richel Lousberg, Sinan Gülöksüz, Carsten Leue, Peter C. Groot, Wolfgang Viechtbauer, Philippe Delespaul.
  Depression and Anxiety. May 23, 2017
  Background The experience sampling method (ESM) builds an intensive time series of experiences and contexts in the flow of daily life, typically consisting of around 70 reports, collected at 8–10 random time points per day over a period of up to 10 days. Methods With the advent of widespread smartphone use, ESM can be used in routine clinical practice. Multiple examples of ESM data collections across different patient groups and settings are shown and discussed, varying from an ESM evaluation of a 6‐week randomized trial of mindfulness, to a twin study on emotion dynamics in daily life. Results Research shows that ESM‐based self‐monitoring and feedback can enhance resilience by strengthening the capacity to use natural rewards. Personalized trajectories of starting or stopping medication can be more easily initiated and predicted if sensitive feedback data are available in real time. In addition, personalized trajectories of symptoms, cognitive abilities, symptoms impacting on other symptoms, the capacity of the dynamic system of mental health to “bounce back” from disturbance, and patterns of environmental reactivity yield uniquely personal data to support shared decision making and prediction in clinical practice. Finally, ESM makes it possible to develop insight into previous implicit patterns of thought, experience, and behavior, particularly if rapid personalized feedback is available. Conclusions ESM enhances clinical practice and research. It is empowering, providing co‐ownership of the process of diagnosis, treatment evaluation, and routine outcome measurement. Blended care, based on a mix of face‐to‐face and ESM‐based outside‐the‐office treatment, may reduce costs and improve outcomes.

  May 23, 2017   doi: 10.1002/da.22647   open full text
• Latent structure of negative valence measures in childhood.
  Minyoung Lee, Steven H. Aggen, Dever M. Carney, Shannon Hahn, Elizabeth Moroney, Laura Machlin, Melissa A. Brotman, Kenneth E. Towbin, Ellen Leibenluft, Daniel S. Pine, Roxann Roberson‐Nay, John M. Hettema.
  Depression and Anxiety. May 22, 2017
  Background Internalizing disorders (IDs), consisting of the syndromes of anxiety and depression, are common, debilitating conditions often having onsets in adolescence. Scientists have developed dimensional self‐report instruments that assess putative negative valence system (NVS) trait‐like constructs as complimentary phenotypes to clinical symptoms. These include various measures that index temperamental predispositions to IDs and correlate with neural substrates of fear, anxiety, and affective regulation. This study sought to elucidate the overarching structure of putative NVS traits and their relationship to early manifestations of ID symptomatology. Methods The sample consisted of 768 juvenile twin subjects ages 9–13. Together with ID symptoms, extant validated instruments were chosen to assess a broad spectrum of NVS traits: anxiety sensitivity, irritability, fearfulness, behavioral activation and inhibition, and neuroticism and extraversion. Exploratory and confirmatory factor analyses (EFA/CFA) were used to investigate the latent structure of the associations among these different constructs and ID symptoms. Bifactor modeling in addition to standard correlated‐factor analytic approaches were applied. Results Factor analyses produced a primary tripartite solution comprising anxiety/fear, dysphoria, and positive affect among all these measures. Competing DSM‐like correlated factors and an RDoC‐like NVS bifactor structure provided similar fit to these data. Conclusions Our findings support the conceptual organization of a tripartite latent internalizing domain in developing children. This structure includes both clinical symptoms and a variety of self‐report dimensional traits currently in use by investigators. These various constructs are, therefore, most informatively investigated using an inclusive, integrated approach.

  May 22, 2017   doi: 10.1002/da.22656   open full text
• The efficacy of benzodiazepines as acute anxiolytics in children: A meta‐analysis.
  Heide Kuang, Jessica A. Johnson, Jilian M. Mulqueen, Michael H. Bloch.
  Depression and Anxiety. May 15, 2017
  Objective Current practice guidelines do not recommend benzodiazepines for acute management of anxiety disorders in pediatric patients. However, in procedural settings, benzodiazepines are commonly used to relieve acute preprocedural stress. This meta‐analysis examines the efficacy and tolerability of benzodiazepines as short‐term anxiolytics in children. Method PubMed was searched for randomized controlled trials assessing the efficacy of benzodiazepines as short‐term anxiolytics in pediatric patients. Twenty‐one trials involving 1,416 participants were included. A fixed effects model was used to examine the standardized mean difference of improvement in anxiety levels compared to control conditions. In stratified subgroup and meta‐regression, the effect of the specific agent, dose, timing, and setting of benzodiazepine treatment was examined. Results A significant benefit was seen for benzodiazepines compared to control (standardized mean difference = 0.71 [95% confidence interval, 0.60–0.82], k = 24, z = 12.7, P < .001). There was also funnel plot asymmetry in this meta‐analysis, suggesting some evidence of publication bias. Moderator analyses found that when benzodiazepines were used in dental or nonoperating room procedures, they were more effective than when they were used in operating room procedures (test for subgroup differences Q2 = 6.34, P = .04). Tolerability analysis revealed there was no significant difference in the risk of developing irritability or behavioral changes between benzodiazepine and control groups. Conclusions Benzodiazepines are effective and well‐tolerated when used as short‐term anxiolytics in procedural settings for pediatric patients. Further research is needed to determine whether benzodiazepines are effective in pediatric anxiety disorders.

  May 15, 2017   doi: 10.1002/da.22643   open full text
• Perceiving social pressure not to feel negative predicts depressive symptoms in daily life.
  Egon Dejonckheere, Brock Bastian, Eiko I. Fried, Sean C. Murphy, Peter Kuppens.
  Depression and Anxiety. May 12, 2017
  Background Western societies often overemphasize the pursuit of happiness, and regard negative feelings such as sadness or anxiety as maladaptive and unwanted. Despite this emphasis on happiness, the amount of people suffering from depressive complaints is remarkably high. To explain this apparent paradox, we examined whether experiencing social pressure not to feel sad or anxious could in fact contribute to depressive symptoms. Methods A sample of individuals (n = 112) with elevated depression scores (Patient Health Questionnaire [PHQ‐9] ≥ 10) took part in an online daily diary study in which they rated their depressive symptoms and perceived social pressure not to feel depressed or anxious for 30 consecutive days. Using multilevel VAR models, we investigated the temporal relation between this perceived social pressure and depressive symptoms to determine directionality. Results Primary analyses consistently indicated that experiencing social pressure predicts increases in both overall severity scores and most individual symptoms of depression, but not vice versa. A set of secondary analyses, in which we adopted a network perspective on depression, confirmed these findings. Using this approach, centrality analysis revealed that perceived social pressure not to feel negative plays an instigating role in depression, reflected by the high out‐ and low instrength centrality of this pressure in the various depression networks. Conclusions Together, these findings indicate how perceived societal norms may contribute to depression, hinting at a possible malignant consequence of society's denouncement of negative emotions. Clinical implications are discussed.

  May 12, 2017   doi: 10.1002/da.22653   open full text
• Low physical activity as a key differentiating factor in the potential high‐risk profile for depressive symptoms in older adults.
  Sofie Holmquist, Sabina Mattsson, Ingrid Schele, Peter Nordström, Anna Nordström.
  Depression and Anxiety. May 10, 2017
  Background The identification of potential high‐risk groups for depression is of importance. The purpose of the present study was to identify high‐risk profiles for depressive symptoms in older individuals, with a focus on functional performance. Methods The population‐based Healthy Ageing Initiative included 2,084 community‐dwelling individuals (49% women) aged 70. Explorative cluster analysis was used to group participants according to functional performance level, using measures of basic mobility skills, gait variability, and grip strength. Intercluster differences in depressive symptoms (measured by the Geriatric Depression Scale [GDS]‐15), physical activity (PA; measured objectively with the ActiGraph GT3X+), and a rich set of covariates were examined. Results The cluster analysis yielded a seven‐cluster solution. One potential high‐risk cluster was identified, with overrepresentation of individuals with GDS scores >5 (15.1 vs. 2.7% expected; relative risk = 6.99, P < .001); the prevalence of depressive symptoms was significantly lower in the other clusters (all P < .01). The potential high‐risk cluster had significant overrepresentations of obese individuals (39.7 vs. 17.4% expected) and those with type 2 diabetes (24.7 vs. 8.5% expected), and underrepresentation of individuals who fulfilled the World Health Organization's PA recommendations (15.6 vs. 59.1% expected; all P < .01), as well as low levels of functional performance. Conclusions The present study provided a potential high‐risk profile for depressive symptoms among elderly community‐dwelling individuals, which included low levels functional performance combined with low levels of PA. Including PA in medical screening of the elderly may aid in identification of potential high‐risk individuals for depressive symptoms.

  May 10, 2017   doi: 10.1002/da.22638   open full text
• Fear learning alterations after traumatic brain injury and their role in development of posttraumatic stress symptoms.
  Daniel E. Glenn, Dean T. Acheson, Mark A. Geyer, Caroline M. Nievergelt, Dewleen G. Baker, Victoria B. Risbrough,.
  Depression and Anxiety. May 10, 2017
  Background It is unknown how traumatic brain injury (TBI) increases risk for posttraumatic stress disorder (PTSD). One potential mechanism is via alteration of fear‐learning processes that could affect responses to trauma memories and cues. We utilized a prospective, longitudinal design to determine if TBI is associated with altered fear learning and extinction, and if fear processing mediates effects of TBI on PTSD symptom change. Methods Eight hundred fifty two active‐duty Marines and Navy Corpsmen were assessed before and after deployment. Assessments included TBI history, PTSD symptoms, combat trauma and deployment stress, and a fear‐potentiated startle task of fear acquisition and extinction. Startle response and self‐reported expectancy and anxiety served as measures of fear conditioning, and PTSD symptoms were measured with the Clinician‐Administered PTSD Scale. Results Individuals endorsing “multiple hit” exposure (both deployment TBI and a prior TBI) showed the strongest fear acquisition and highest fear expression compared to groups without multiple hits. Extinction did not differ across groups. Endorsing a deployment TBI was associated with higher anxiety to the fear cue compared to those without deployment TBI. The association of deployment TBI with increased postdeployment PTSD symptoms was mediated by postdeployment fear expression when recent prior‐TBI exposure was included as a moderator. TBI associations with increased response to threat cues and PTSD symptoms remained when controlling for deployment trauma and postdeployment PTSD diagnosis. Conclusions Deployment TBI, and multiple‐hit TBI in particular, are associated with increases in conditioned fear learning and expression that may contribute to risk for developing PTSD symptoms.

  May 10, 2017   doi: 10.1002/da.22642   open full text
• The role of family history of depression and the menopausal transition in the development of major depression in midlife women: Study of women's health across the nation mental health study (SWAN MHS).
  Alicia Colvin, Gale A. Richardson, Jill M. Cyranowski, Ada Youk, Joyce T. Bromberger.
  Depression and Anxiety. May 10, 2017
  Background This study evaluated whether family history of depression predicts major depression in midlife women above and beyond static risk factors (such as personal history of depression prior to midlife) and risks that may change dynamically across midlife (such as menopausal, psychosocial, and health profiles). Methods Participants were 303 African American and Caucasian women (42–52 years at baseline) recruited into the Study of Women's Health across the Nation (SWAN) Mental Health Study (MHS) in Pittsburgh. Major depression was assessed annually with Structured Clinical Interviews for DSM‐IV. Family mental health history was collected at the ninth or tenth annual follow‐up. Random effects logistic regression was used to assess the relationship between family history of depression and midlife depression, controlling for baseline sociodemographic characteristics and time‐varying risk factors. Results Family history of depression was associated with midlife depression after adjusting for participant's history of major depression prior to midlife, trait anxiety and baseline age, and time‐varying menopausal status, body mass index, very upsetting life events, and chronic difficulties (OR = 2.24, 95% CI = 1.17–4.29, P = .02). Higher odds of major depression were found when women were late perimenopausal or postmenopausal relative to when they were premenopausal or early perimenopausal (OR = 3.01, 95% CI = 1.76–5.15, P < .0001). However, menopausal status was only associated with major depression among women without a family history. Conclusions Family history of depression predicts major depression in midlife women independent of the menopausal transition and other time‐varying covariates. Notably, the menopausal transition was associated with increased risk only among women without a family history of depression.

  May 10, 2017   doi: 10.1002/da.22651   open full text
• Nicotine deprivation attenuates panic reactivity in smokers: Findings from a placebo‐controlled nicotine patch study.
  Kenneth Abrams, Sam Krimmel, Stacey Johnson, Kate Cieslowski, Helen Strnad, Arielle Melum, Caroline Kryder.
  Depression and Anxiety. May 10, 2017
  Background Prospective studies consistently find that smoking is a risk factor for the development of panic disorder (PD). A possible explanation is that nicotine deprivation promotes heightened sensitivity to bodily sensations and/or arterial carbon dioxide (CO2). Abrams et al. (2011) previously found that, in response to a CO2 rebreathing challenge, smokers experiencing more (vs. less) intense nicotine withdrawal had more severe panic symptoms and a stronger urge to escape. However, participants were aware of the last time they smoked, leaving unclear the extent to which fear reactivity was influenced by the pharmacologic effects of nicotine deprivation versus beliefs regarding when nicotine was most recently used. The present study aimed to ascertain whether nicotine deprivation, independent of beliefs regarding recent nicotine use, promotes fear reactivity among smokers. Methods Moderate to heavy smokers without PD (N = 25) participated in a placebo‐controlled, double‐blind study consisting of two sessions spaced 1 week apart. Participants abstained from nicotine for 2 hr prior to sessions. During one session participants were given a 21 mg nicotine replacement patch and, during the other, a placebo patch, with the order counterbalanced. For both sessions, after a 3‐hr absorption period, participants underwent a 10‐min CO2 rebreathing challenge. Results Wearing a nicotine (vs. placebo) patch increased self‐reported panic reactivity among participants, but did not significantly affect physiological and behavioral measures of reactivity. Conclusions In smokers without a history of PD, nicotine deprivation attenuates subjective panic reactivity. Possible explanations for the contrast between theory and laboratory findings as well as clinical implications are discussed.

  May 10, 2017   doi: 10.1002/da.22652   open full text
• Predictors of PTSD 40 years after combat: Findings from the National Vietnam Veterans longitudinal study.
  Maria M. Steenkamp, William E. Schlenger, Nida Corry, Clare Henn‐Haase, Meng Qian, Meng Li, Danny Horesh, Karen‐Inge Karstoft, Christianna Williams, Chia‐Lin Ho, Arieh Shalev, Richard Kulka, Charles Marmar.
  Depression and Anxiety. May 10, 2017
  Background Few studies have longitudinally examined predictors of posttraumatic stress disorder (PTSD) in a nationally representative sample of US veterans. We examined predictors of warzone‐related PTSD over a 25‐year span using data from the National Vietnam Veterans Longitudinal Study (NVVLS). Methods The NVVLS is a follow‐up study of Vietnam theater veterans (N = 699) previously assessed in the National Vietnam Veterans Readjustment Study (NVVRS), a large national‐probability study conducted in the late 1980s. We examined the ability of 22 premilitary, warzone, and postmilitary variables to predict current warzone‐related PTSD symptom severity and PTSD symptom change in male theater veterans participating in the NVVLS. Data included a self‐report Health Questionnaire survey and a computer‐assisted telephone Health Interview Survey. Primary outcomes were self‐reported PTSD symptoms assessed by the PTSD Checklist for DSM‐5 (PCL 5) and Mississippi PTSD Scale (M‐PTSD). Results Predictors of current PTSD symptoms most robust in hierarchical multivariable models were African‐American race, lower education level, negative homecoming reception, lower current social support, and greater past‐year stress. PTSD symptoms remained largely stable over time, and symptom exacerbation was predicted by African‐American race, lower education level, younger age at entry into Vietnam, greater combat exposure, lower current social support, and greater past‐year stressors. Conclusions Findings confirm the robustness of a select set of risk factors for warzone‐related PTSD, establishing that these factors can predict PTSD symptom severity and symptom change up to 40 years postdeployment.

  May 10, 2017   doi: 10.1002/da.22628   open full text
• Maternal choline status during pregnancy, but not that of betaine, is related to antenatal mental well‐being: The growing up in Singapore toward healthy outcomes cohort.
  Linde Lee, Phaik Ling Quah, Seang Mei Saw, Fabian K. P. Yap, Keith M. Godfrey, Yap Seng Chong, Michael J Meaney, Helen Chen, Mary Foong‐Fong Chong.
  Depression and Anxiety. May 04, 2017
  Background Choline and betaine status have previously been associated with symptoms of depression. However, the relation of maternal plasma choline and betaine concentrations in pregnancy to peripartum maternal mood is unknown. Methods Maternal plasma choline and betaine concentrations (μmol/L) were measured at 26–28 weeks gestation in the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother–offspring cohort. Participants completed the State‐Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EDPS) at 26–28 weeks gestation (n = 949) and at 3 months postnatal (n = 689): higher scores are indicative of more symptoms of anxiety and depression. Multivariate linear regression models were used to estimate the association of choline and betaine with ante‐ and postnatal mental well‐being adjusting for covariates. Results Mean (SD) antenatal plasma choline and betaine concentrations were 9.2 μmol/L (1.6) and 13.1 μmol/L (2.7), respectively. Plasma choline concentrations were positively associated with antenatal depressive (β = .24 EPDS score [95% CI: 0.05–0.43] per μmol/L] and anxiety symptoms (β = .46 STAI‐state score [95% CI: 0.03–0.88] per μmol/L) adjusting for covariates. Plasma betaine concentrations were not associated with antenatal depression or anxiety symptoms. No associations were observed between pregnancy choline or betaine and postnatal mental well‐being. Conclusion This study suggests that higher maternal plasma choline status during pregnancy is associated with more symptoms of antenatal depression and anxiety, whereas plasma betaine concentrations showed no associations. No associations were observed for postnatal mental well‐being. Prospective studies are required to replicate these findings and further examine the direction of causality and possible biological mechanisms.

  May 04, 2017   doi: 10.1002/da.22637   open full text
• Predicting suicide with the SAD PERSONS scale.
  Cara Katz, Jason R. Randall, Jitender Sareen, Dan Chateau, Randy Walld, William D. Leslie, JianLi Wang, James M. Bolton.
  Depression and Anxiety. May 04, 2017
  Background Suicide is a major public health issue, and a priority requirement is accurately identifying high‐risk individuals. The SAD PERSONS suicide risk assessment scale is widely implemented in clinical settings despite limited supporting evidence. This article aims to determine the ability of the SAD PERSONS scale (SPS) to predict future suicide in the emergency department. Methods Five thousand four hundred sixty‐two consecutive adults were seen by psychiatry consultation teams in two tertiary emergency departments with linkage to population‐based administrative data to determine suicide deaths within 6 months, 1, and 5 years. Results Seventy‐seven (1.4%) individuals died by suicide during the study period. When predicting suicide at 12 months, medium‐ and high‐risk scores on SPS had a sensitivity of 49% and a specificity of 60%; the positive and negative predictive values were 0.9 and 99%, respectively. Half of the suicides at both 6‐ and 12‐month intervals were classified as low risk by SPS at index visit. The area under the curve at 12 months for the Modified SPS was 0.59 (95% confidence interval [CI] range 0.51–0.67). High‐risk scores (compared to low risk) were significantly associated with death by suicide over the 5‐year study period using the SPS (hazard ratio 2.49; 95% CI 1.34–4.61) and modified version (hazard ratio 2.29; 95% CI 1.24–2.29). Conclusions Although widely used in educational and clinical settings, these findings do not support the use of the SPS and Modified SPS to predict suicide in adults seen by psychiatric services in the emergency department.

  May 04, 2017   doi: 10.1002/da.22632   open full text
• Between‐visit changes in suicidal ideation and risk of subsequent suicide attempt.
  Gregory E. Simon, Susan M. Shortreed, Eric Johnson, Arne Beck, Karen J. Coleman, Rebecca C. Rossom, Ursula S. Whiteside, Belinda H. Operskalski, Robert B. Penfold.
  Depression and Anxiety. April 25, 2017
  Background While clinicians are expected to routinely assess and address suicide risk, existing data provide little guidance regarding the significance of visit‐to‐visit changes in suicidal ideation. Methods Electronic health records from four large healthcare systems identified patients completing the Patient Health Questionnaire or PHQ9 at outpatient visits. For patients completing two questionnaires within 90 days, health system records and state vital records were used to identify nonfatal and fatal suicide attempts. Analyses examined how changes in PHQ9 item 9 responses between visits predicted suicide attempt or suicide death over 90 days following the second visit. Results Analyses included 430,701 pairs of item 9 responses for 118,696 patients. Among patients reporting thoughts of death or self‐harm “nearly every day” at the first visit, risk of suicide attempt after the second visit ranged from approximately 2.0% among those reporting continued thoughts “nearly every day” down to 0.5% among those reporting a decrease to “not at all.” Among those reporting thoughts of death or self‐harm “not at all” at the first visit, risk of suicide attempt following the second visit ranged from approximately 0.2% among those continuing to report such thoughts “not at all” up to 1.2% among those reporting an increase to “nearly every day”. Conclusions Resolution of suicidal ideation between visits does imply a clinically important reduction in short‐term risk, but prior suicidal ideation still implies significant residual risk. Onset of suicidal ideation between visits does not imply any special elevation compared to ongoing suicidal ideation. Risk is actually highest for patients repeatedly reporting thoughts of death or self‐harm.

  April 25, 2017   doi: 10.1002/da.22623   open full text
• Subjective and objective sleep quality modulate emotion regulatory brain function in anxiety and depression.
  Heide Klumpp, Julia Roberts, Mary C. Kapella, Amy E. Kennedy, Anand Kumar, K. Luan Phan.
  Depression and Anxiety. April 18, 2017
  Background Disturbances in emotion regulation and sleep are shared across anxiety and mood disorders. Poor sleep has been shown to impair cognitive processes which may undermine cognitive regulatory function. However, it remains unknown if sleep quality impacts regulatory mechanisms in clinical anxiety and depression. Methods During fMRI, 78 patients with social anxiety disorder, generalized anxiety disorder, and/or major depressive disorder completed a validated emotion regulation task, which involved reappraisal (i.e., decrease negative affect) as compared to viewing aversive images. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and actigraphy, representing subjective and objective measures of sleep, respectively. Regression analysis was conducted with the PSQI and actigraphy sleep efficiency, duration, and wake‐after sleep onset variables. Results PSQI and actigraphy measures indicated that the majority of patients experienced problematic sleep, however, subjective and objective sleep measures were uncorrelated. Whole‐brain voxel‐wise regression analysis, controlling for diagnosis, revealed worse self‐reported sleep corresponded with less reappraise‐related activation in the dorsal anterior cingulate cortex (DACC). The same analysis performed with actigraphy data showed less sleep efficiency positively corresponded with DACC activation. Post‐hoc stepwise regression analysis showed these sleep measures predicted DACC activity whereas anxiety and depression symptoms did not. Conclusions Individual differences in self‐perceived and objective sleep quality differentially modulated the DACC, which is implicated in cognitive reappraisal. Findings suggest neural correlates of emotion regulation tracks different aspects of the sleep experience. Results also indicate sleep disturbance may play a role in the emotion dysregulation observed in anxiety and depressive disorders.

  April 18, 2017   doi: 10.1002/da.22622   open full text
• The feasibility, acceptability, and outcomes of PRIME‐D: A novel mobile intervention treatment for depression.
  Danielle A. Schlosser, Timothy R. Campellone, Brandy Truong, Joaquin A. Anguera, Silvia Vergani, Sophia Vinogradov, Patricia Arean.
  Depression and Anxiety. April 18, 2017
  Background Despite decades of research and development, depression has risen from the fifth to the leading cause of disability in the United States. Barriers to progress in the field are (1) poor access to high‐quality care; (2) limited mental health workforce; and (3) few providers trained in the delivery of evidence‐based treatments (EBTs). Although mobile platforms are being developed to give consumers greater access to high‐quality care, too often these tools do not have empirical support for their effectiveness. In this study, we evaluated PRIME‐D, a mobile app intervention that uses social networking, goal setting, and a mental health coach to deliver text‐based, EBT's to treat mood symptoms and functioning in adults with depression. Methods Thirty‐six adults with depression remotely participated in PRIME‐D over an 8‐week period with a 4‐week follow‐up, with 83% retained over the 12‐week course of thestudy. Results On average, participants logged into the app 5 days/week. Depression scores (PHQ‐9) significantly improved over time (over 50% reduction), with coach interactions enhancing these effects. Mood‐related disability (Sheehan Disability Scale (SDS)) also significantly decreased over time with participants no longer being impaired by their mood symptoms. Overall use of PRIME‐D predicted greater gains in functioning. Improvements in mood and functioning were sustained over the 4‐week follow‐up. Conclusions Results suggest that PRIME‐D is a feasible, acceptable, and effective intervention for adults with depression and that a mobile service delivery model may address the serious public health problem of poor access to high‐quality mental health care.

  April 18, 2017   doi: 10.1002/da.22624   open full text
• Posttraumatic stress disorder and accelerated aging: PTSD and leukocyte telomere length in a sample of civilian women.
  Andrea L. Roberts, Karestan C. Koenen, Qixuan Chen, Paola Gilsanz, Susan M. Mason, Jennifer Prescott, Andrew Ratanatharathorn, Eric B. Rimm, Jennifer A. Sumner, Ashley Winning, Immaculata Vivo, Laura D. Kubzansky.
  Depression and Anxiety. April 05, 2017
  Background Studies in male combat veterans have suggested posttraumatic stress disorder (PTSD) is associated with shorter telomere length (TL). We examined the cross‐sectional association of PTSD with TL in women exposed to traumas common in civilian life. Methods Data are from a substudy of the Nurses’ Health Study II (N = 116). PTSD and subclinical PTSD were assessed in trauma‐exposed women using diagnostic interviews. An array of health behaviors and conditions were assessed. DNA was extracted from peripheral blood leukocytes (collected 1996–1999). Telomere repeat copy number to single gene copy number (T/S) was determined by quantitative real‐time PCR telomere assay. We used linear regression models to assess associations and examine whether a range of important health behaviors (e.g., cigarette smoking) and medical conditions (e.g., hypertension) previously associated with TL might explain a PTSD‐TL association. We further examined whether type of trauma exposure (e.g., interpersonal violence) was associated with TL and whether trauma type might explain a PTSD‐TL association. Results Relative to not having PTSD, women with a PTSD diagnosis had shorter log‐transformed TL (β = −.112, 95% confidence interval (CI) = −0.196, −0.028). Adjustment for health behaviors and medical conditions did not attenuate this association. Trauma type was not associated with TL and did not account for the association of PTSD with TL. Conclusions Our results add to growing evidence that PTSD may be associated with more rapid cellular aging as measured by telomere erosion. Moreover, the association could not be explained by health behaviors and medical conditions assessed in this study, nor by type of trauma exposure.

  April 05, 2017   doi: 10.1002/da.22620   open full text
• History of sexual trauma moderates psychotherapy outcome for posttraumatic stress disorder.
  John C. Markowitz, Yuval Neria, Karina Lovell, Page E. Meter, Eva Petkova.
  Depression and Anxiety. April 04, 2017
  Background Moderators of differential psychotherapy outcome for posttraumatic stress disorder (PTSD) are rare, yet have crucial clinical importance. We tested the moderating effects of trauma type for three psychotherapies in 110 unmedicated patients with chronic DSM‐IV PTSD. Methods Patients were randomized to 14 weeks of prolonged exposure (PE, N = 38), interpersonal psychotherapy (IPT, N = 40), or relaxation therapy (RT, N = 32). The Clinician‐Administered PTSD Scale (CAPS) was the primary outcome measure. Moderator candidates were trauma type: interpersonal, sexual, physical. We fit a regression model for week 14 CAPS as a function of treatment (a three‐level factor), an indicator of trauma type presence/absence, and their interactions, controlling for baseline CAPS, and evaluated potential confounds. Results Thirty‐nine (35%) patients reported sexual, 68 (62%) physical, and 102 (93%) interpersonal trauma. Baseline CAPS scores did not differ by presence/absence of trauma types. Sexual trauma as PTSD criterion A significantly moderated treatment effect: whereas all therapies had similar efficacy among nonsexually‐traumatized patients, IPT had greater efficacy among sexually traumatized patients (efficacy difference with and without sexual trauma: IPT vs. PE and IPT vs. RT P’s < .05), specifically in PTSD symptom clusters B and D (P’s < .05). Conclusions Few studies have assessed effects of varying trauma types on effects of differing psychotherapies. In this exploratory study, sexual trauma moderated PTSD outcomes of three therapies: IPT showed greater benefit for sexually traumatized patients than PE or RT. The IPT focuses on affect to help patients determine trust in their current environments may particularly benefit patients who have suffered sexual assault.

  April 04, 2017   doi: 10.1002/da.22619   open full text
• Associations of childhood bullying victimization with lifetime suicidal behaviors among new U.S. Army soldiers.
  Laura Campbell‐Sills, Ronald C. Kessler, Robert J. Ursano, Anthony J. Rosellini, Tracie O. Afifi, Lisa J. Colpe, Steven G. Heeringa, Matthew K. Nock, Nancy A. Sampson, Jitender Sareen, Michael Schoenbaum, Xiaoying Sun, Sonia Jain, Murray B. Stein,.
  Depression and Anxiety. April 03, 2017
  Background Prior studies have documented associations of childhood bullying victimization with suicidal behaviors. However, many failed to adjust for concomitant risk factors and none investigated this relationship in military personnel. This study aimed to estimate independent associations of childhood bullying victimization with suicidal behaviors among U.S. Army soldiers. Methods Soldiers reporting for basic training completed a cross‐sectional survey assessing mental disorders, suicidal behaviors, and childhood adversities including two types of bullying victimization: (1) Physical Assault/Theft and (2) Bullying Comments/Behaviors. Associations of childhood bullying experiences with suicidal behaviors were estimated using discrete‐time survival analysis of person–year data from 30,436 soldiers. Models adjusted for sociodemographic factors, childhood maltreatment by adults, and mental disorders. Results After comprehensive adjustment for other risk factors, more frequent Physical Assault/Theft by peers during childhood was associated with increased odds of lifetime suicidal ideation (adjusted odds ratio [AOR] = 1.18, 95% CI: 1.11–1.26, P < .001) and attempt (AOR = 1.30, 95% CI: 1.13‐1.50, P < .001). More frequent Bullying Comments/Behaviors were associated with increased risk of ideation (AOR = 1.30, 95% CI: 1.26‐1.35, P < .001), plan (AOR = 1.44, 95% CI: 1.35‐1.54, P < .001), attempt (AOR = 1.24, 95% CI: 1.15‐1.33, P < .001), and onset of plan among ideators (AOR = 1.09, 95% CI: 1.03‐1.15, P = .002). Relative to no bullying victimization, exposure to the most persistent bullying was associated with two‐ to fourfold increase in risk for suicidal behaviors. Conclusions Childhood bullying victimization is associated with lifetime suicidal behaviors among new soldiers. Exposure to Bullying Comments/Behaviors during childhood is associated with progression from suicidal ideation to plan. Improved recognition of these relationships may inform risk mitigation interventions for soldiers.

  April 03, 2017   doi: 10.1002/da.22621   open full text
• Prevention of insulin resistance in adolescents at risk for type 2 diabetes with depressive symptoms: 1‐year follow‐up of a randomized trial.
  Lauren B. Shomaker, Nichole R. Kelly, Rachel M. Radin, Omni L. Cassidy, Lisa M. Shank, Sheila M. Brady, Andrew P. Demidowich, Cara H. Olsen, Kong Y. Chen, Eric Stice, Marian Tanofsky‐Kraff, Jack A. Yanovski.
  Depression and Anxiety. March 31, 2017
  Background Depression is associated with poor insulin sensitivity. We evaluated the long‐term effects of a cognitive behavioral therapy (CBT) program for prevention of depression on insulin sensitivity in adolescents at risk for type 2 diabetes (T2D) with depressive symptoms. Methods One‐hundred nineteen adolescent females with overweight/obesity, T2D family history, and mild‐to‐moderate depressive symptoms were randomized to a 6‐week CBT group (n = 61) or 6‐week health education (HE) control group (n = 58). At baseline, posttreatment, and 1 year, depressive symptoms were assessed, and whole body insulin sensitivity (WBISI) was estimated from oral glucose tolerance tests. Dual energy X‐ray absorptiometry assessed fat mass at baseline and 1 year. Primary outcomes were 1‐year changes in depression and insulin sensitivity, adjusting for adiposity and other relevant covariates. Secondary outcomes were fasting and 2‐hr insulin and glucose. We also evaluated the moderating effect of baseline depressive symptom severity. Results Depressive symptoms decreased in both groups (P < .001). Insulin sensitivity was stable in CBT and HE (ΔWBISI: .1 vs. .3) and did not differ between groups (P = .63). However, among girls with greater (moderate) baseline depressive symptoms (N = 78), those in CBT developed lower 2‐hr insulin than those in HE (Δ‐16 vs. 16 μIU/mL, P < .05). Additional metabolic benefits of CBT were seen for this subgroup in post hoc analyses of posttreatment to 1‐year change. Conclusions Adolescent females at risk for T2D decreased depressive symptoms and stabilized insulin sensitivity 1 year following brief CBT or HE. Further studies are required to determine if adolescents with moderate depression show metabolic benefits after CBT.

  March 31, 2017   doi: 10.1002/da.22617   open full text
• Moral injury in U.S. combat veterans: Results from the national health and resilience in veterans study.
  Blair E. Wisco, Brian P. Marx, Casey L. May, Brenda Martini, John H. Krystal, Steven M. Southwick, Robert H. Pietrzak.
  Depression and Anxiety. March 29, 2017
  Background Combat exposure is associated with increased risk of mental disorders and suicidality. Moral injury, or persistent effects of perpetrating or witnessing acts that violate one's moral code, may contribute to mental health problems following military service. The pervasiveness of potentially morally injurious events (PMIEs) among U.S. combat veterans, and what factors are associated with PMIEs in this population remains unknown. Methods Data were analyzed from the National Health and Resilience in Veterans Study (NHRVS), a contemporary and nationally representative survey of a population‐based sample of U.S. veterans, including 564 combat veterans, collected September–October 2013. Types of PMIEs (transgressions by self, transgressions by others, and betrayal) were assessed using the Moral Injury Events Scale. Psychiatric and functional outcomes were assessed using established measures. Results A total of 10.8% of combat veterans acknowledged transgressions by self, 25.5% endorsed transgressions by others, and 25.5% endorsed betrayal. PMIEs were moderately positively associated with combat severity (β = .23, P < .001) and negatively associated with white race, college education, and higher income (βs = .11–.16, Ps < .05). Transgressions by self were associated with current mental disorders (OR = 1.65, P < .001) and suicidal ideation (OR = 1.67, P < .001); betrayal was associated with postdeployment suicide attempts (OR = 1.99, P < .05), even after conservative adjustment for covariates, including combat severity. Conclusions A significant minority of U.S combat veterans report PMIEs related to their military service. PMIEs are associated with risk for mental disorders and suicidality, even after adjustment for sociodemographic variables, trauma and combat exposure histories, and past psychiatric disorders.

  March 29, 2017   doi: 10.1002/da.22614   open full text
• PTSD and cognitive symptoms relate to inhibition‐related prefrontal activation and functional connectivity.
  Ashley N. Clausen, Alex J. Francisco, Joan Thelen, Jared Bruce, Laura E. Martin, Joan McDowd, W. Kyle Simmons, Robin L. Aupperle.
  Depression and Anxiety. March 29, 2017
  Background Posttraumatic stress disorder (PTSD) is associated with reduced executive functioning and verbal memory performance, as well as abnormal task‐specific activity in prefrontal cortex (PFC) and anterior cingulate cortices (ACC). The current study examined how PTSD symptoms and neuropsychological performance in combat veterans relates to (1) medial PFC and ACC activity during cognitive inhibition, and (2) task‐independent PFC functional connectivity. Methods Thirty‐nine male combat veterans with varying levels of PTSD symptoms completed the multisource interference task during functional magnetic resonance imaging. Robust regression analyses were used to assess relationships between percent signal change (PSC: incongruent–congruent) and both PTSD severity and neuropsychological performance. Analyses were conducted voxel‐wise and for PSC extracted from medial PFC and ACC regions of interest. Resting‐state scans were available for veterans with PTSD. Regions identified via task‐based analyses were used as seeds for resting‐state connectivity analyses. Results Worse PTSD severity and neuropsychological performance related to less medial PFC and rostral ACC activity during interference processing, driven partly by increased activation to congruent trials. Worse PTSD severity related to reduced functional connectivity between these regions and bilateral, lateral PFC (Brodmann area 10). Worse neuropsychological performance related to reduced functional connectivity between these regions and the inferior frontal gyrus. Conclusions PTSD and associated neuropsychological deficits may result from difficulties regulating medial PFC regions associated with “default mode,” or self‐referential processing. Further clarification of functional coupling deficits between default mode and executive control networks in PTSD may enhance understanding of neuropsychological and emotional symptoms and provide novel treatment targets.

  March 29, 2017   doi: 10.1002/da.22613   open full text
• The predictive value of dorsal cingulate activity and fractional anisotropy on long‐term PTSD symptom severity.
  Mitzy Kennis, PhD, Sanne J. H. Rooij, PhD, Alieke Reijnen, MSc, Elbert Geuze, PhD.
  Depression and Anxiety. March 15, 2017
  Background Posttraumatic stress disorder (PTSD) can be treated with trauma‐focused therapy, although only about 50% of the patients recover on the short‐term. In order to improve response rates it is important to identify who will and will not recover from trauma‐focused therapy. Although previous studies reported dorsal anterior cingulate cortex (ACC) activity, as well as dorsal cingulum bundle white matter microstructure integrity as markers for the persistence of PTSD symptoms on the short‐term, it remains unclear whether these markers also predict long‐term PTSD symptom severity. Methods PTSD patients (n = 57) were investigated with clinical interviews and an MRI protocol before the start of treatment. Clinical interviews were repeated after 6–8 months of treatment (short‐term follow‐up), and on average 4 years later (long‐term follow‐up). Twenty‐eight PTSD patients returned for the long‐term follow‐up. Dorsal ACC activity in response to negative images, and fractional anisotropy (FA) of the dorsal cingulum were the neural markers investigated. Results In this long‐term follow‐up sample (n = 28), dorsal ACC activity and dorsal cingulum FA values significantly predicted CAPS scores on short‐ and long‐term follow‐up. The results remained significant after controlling for baseline CAPS score, early trauma, and comorbidity. Conclusion This study confirms the importance of the cingulate cortex activation and white matter integrity not only for short‐term treatment outcome, but also for PTSD long‐term symptom severity. Future treatments should target ACC function in particular during treatment in order to improve response rates.

  March 15, 2017   doi: 10.1002/da.22605   open full text
• Ultra‐brief behavioral skills trainings for blood injection injury phobia.
  Alicia E. Meuret, Erica Simon, Lavanya Bhaskara, Thomas Ritz.
  Depression and Anxiety. March 15, 2017
  Background Blood injection injury (BII) phobia is common, with debilitating consequences to the health and well being of many of its sufferers. BII phobia presents with a unique fear response that can involve drops in blood pressure and ultimately fainting. The aim of this study was to provide proof of concept for a line of brief, easy to implement, video‐based interventions for reducing phobic avoidance and fears in BII sufferers. One of the interventions was a novel Hypoventilation Respiratory Training (HRT) aimed at reducing the exaggerated ventilation response (hyperventilation) seen in BII phobia. The response has been linked to cerebral vasoconstriction and fainting symptoms. Method Sixty BII patients were randomly assigned to one of three 12‐min video‐guided trainings: Symptom‐Associated Tension (SAT) training, Relaxation Skills Training (RST), or HRT. Experiential and cardiorespiratory activity to phobic stimuli was assessed before and after training. Results Both SAT and HRT resulted in overall greater reductions of phobic fears and symptoms than RST. SAT significantly increased heart rate during exposure, and HRT led to significantly reduced ventilation, increases in PCO2, and elevated blood pressure throughout exposure and recovery. Treatment expectancy was rated equally high across conditions, whereas credibility ratings were highest for HRT. Conclusions Brief, video‐based instructions in muscle tension and normocapnic breathing are effective in reducing BII symptom severity and require minimal time and expertise. HRT may be particularly helpful in reducing fainting caused by cerebral vasoconstriction.

  March 15, 2017   doi: 10.1002/da.22616   open full text
• Disruption of white matter structural integrity and connectivity in posttraumatic stress disorder: A TBSS and tractography study.
  Elizabeth A. Olson, Jiaolong Cui, Rena Fukunaga, Lisa D. Nickerson, Scott L. Rauch, Isabelle M. Rosso.
  Depression and Anxiety. March 15, 2017
  Background Most studies of brain white matter (WM) in posttraumatic stress disorder (PTSD) have focused on combat trauma, and often were confounded by neurological and substance dependence comorbidity. This study used tract‐based spatial statistics (TBSS) and probabilistic tractography to characterize WM microstructure in a mixed‐sex community sample of PTSD patients exposed to diverse and multiple traumas, and in trauma‐exposed normal comparison (TENC) subjects. Methods TBSS compared diffusion measures between 20 adults with DSM‐IV PTSD and 17 TENC, using a whole‐brain voxel‐wise approach. Probabilistic tractography using Freesurfer's TRACULA was employed to measure diffusion tensor imaging (DTI) metrics within anatomically defined pathways. DTI metrics were compared between groups and correlated with PTSD symptom severity and trauma load. Results Controlling for age, sex, and motion, PTSD subjects had significantly reduced fractional anisotropy (FA) in a left frontal lobe cluster compared with TENC, at p < .05, family‐wise error corrected. Tractography identified significant group differences in the inferior longitudinal fasciculus (ILF), including lower FA and higher radial diffusivity in PTSD compared with TENC. Within the PTSD group, FA values were not correlated with symptom severity or trauma load. Results remained significant after removing participants using psychotropic medication or those with comorbid major depression. Conclusions PTSD patients had reduced WM integrity in left hemisphere frontal WM and temporal‐occipital WM tracts, compared to trauma‐exposed controls. Reduced frontal FA is consistent with compromised top‐down attentional control and emotion regulation in PTSD, while reduced ILF FA may be related to sensory processing and gating abnormalities in this disorder.

  March 15, 2017   doi: 10.1002/da.22615   open full text
• Mobile assessment of heightened skin conductance in posttraumatic stress disorder.
  Rebecca Hinrichs, Vasiliki Michopoulos, Sterling Winters, Alex O. Rothbaum, Barbara O. Rothbaum, Kerry J. Ressler, Tanja Jovanovic.
  Depression and Anxiety. February 21, 2017
  Background Increased psychophysiological reactivity is a hallmark intermediate phenotype of posttraumatic stress disorder (PTSD). Individuals with PTSD exhibit greater skin conductance (SC) responses to trauma scripts than trauma survivors without PTSD. However, trauma scripts require time for development and cannot be easily used in a single visit. Thus, there is a need for a low‐cost, easy‐to‐use, SC recording protocol for PTSD assessment. Methods Using a mobile device (eSense) connected to a portable tablet computer, we assessed SC reactivity to a standard trauma interview (STI) in 63 participants recruited from Grady Memorial Hospital in Atlanta, GA, approximately 1 year after trauma exposure. SC response (SCR) was calculated by subtracting the SC level (SCL) at the end of the baseline recording from the maximum SCL during the STI. Results SCL was significantly higher during the STI compared to baseline (P < .001), and individuals with PTSD showed significantly greater SCR than individuals without PTSD (P = .006). Logistic regression using SCR with PTSD diagnosis as the outcome showed an odds ratio of 1.76 (95% CI: 1.11–2.78). Lastly, higher SCR during the STI was also significantly associated with PTSD symptom total score controlling for demographics and trauma severity (b = 0.42, P = .001). Conclusions The current study demonstrated feasibility of the use of a mobile device for assessing psychophysiological reactivity in those with PTSD. The use of this low‐cost, easy‐to‐use mobile device to collect objective physiological data in concert with a STI can be easily disseminated in clinical and research settings.

  February 21, 2017   doi: 10.1002/da.22610   open full text
• Technology to train the brain: Pushing methodology and treatment in the scientific research symposium 2016.
  Sheila A. M. Rauch.
  Depression and Anxiety. February 18, 2017
  There is no abstract available for this paper.

  February 18, 2017   doi: 10.1002/da.22611   open full text
• Depression care among depressed adults with and without comorbid substance use disorders in the United States.
  Beth Han, Mark Olfson, Ramin Mojtabai.
  Depression and Anxiety. February 02, 2017
  Objective We compared the prevalence of receiving depression care between adults with past‐year major depressive episodes (depressed) and substance use disorders (SUD) in the United States and their depressed counterparts without SUD. Method Data were from 25,500 adults who participated in the 2008–2014 National Surveys on Drug Use and Health. Descriptive analyses and logistic regression models were applied. Results During 2008–2014, approximately 55.4% of depressed U.S. adults with SUD received past‐year depression care, while 60.1% of depressed adults without SUD received such care. Overall, co‐occurring SUD was associated with an 8% decreased likelihood of receiving past‐year depression care (risk ratio (RR) = 0.92, 95% CI = 0.89–0.96). For depressed adults with severe functional impairment, co‐occurring SUD was associated with a 9% decreased likelihood of receiving past‐year depression care (RR = 0.91, 95% CI = 0.87–0.95). For depressed men, co‐occurring SUD was associated with a 13% decreased likelihood of receiving past‐year depression care (RR = 0.87, 95% CI = 0.81–0.94). The following depressed adults were at increased risk of not receiving depression care: those without functional impairment, without suicidal ideation, and without physical comorbidities, aged 18–29, male, racial/ethnic minorities, having less than high school education, uninsured, and never married. Conclusions Among depressed adults in the United States, comorbid SUD modestly but significantly decreases the likelihood of receiving past‐year depression care. Depressed young adults, men, racial/ethnic minorities, less educated individuals, uninsured adults, and never married adults are also at increased risk for not receiving depression care. Outreach efforts are needed to broaden access to depression care for these underserved adults.

  February 02, 2017   doi: 10.1002/da.22592   open full text
• Age of onset and family history as indicators of polygenic risk for major depression.
  Anna R. Docherty, Alexis C. Edwards, Fuzhong Yang, Roseann E. Peterson, Chelsea Sawyers, Daniel E. Adkins, Ashlee A. Moore, Bradley T. Webb, Silviu A. Bacanu, Jonathan Flint, Kenneth S. Kendler.
  Depression and Anxiety. February 02, 2017
  Background The extent to which earlier age of onset (AO) is a reflection of increased genetic risk for major depression (MD) is still unknown. Previous biometrical research has provided mixed empirical evidence for the genetic overlap of AO with MD. If AO is demonstrated to be relevant to molecular polygenic risk for MD, incorporation of AO as a phenotype could enhance future genetic studies. Methods This research estimated the SNP‐based heritability of AO in the China, Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) case‐control sample (N = 9,854; MD case, n = 4,927). Common single nucleotide polymorphism heritability of MD was also examined across both high and low median‐split AO groups, and best linear unbiased predictor (BLUP) scores of polygenic risk, in split‐halves, were used to predict AO. Distributions of genetic risk across early and late AO were compared, and presence of self‐reported family history (FH) of MD was also examined as a predictor of AO. Results AO was not significantly heritable and polygenic risk derived from the aggregated effects of common genetic variants did not significantly predict AO in any analysis. AO was modestly but significantly lower in cases with a first‐degree genetic FH of MD. Conclusions Findings indicate that AO is associated with greater self‐reported genetic risk for MD in cases, yet not associated with common variant polygenic risk for MD. Future studies of early MD may benefit more from the examination of important moderating variables such as early life events.

  February 02, 2017   doi: 10.1002/da.22607   open full text
• Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year.
  Aimee R. Kroll‐Desrosiers, Benjamin C. Nephew, Jessica A. Babb, Yurima Guilarte‐Walker, Tiffany A. Moore Simas, Kristina M. Deligiannidis.
  Depression and Anxiety. January 30, 2017
  Background Due to its potent effects on social behavior, including maternal behavior, oxytocin has been identified as a potential mediator of postpartum depression and anxiety. The objective of this study was to examine the relationship between peripartum synthetic oxytocin administration and the development of depressive and anxiety disorders within the first year postpartum. We hypothesized that women exposed to peripartum synthetic oxytocin would have a reduced risk of postpartum depressive and anxiety disorders compared with those without any exposure. Methods Population‐based data available through the Massachusetts Integrated Clinical Academic Research Database (MiCARD) were used to retrospectively (2005–2014) examine this relationship and calculate the relative risk of peripartum synthetic oxytocin for the development of postpartum depressive and anxiety disorders in exposed (n = 9,684) compared to unexposed (n = 37,048) deliveries. Results Among deliveries to women with a history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 36% (relative risk (RR): 1.36; 95% confidence interval (95% CI): 1.20–1.55). In deliveries to women with no history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 32% compared to those not exposed (RR: 1.32; 95% CI: 1.23‐1.42). Conclusions Contrary to our hypothesis, results indicate that women with peripartum exposure to synthetic oxytocin had a higher relative risk of receiving a documented depressive or anxiety disorder diagnosis or antidepressant/anxiolytic prescription within the first year postpartum than women without synthetic oxytocin exposure.

  January 30, 2017   doi: 10.1002/da.22599   open full text
• Nonsteroidal anti‐inflammatory drugs (NSAIDs) and paracetamol do not affect 6‐month mood‐stabilizing treatment outcome among 482 patients with bipolar disorder.
  Ole Köhler‐Forsberg, Louisa Sylvia, Michael Thase, Joseph R. Calabrese, Thilo Deckersbach, Mauricio Tohen, Charles L. Bowden, Melvin McInnis, James H. Kocsis, Edward S. Friedman, Terence A. Ketter, Susan McElroy, Richard C. Shelton, Andrew A. Nierenberg.
  Depression and Anxiety. January 30, 2017
  Background Many mood disorder patients need analgesics due to increased pain sensitivity. Recent studies have suggested that nonsteroidal anti‐inflammatory drugs (NSAIDs) may inhibit antidepressant treatment, which requires replication before clinical recommendations. Methods The Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study randomized participants to 6 months lithium or quetiapine treatment. Use of NSAIDs and paracetamol was assessed throughout the study period and psychopathology measured with the Clinical Global Impression Scale for Bipolar Disorder (CGI‐BP) and Bipolar Inventory of Symptoms Scale (BISS). The effects of NSAIDs and paracetamol on treatment outcome were examined using mixed effects linear regression adjusted for age, gender, body mass index, smoking status, exercise, and somatic diseases. Results Among 482 participants, 177 (36.7%) used NSAIDs and/or paracetamol during the study. NSAID and paracetamol users did not differ from nonusers with respect to treatment outcome with lithium or quetiapine at any time point during 6 months treatment on the overall CGI‐BP (β = 0.001 (95% CI = −0.01 to −0.01), P = .87), the BISS (β = 0.01 (95% CI = −0.17 to 0.15), P = .91), nor the CGI‐BP subscales for depression or mania. Users of NSAIDs only (n = 76), paracetamol only (n = 62), and users of both NSAIDs and paracetamol (n = 39) showed no statistical difference compared to nonusers (all P > .3). Conclusions This is the first trial to show that use of NSAIDs and paracetamol, alone or in combination, does not affect lithium‐ or quetiapine‐based bipolar disorder mood‐stabilizing treatment outcomes. Prior studies have suggested that NSAIDs may inhibit antidepressant treatment, whereas our results support findings indicating no detrimental effects of NSAIDs or paracetamol on affective disorder treatment.

  January 30, 2017   doi: 10.1002/da.22601   open full text
• Acute stress disorder and the transition to posttraumatic stress disorder in children and adolescents: Prevalence, course, prognosis, diagnostic suitability, and risk markers.
  Richard Meiser‐Stedman, Anna McKinnon, Clare Dixon, Adrian Boyle, Patrick Smith, Tim Dalgleish.
  Depression and Anxiety. January 30, 2017
  Background Early recovery from trauma exposure in youth is poorly understood. This prospective longitudinal study examined the early course of traumatic stress responses in recently trauma‐exposed youth, evaluated the revised DSM‐5 acute stress disorder (ASD) and PTSD diagnoses and alternative diagnoses, and identified risk factors for persistent traumatic stress. Method Participants were 8‐ to 17‐year‐old emergency departments attendees exposed to single incident traumas. Structured clinical interviews were undertaken at 2 (n = 226) and 9 weeks (n = 208) posttrauma. Results Using the revised criteria in DSM‐5, 14.2% met criteria for ASD at week 2 and 9.6% met criteria for PTSD at week 9. These prevalences were similar to the corresponding DSM‐IV diagnoses (18.6% ASD at week 2; 8.7% PTSD at week 9). Using the same diagnostic criteria (DSM‐IV or DSM‐5) across assessments (i.e., “2‐week PTSD”) suggested that caseness declined in prevalence by approximately half. Overlap between DSM‐IV and DSM‐5 ASD and DSM‐5 preschool child PTSD diagnoses was considerable. Two diagnoses were strongly predictive of corresponding week 9 diagnoses. Youth with ASD who subsequently had PTSD reported more negative alterations in cognition and mood at 2 weeks than those youth who did not develop PTSD. Conclusions Youth exposed to single‐event traumas experience considerable natural recovery in the first months posttrauma. Using DSM‐5 criteria, ASD may not capture all clinically significant traumatic stress in the acute phase and is only moderately sensitive for later PTSD. Future research needs to address the role and etiology of negative alterations in cognition and mood symptoms.

  January 30, 2017   doi: 10.1002/da.22602   open full text
• Relationship between the hippocampal shape abnormality and serum cortisol levels in first‐episode and drug‐naïve major depressive disorder patients.
  Rieko Watanabe, Shingo Kakeda, Keita Watanabe, Xiaodan Liu, Asuka Katsuki, Wakako Umeno‐Nakano, Hikaru Hori, Osamu Abe, Reiji Yoshimura, Yukunori Korogi.
  Depression and Anxiety. January 27, 2017
  Background We aimed to investigate the relationship between the hippocampal shape deformations and the serum cortisol levels in first‐episode and drug‐naïve major depression disorder (MDD) patients. Methods Thirty first‐episode and drug‐naïve MDD patients and 40 healthy subjects were recruited. High‐resolution T1‐weighted imaging and morning blood samples for cortisol measurement were obtained from all MDD patients and healthy subjects. In the hippocampal shape analysis, we compared the hippocampal shape between MDD patients and healthy subjects and evaluated the linear correlation between hippocampal shape deformations and the serum cortisol levels in MDD patients and healthy subjects. Results MDD patients showed significant inward deformations predominantly in the cornu ammonis (CA) 1 and subiculum in bilateral hippocampi compared to healthy subjects (false discovery rate (FDR) corrected, P < .05). Furthermore, in MDD patients, a significant linear correlation between inward deformations and high cortisol levels were found predominantly in the CA1 and subiculum, extending into the CA2–3 (FDR‐corrected, P < .05), whereas no significant linear correlation was observed in healthy subjects. Conclusions The serum cortisol levels are therefore considered to be associated with hippocampal shape abnormalities in MDD.

  January 27, 2017   doi: 10.1002/da.22604   open full text
• Symptoms of major depression: Their stability, familiality, and prediction by genetic, temperamental, and childhood environmental risk factors.
  Kenneth S. Kendler, Steven H. Aggen.
  Depression and Anxiety. January 25, 2017
  Background Psychiatry has long sought to develop biological diagnostic subtypes based on symptomatic differences. This effort assumes that symptoms reflect, with good fidelity, underlying etiological processes. We address this question for major depression (MD). Methods We examine, in twins from a population‐based registry, similarity in symptom endorsement in individuals meeting criteria for last‐year MD at separate interview waves and in concordant twin pairs. Among individuals with MD, we explore the impact of genetic‐temperamental and child adversity risk factors on individual reported symptoms. Aggregated criteria do not separate insomnia from hypersomnia, weight gain from loss, etc. while disaggregated criteria do. Results In twins with MD at two different waves, the mean tetrachoric correlations (±SEM) for aggregated and disaggregated DSM‐IV A criteria were, respectively, +0.31 ± 0.06 and +0.34 ± 0.03. In monozygotic (MZ) and dizygotic (DZ) twin pairs concordant for last‐year MD, the mean tetrachoric correlations for aggregated and disaggregated criteria were, respectively, +0.33 ± 0.07 and +0.43 ± 0.04, and +0.05 ± 0.08 and +0.07 ± 0.04. In individuals meeting MD criteria, neuroticism predicted the most MD symptoms (10), followed by childhood sexual abuse (8), low parental warmth (6), and genetic risk (4). Conclusions The correlations for individual depressive symptoms over multiple episodes and within MZ twins concordant for MD are modest suggesting the important role of transient influences. The multidetermination of individual symptoms was further evidenced by their prediction by personality and exposure to early life adversities. The multiple factors influencing symptomatic presentation in MD may contribute to our difficulties in isolating clinical depressive subtypes with distinct pathophysiologies.

  January 25, 2017   doi: 10.1002/da.22591   open full text
• Beliefs about the causes of depression and recovery and their impact on adherence, dosage, and successful tapering of antidepressants.
  Nicola S. Klein, Gerard D. Rijsbergen, Mascha C. ten Doesschate, Steven D. Hollon, Huibert Burger, Claudi L. H. Bockting.
  Depression and Anxiety. January 19, 2017
  Background Continuation of antidepressant medication (ADM) after remission is widely used to prevent depressive relapse/recurrence. Little is known about predictors of ADM use in terms of adherence, dosage, and successful tapering. The current study aimed to explore beliefs about the causes of depression and recovery (i.e., causal beliefs) and to examine whether they predict ADM use. Methods The data were drawn from a controlled trial and an extension of this trial with additional experience sampling. In total, 289 remitted patients with recurrent depression (ADM ≥ 6 months) were randomly assigned to Preventive Cognitive Therapy (PCT) with ADM tapering, PCT with maintenance ADM, or maintenance ADM alone. Adherence, ADM dosage, and causal beliefs regarding the first and last depressive episodes were explored via questionnaires. Results Most patients mentioned stressful life events as cause of depression, although more patients tended to endorse external causes for the first episode and internal causes for the last episode. ADM was most often mentioned as helpful during recovery from both episodes. Over half of all patients were adherent and under half of the patients in the tapering condition were able to complete the taper. Causal beliefs did not predict ADM use. Conclusions The results suggest that causal beliefs play little role in the use of maintenance ADM. More information is needed on factors contributing to successful tapering. The results must be interpreted with caution as this is not a naturalistic study and the results might be biased toward a more favorable view regarding ADM.

  January 19, 2017   doi: 10.1002/da.22598   open full text
• Stressful life events and catechol‐O‐methyl‐transferase (COMT) gene in bipolar disorder.
  Georgina M. Hosang, Helen L. Fisher, Sarah Cohen‐Woods, Peter McGuffin, Anne E. Farmer.
  Depression and Anxiety. January 19, 2017
  Background A small body of research suggests that gene–environment interactions play an important role in the development of bipolar disorder. The aim of the present study is to contribute to this work by exploring the relationship between stressful life events and the catechol‐O‐methyl‐transferase (COMT) Val158Met polymorphism in bipolar disorder. Methods Four hundred eighty‐two bipolar cases and 205 psychiatrically healthy controls completed the List of Threatening Experiences Questionnaire. Bipolar cases reported the events experienced 6 months before their worst depressive and manic episodes; controls reported those events experienced 6 months prior to their interview. The genotypic information for the COMT Val158Met variant (rs4680) was extracted from GWAS analysis of the sample. Results The impact of stressful life events was moderated by the COMT genotype for the worst depressive episode using a Val dominant model (adjusted risk difference = 0.09, 95% confidence intervals = 0.003–0.18, P = .04). For the worst manic episodes no significant interactions between COMT and stressful life events were detected. Conclusions This is the first study to explore the relationship between stressful life events and the COMT Val158Met polymorphism focusing solely on bipolar disorder. The results of this study highlight the importance of the interplay between genetic and environmental factors for bipolar depression.

  January 19, 2017   doi: 10.1002/da.22606   open full text
• The risk factors for postpartum depression: A population‐based study.
  Michael E. Silverman, Abraham Reichenberg, David A. Savitz, Sven Cnattingius, Paul Lichtenstein, Christina M. Hultman, Henrik Larsson, Sven Sandin.
  Depression and Anxiety. January 18, 2017
  Background Postpartum depression (PPD) can result in negative personal and child developmental outcomes. Only a few large population‐based studies of PPD have used clinical diagnoses of depression and no study has examined how a maternal depression history interacts with known risk factors. The objective of this study was to examine the impact of a depression history on PPD and pre‐ and perinatal risk factors. Methods A nationwide prospective cohort study of all women with live singleton births in Sweden from 1997 through 2008 was conducted. Relative risk (RR) of clinical depression within the first year postpartum and two‐sided 95% confidence intervals were estimated. Results The RR of PPD in women with a history of depression was estimated at 21.03 (confidence interval: 19.72–22.42), compared to those without. Among all women, PPD risk increased with advanced age (1.25 (1.13–1.37)) and gestational diabetes (1.70 (1.36–2.13)). Among women with a history of depression, pregestational diabetes (1.49 (1.01–2.21)) and mild preterm delivery also increased risk (1.20 (1.06–1.36)). Among women with no depression history, young age (2.14 (1.79–2.57)), undergoing instrument‐assisted (1.23 (1.09–1.38)) or cesarean (1.64(1.07–2.50)) delivery, and moderate preterm delivery increased risk (1.36 (1.05–1.75)). Rates of PPD decreased considerably after the first postpartum month (RR = 0.27). Conclusion In the largest population‐based study to date, the risk of PPD was more than 20 times higher for women with a depression history, compared to women without. Gestational diabetes was independently associated with a modestly increased PPD risk. Maternal depression history also had a modifying effect on pre‐ and perinatal PPD risk factors.

  January 18, 2017   doi: 10.1002/da.22597   open full text
• An examination of the etiologic overlap between the genetic and environmental influences on insomnia and common psychopathology.
  Mackenzie J. Lind, Sage E. Hawn, Christina M. Sheerin, Steven H. Aggen, Robert M. Kirkpatrick, Kenneth S. Kendler, Ananda B. Amstadter.
  Depression and Anxiety. January 16, 2017
  Background Insomnia is comorbid with internalizing and externalizing psychiatric disorders. However, the extent to which the etiologic influences on insomnia and common psychopathology overlap is unclear. There are limited genetically informed studies of insomnia and internalizing disorders and few studies of overlap exist with externalizing disorders. Methods We utilized twin data from the Virginia Adult Twin Studies of Psychiatric and Substance Use Disorders (total n = 7,500). Insomnia, internalizing disorders (major depressive disorder [MDD], generalized anxiety disorder [GAD]), and alcohol abuse or dependence (AAD) were assessed at two time points, while antisocial personality disorder (ASPD) was assessed once. Cholesky decompositions were performed in OpenMx and longitudinal measurement models were run on available phenotypes to reduce measurement error. Results The latent additive genetic influences on insomnia overlapped significantly (56% for females, 74% for males) with MDD and were shared completely (100%) with GAD. There was significant overlap of latent unique environmental influences, with overlap ranging from 38 to 100% across disorders. In contrast, there was less genetic overlap between insomnia and externalizing disorders, with 18% of insomnia's heritability shared with AAD and 23% with ASPD. Latent unique environmental overlap between insomnia and both externalizing disorders was negligible. Conclusions The evidence for substantial genetic overlap between insomnia and stable aspects of both internalizing disorders suggests that there may be few insomnia‐specific genes and investigation into unique environmental factors is important for understanding insomnia development. The modest overlap between insomnia and externalizing disorders indicates that these disorders are genetically related, but largely etiologically distinct.

  January 16, 2017   doi: 10.1002/da.22587   open full text
• Posttraumatic stress disorder symptoms and cognitive function in a large cohort of middle‐aged women.
  Jennifer A. Sumner, Kaitlin Hagan, Fran Grodstein, Andrea L. Roberts, Brian Harel, Karestan C. Koenen.
  Depression and Anxiety. January 10, 2017
  Background Posttraumatic stress disorder (PTSD) has been linked to cognitive decline, but research in women is generally lacking. We examined whether trauma and elevated PTSD symptoms were associated with worse cognitive function in middle‐aged civilian women. A secondary objective was to investigate the possible role of depression in the relation of PTSD symptoms to cognitive function. Methods The sample comprised 14,029 middle‐aged women in the Nurses’ Health Study II. Lifetime trauma exposure, lifetime PTSD symptoms, and past‐week depressive symptoms were measured in 2008. Cognitive function was measured in 2014–2016 using the Cogstate Brief Battery, a self‐administered online cognitive battery that assesses psychomotor speed, attention, learning, and working memory. We used linear regression models to estimate mean differences in cognition across PTSD symptom levels. Results Compared to no trauma, elevated PTSD symptoms consistent with probable PTSD (i.e., 4+ symptoms on a screening questionnaire) were associated with worse performance on psychomotor speed/attention (b = −0.08 standard units, p = .001) and learning/working memory (b = −0.09, p < .001) composites, after adjusting for sociodemographics. Although attenuated, associations remained significant when adjusted for depressive symptoms and other cognitive risk factors. We found the strongest associations among women with comorbid probable PTSD and depression. Conclusions PTSD symptoms were negatively related to measures of psychomotor speed/attention and learning/working memory in middle‐aged women. Our study adds to a growing literature that suggests that mental disorders are associated with worse cognitive function over the life course.

  January 10, 2017   doi: 10.1002/da.22600   open full text
• Depression impacts the physiological responsiveness of mother–daughter dyads during social interaction.
  Marlissa C. Amole, Jill M. Cyranowski, Aidan G. C. Wright, Holly A. Swartz.
  Depression and Anxiety. January 06, 2017
  Background Maternal depression is associated with increased risk of psychiatric illness in offspring. While risk may relate to depressed mothers’ difficulties regulating emotions in the context of interacting with offspring, physiological indicators of emotion regulation have rarely been examined during mother–child interactions—and never among mother–adolescent dyads in which both mother and adolescent have histories of major depressive disorder (MDD). Methods We examined changes in high‐frequency heart rate variability (HF‐HRV), an indicator of parasympathetic (vagal) function that has been related to depression, stress, social engagement, and emotion regulation, in 46 mother–daughter dyads (23 in which both mother and daughter had an MDD history and 23 never‐depressed controls). Hierarchical linear models evaluated changes in HF‐HRV while mother–daughter dyads engaged in discussions about shared pleasant events and relationship conflicts. Results While control dyads displayed positive slopes (increases) in HF‐HRV during both discussions, MDD dyads displayed minimal change in HF‐HRV across discussions. Among controls, HF‐HRV slopes were positively correlated between mothers and daughters during the pleasant events’ discussion. In contrast, HF‐HRV slopes were negatively correlated between MDD mothers and daughters during both discussions. Conclusions Vagal responses observed in control mother–daughter dyads suggest a pattern of physiological synchrony and reciprocal positive social engagement, which may play a role in adolescent development of secure social attachments and healthy emotion regulation. In contrast, MDD mothers and daughters displayed diminished and discordant patterns of vagal responsiveness. More research is needed to understand the development and consequences of these patterns of parasympathetic responses among depressed mother–daughter dyads.

  January 06, 2017   doi: 10.1002/da.22595   open full text
• Upregulating the positive affect system in anxiety and depression: Outcomes of a positive activity intervention.
  Charles T. Taylor, Sonja Lyubomirsky, Murray B. Stein.
  Depression and Anxiety. January 06, 2017
  Background Research suggests that the positive affect system may be an important yet underexplored treatment target in anxiety and depression. Existing interventions primarily target the negative affect system, yielding modest effects on measures of positive emotions and associated outcomes (e.g., psychological well‐being). The objective of the present pilot study was to evaluate the efficacy of a new transdiagnostic positive activity intervention (PAI) for anxiety and depression. Method Twenty‐nine treatment‐seeking individuals presenting with clinically impairing symptoms of anxiety and/or depression were randomly allocated to a 10‐session protocol comprised of PAIs previously shown in nonclinical samples to improve positive thinking, emotions, and behaviors (e.g., gratitude, acts of kindness, optimism; n = 16) or a waitlist (WL) condition (n = 13). Participants were assessed at pre‐ and posttreatment, as well as 3‐ and 6‐month follow‐up, on measures of positive and negative affect, symptoms, and psychological well‐being. ClinicalTrials.gov Identifier: NCT02330627 Results The PAI group displayed significantly larger improvements in positive affect and psychological well‐being from pre‐ to posttreatment compared to WL. Posttreatment and follow‐up scores in the PAI group were comparable to general population norms. The PAI regimen also resulted in significantly larger reductions in negative affect, as well as anxiety and depression symptoms, compared to WL. Improvements across all outcomes were large in magnitude and maintained over a 6‐month follow‐up period. Conclusions Targeting the positive affect system through a multicomponent PAI regimen may be beneficial for generating improvements in positive emotions and well‐being, as well as reducing negative affect and symptoms, in individuals with clinically impairing anxiety or depression.

  January 06, 2017   doi: 10.1002/da.22593   open full text
• Improving late life depression and cognitive control through the use of therapeutic video game technology: A proof‐of‐concept randomized trial.
  Joaquin A. Anguera, Faith M. Gunning, Patricia A. Areán.
  Depression and Anxiety. January 03, 2017
  Background Existing treatments for depression are known to have only modest effects, are insufficiently targeted, and are inconsistently utilized, particularly in older adults. Indeed, older adults with impaired cognitive control networks tend to demonstrate poor response to a majority of existing depression interventions. Cognitive control interventions delivered using entertainment software have the potential to not only target the underlying cerebral dysfunction associated with depression, but to do so in a manner that is engaging and engenders adherence to treatment protocol. Methods In this proof‐of‐concept trial (Clinicaltrials.gov #: NCT02229188), individuals with late life depression (LLD) (22; 60+ years old) were randomized to either problem solving therapy (PST, n = 10) or a neurobiologically inspired digital platform designed to enhance cognitive control faculties (Project: EVO™, n = 12). Given the overlapping functional neuroanatomy of mood disturbances and executive dysfunction, we explored the impact of an intervention targeting cognitive control abilities, functional disability, and mood in older adults suffering from LLD, and how those outcomes compare to a therapeutic gold standard. Results EVO participants demonstrated similar improvements in mood and self‐reported function after 4 weeks of treatment to PST participants. The EVO participants also showed generalization to untrained measures of working memory and attention, as well as negativity bias, a finding not evident in the PST condition. Individuals assigned to EVO demonstrated 100% adherence. Conclusions This study provides preliminary findings that this therapeutic video game targeting cognitive control deficits may be an efficacious LLD intervention. Future research is needed to confirm these findings.

  January 03, 2017   doi: 10.1002/da.22588   open full text
• Oxytocin response to youth–mother interactions in clinically anxious youth is associated with separation anxiety and dyadic behavior.
  Eli R. Lebowitz, Wendy K. Silverman, Alyssa M. Martino, Orna Zagoory‐Sharon, Ruth Feldman, James F. Leckman.
  Depression and Anxiety. January 03, 2017
  Background Anxiety disorders are common in youth and cause significant distress and impairment to the individual and family. Oxytocin (OT), a nine amino acid peptide, is implicated in anxiety regulation and modulation of close interpersonal and attachment behavior. Anxiety disorders have been linked to low levels of salivary OT in youth. Research has also linked oxytocinergic functioning to social support, warm contact, and bonding, and indicated that contact with attachment figures stimulates OT response. We examined OT response to a brief, positive youth–mother interaction in clinically anxious youth. We investigated whether quality of the youth–mother interaction as well as the presence of particular anxiety disorders, are associated with youth OT response. Method Salivary OT from 41 youth with primary DSM‐5 anxiety disorders was assayed before and after a 7‐min youth–mother interaction that was later systematically coded by two reliable coders. Youth and mothers also completed rating scales of youth anxiety symptoms. Results Affective touch, maternal sensitivity, maternal intrusiveness, youth engagement, and youth initiative all contributed significantly to predicting youth OT response. Repeated measures analyses showed that when affective touch was high youth had greater OT response. OT response was positively associated with the presence of separation anxiety disorder (SAD) and with child ratings of separation anxiety. Conclusions The findings highlight the importance of maternal and dyadic behavior patterns to oxytocinergic response in clinically anxious youth, shed light on the association between OT and SAD, and point to possible intervention strategies.

  January 03, 2017   doi: 10.1002/da.22585   open full text
• The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta‐analysis.
  John Moraros, Chijioke Nwankwo, Scott B. Patten, Darrell D. Mousseau.
  Depression and Anxiety. December 28, 2016
  Objective To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). Method We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. Results Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). Conclusions Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention.

  December 28, 2016   doi: 10.1002/da.22584   open full text
• Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.
  Xi Zhu, Liat Helpman, Santiago Papini, Franklin Schneier, John C. Markowitz, Page E. Meter, Martin A. Lindquist, Tor D. Wager, Yuval Neria.
  Depression and Anxiety. December 28, 2016
  Background Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD‐MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD‐MDD is associated with different network connectivity abnormalities than PTSD alone. Methods We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs‐FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD‐alone (n = 27), PTSD‐MDD (n = 21), and trauma‐exposed healthy controls (TEHCs, n = 34). Based on previous research, seeds included basolateral amygdala (BLA), centromedial amygdala (CMA), and nucleus accumbens (NAcc). Results Regardless of MDD comorbidity, PTSD was associated with decreased connectivity of BLA‐orbitalfrontal cortex (OFC) and CMA‐thalamus pathways, key to fear processing, and fear expression, respectively. PTSD‐MDD, compared to PTSD‐alone and TEHC, was associated with decreased connectivity across multiple amygdala and striatal‐subcortical pathways: BLA‐OFC, NAcc‐thalamus, and NAcc‐hippocampus. Further, while both the BLA‐OFC and the NAcc‐thalamus pathways were correlated with MDD symptoms, PTSD symptoms correlated with the amygdala pathways (BLA‐OFC; CMA‐thalamus) only. Conclusions Comorbid PTSD‐MDD may be associated with multifaceted functional connectivity alterations in both fear and reward systems. Clinical implications are discussed.

  December 28, 2016   doi: 10.1002/da.22594   open full text
• Internet‐based cognitive behavior therapy for major depressive disorder: A randomized controlled trial.
  Isabelle M. Rosso, William D.S. Killgore, Elizabeth A. Olson, Christian A. Webb, Rena Fukunaga, Randy P. Auerbach, Hannah Gogel, Jennifer L. Buchholz, Scott L. Rauch.
  Depression and Anxiety. December 23, 2016
  Background Prior research has shown that the Sadness Program, a technician‐assisted Internet‐based cognitive behavioral therapy (iCBT) intervention developed in Australia, is effective for treating major depressive disorder (MDD). The current study aimed to expand this work by adapting the protocol for an American population and testing the Sadness Program with an attention control group. Methods In this parallel‐group, randomized controlled trial, adult MDD participants (18–45 years) were randomized to a 10‐week period of iCBT (n = 37) or monitored attention control (MAC; n = 40). Participants in the iCBT group completed six online therapy lessons, which included access to content summaries and homework assignments. During the 10‐week trial, iCBT and MAC participants logged into the web‐based system six times to complete self‐report symptom scales, and a nonclinician technician contacted participants weekly to provide encouragement and support. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), and the secondary outcomes were the Patient Health Questionnaire‐9 and Kessler‐10. Results Intent‐to‐treat analyses revealed significantly greater reductions in depressive symptoms in iCBT compared with MAC participants, using both the self‐report measures and the clinician‐rated HRSD (d = −0.80). Importantly, iCBT participants also showed significantly higher rates of clinical response and remission. Exploratory analyses did not support illness severity as a moderator of treatment outcome. Conclusions The Sadness Program led to significant reductions in depression and distress symptoms. With its potential to be delivered in a scalable, cost‐efficient manner, iCBT is a promising strategy to enhance access to effective care.

  December 23, 2016   doi: 10.1002/da.22590   open full text
• Temporal discounting across three psychiatric disorders: Anorexia nervosa, obsessive compulsive disorder, and social anxiety disorder.
  Joanna E. Steinglass, Karolina M. Lempert, Tse‐Hwei Choo, Marcia B. Kimeldorf, Melanie Wall, B. Timothy Walsh, Abby J. Fyer, Franklin R. Schneier, H. Blair Simpson.
  Depression and Anxiety. December 23, 2016
  Background Temporal discounting refers to the tendency for rewards to lose value as the expected delay to receipt increases. Individuals with anorexia nervosa (AN) have been found to show reduced temporal discounting rates, indicating a greater preference for delayed rewards compared to healthy peers. Obsessive–compulsive disorder (OCD) and social anxiety disorder (SAD) commonly co‐occur with AN, and anxiety has been related to development and prognosis of AN. We examined whether reduced temporal discounting is present across these potentially related disorders, and explored the relationship between temporal discounting and anxiety transdiagnostically. Methods One hundred ninety six individuals (75 healthy controls (HC); 50 OCD; 27 AN; 44 SAD) completed two temporal discounting tasks in which they chose between smaller‐sooner and larger‐later monetary rewards. Two measures of discounting—discount rate and discount factor—were compared between diagnostic groups, and associations with anxious traits were examined. Results Individuals with AN showed decreased temporal discounting compared to HC. OCD and SAD groups did not differ significantly from HC. Across the sample, anxiety was associated with decreased discounting; more anxious individuals showed a greater preference for delayed reward. Conclusions We replicated the findings that individuals with AN show an increased preference for delayed reward relative to HC and that individuals with OCD do not differ from HC. We also showed that individuals with SAD do not differ from HC in discounting. Across this large sample, two measures of anxious temperament were associated with temporal discounting. These data raise new questions about the relationship between this dimensional trait and psychopathology.

  December 23, 2016   doi: 10.1002/da.22586   open full text
• Repeated trauma exposure does not impair distress reduction during imaginal exposure for posttraumatic stress disorder.
  Alissa B. Jerud, Frank J. Farach, Michele Bedard‐Gilligan, Hillary Smith, Lori A. Zoellner, Norah C. Feeny.
  Depression and Anxiety. December 06, 2016
  Background Based on experimental research on threat extinction, individuals exposed to repeated traumatic events may have impaired outcome in exposure therapy compared to those who have experienced a single trauma (Lang & McTeague, ). This study examined whether repeated trauma exposure predicts smaller changes in self‐reported distress during imaginal exposure and worse outcomes for patients with posttraumatic stress disorder (PTSD). Methods Adults (N = 116) with chronic PTSD received up to 10 sessions of prolonged exposure (PE) therapy. Trauma exposure was assessed via interview and number of traumatic events were summed for each participant. To examine reductions in distress during treatment, mean and peak values of distress during imaginal exposure were calculated for the first imaginal session (initial distress activation) and subsequent sessions (between‐session change in distress). Change in PTSD symptoms from pre‐ to posttreatment and follow‐up provided an additional index of outcome. Results In‐session distress during imaginal exposure decreased over the course of treatment. PTSD symptoms also decreased over treatment, with gains being maintained through follow‐up. Repeated trauma exposure was not significantly correlated with initial distress activation. Additionally, linear mixed‐model analyses showed no significant association between repeated trauma exposure and between‐session change in distress or PTSD symptoms. Conclusions Contrary to recent speculation, repeated trauma exposure did not predict less change in self‐reported distress during imaginal exposure or worse PTSD outcomes. The bench‐to‐bedside linkage of threat extinction to exposure therapy is discussed, noting strengths and weaknesses. Patients with repeated trauma exposure show reductions in distress with exposure treatment and benefit from PE as much as patients with single‐exposure trauma histories.

  December 06, 2016   doi: 10.1002/da.22582   open full text
• Melancholic and atypical depression as predictor and moderator of outcome in cognitive behavior therapy and pharmacotherapy for adult depression.
  Pim Cuijpers, Erica Weitz, Femke Lamers, Brenda W. Penninx, Jos Twisk, Robert J. DeRubeis, Sona Dimidjian, Boadie W. Dunlop, Robin B. Jarrett, Zindel V. Segal, Steven D. Hollon.
  Depression and Anxiety. December 06, 2016
  Background Melancholic and atypical depression are widely thought to moderate or predict outcome of pharmacological and psychological treatments of adult depression, but that has not yet been established. This study uses the data from four earlier trials comparing cognitive behavior therapy (CBT) versus antidepressant medications (ADMs; and pill placebo when available) to examine the extent to which melancholic and atypical depression moderate or predict outcome in an “individual patient data” meta‐analysis. Methods We conducted a systematic search for studies directly comparing CBT versus ADM, contacted the researchers, integrated the resulting datasets from these studies into one big dataset, and selected the studies that included melancholic or atypical depressive subtyping according to DSM‐IV criteria at baseline (n = 4, with 805 patients). After multiple imputation of missing data at posttest, mixed models were used to conduct the main analyses. Results In none of the analyses was melancholic or atypical depression found to significantly moderate outcome (indicating a better or worse outcome of these patients in CBT compared to ADM; i.e., an interaction), predict outcome independent of treatment group (i.e., a main effect), or predict outcome within a given modality. The outcome differences between patients with melancholia or atypical depression versus those without were consistently very small (all effect sizes g < 0.10). Conclusions We found no indication that melancholic or atypical depressions are significant or relevant moderators or predictors of outcome of CBT and ADM.

  December 06, 2016   doi: 10.1002/da.22580   open full text
• Posttraumatic stress disorder associated with unexpected death of a loved one: Cross‐national findings from the world mental health surveys.
  Lukoye Atwoli, Dan J. Stein, Andrew King, Maria Petukhova, Sergio Aguilar‐Gaxiola, Jordi Alonso, Evelyn J. Bromet, Giovanni Girolamo, Koen Demyttenaere, Silvia Florescu, Josep Maria Haro, Elie G. Karam, Norito Kawakami, Sing Lee, Jean‐Pierre Lepine, Fernando Navarro‐Mateu, Siobhan O'Neill, Beth‐Ellen Pennell, Marina Piazza, Jose Posada‐Villa, Nancy A. Sampson, Margreet ten Have, Alan M. Zaslavsky, Ronald C. Kessler,.
  Depression and Anxiety. December 06, 2016
  Background Unexpected death of a loved one (UD) is the most commonly reported traumatic experience in cross‐national surveys. However, much remains to be learned about posttraumatic stress disorder (PTSD) after this experience. The WHO World Mental Health (WMH) survey initiative provides a unique opportunity to address these issues. Methods Data from 19 WMH surveys (n = 78,023; 70.1% weighted response rate) were collated. Potential predictors of PTSD (respondent sociodemographics, characteristics of the death, history of prior trauma exposure, history of prior mental disorders) after a representative sample of UDs were examined using logistic regression. Simulation was used to estimate overall model strength in targeting individuals at highest PTSD risk. Results PTSD prevalence after UD averaged 5.2% across surveys and did not differ significantly between high‐income and low‐middle income countries. Significant multivariate predictors included the deceased being a spouse or child, the respondent being female and believing they could have done something to prevent the death, prior trauma exposure, and history of prior mental disorders. The final model was strongly predictive of PTSD, with the 5% of respondents having highest estimated risk including 30.6% of all cases of PTSD. Positive predictive value (i.e., the proportion of high‐risk individuals who actually developed PTSD) among the 5% of respondents with highest predicted risk was 25.3%. Conclusions The high prevalence and meaningful risk of PTSD make UD a major public health issue. This study provides novel insights into predictors of PTSD after this experience and suggests that screening assessments might be useful in identifying high‐risk individuals for preventive interventions.

  December 06, 2016   doi: 10.1002/da.22579   open full text
• Brain activation during fear extinction predicts exposure success.
  Tali Manber Ball, Sarah E. Knapp, Martin P. Paulus, Murray B. Stein.
  Depression and Anxiety. December 06, 2016
  Background Exposure therapy, a gold‐standard treatment for anxiety disorders, is assumed to work via extinction learning, but this has never been tested. Anxious individuals demonstrate extinction learning deficits, likely related to less ventromedial prefrontal cortex (vmPFC) and more amygdala activation, but the relationship between these deficits and exposure outcome is unknown. We tested whether anxious individuals who demonstrate better extinction learning report greater anxiety reduction following brief exposure. Methods Twenty‐four adults with public speaking anxiety completed (1) functional magnetic resonance imaging during a conditioning paradigm, (2) a speech exposure session, and (3) anxiety questionnaires before and two weeks postexposure. Extinction learning was assessed by comparing ratings to a conditioned stimulus (neutral image) that was previously paired with an aversive noise against a stimulus that had never been paired. Robust regression analyses examined whether brain activation during extinction learning predicted anxiety reduction two weeks postexposure. Results On average, the conditioning paradigm resulted in acquisition and extinction effects on stimulus ratings, and the exposure session resulted in reduced anxiety two weeks post‐exposure. Consistent with our hypothesis, individuals with better extinction learning (less negative stimulus ratings), greater activation in vmPFC, and less activation in amygdala, insula, and periaqueductal gray reported greater anxiety reduction two weeks postexposure. Conclusion To our knowledge, this is the first time that the theoretical link between extinction learning and exposure outcome has been demonstrated. Future work should examine whether extinction learning can be used as a prognostic test to determine who is most likely to benefit from exposure therapy.

  December 06, 2016   doi: 10.1002/da.22583   open full text
• The moderating effects of sex on insula subdivision structure in youth with posttraumatic stress symptoms.
  Megan Klabunde, Carl F. Weems, Mira Raman, Victor G. Carrion.
  Depression and Anxiety. November 11, 2016
  Background The insula is involved in interoceptive processing, emotion awareness, and attention to salient stimuli. Research suggests that these functions are specific—albeit overlapping—within insula subdivisions. Additional studies also imply that sexual dimorphism and different rates of development occur within these subdivisions in youth. The purpose of this study was to examine potential insula subdivision structure differences in youth with PTSD symptoms as compared to controls and test sex as a moderator of these differences. Methods Insula structure (volume, surface area, and thickness) was measured with structural magnetic resonance imaging (sMRI) and calculated using Freesurfer software. We compared insula structure across age‐ and sex‐matched boys and girls with (30 with and 29 without) PTSD symptoms while also controlling for age and whole brain measurements. Results Differences were specific to the insula's anterior circular sulcus. Within this subregion, boys with PTSD symptoms demonstrated larger volume and surface area than control boys, while girls with PTSD symptoms demonstrated smaller volume and surface area than control girls. Discussion Findings indicate a potential neurobiological explanation for sex differences in youth with PTSD symptoms.

  November 11, 2016   doi: 10.1002/da.22577   open full text
• Transcranial direct current stimulation for obsessive–compulsive disorder: A randomized, controlled, partial crossover trial.
  Giordano D'Urso, Andre R. Brunoni, Maria Pia Mazzaferro, Annalisa Anastasia, Andrea Bartolomeis, Antonio Mantovani.
  Depression and Anxiety. November 01, 2016
  Background Presupplementary motor area (pre‐SMA) hyperactivity has been detected in obsessive–compulsive disorder (OCD) patients. However, it is not understood whether this is a putative primary cause or a compensatory mechanism in OCD pathophysiology. Considering the polarity‐dependent effects on cortical excitability of transcranial direct current stimulation (tDCS), we applied cathodal and/or anodal tDCS to the pre‐SMA of OCD patients to test which current polarity might better improve symptoms. Methods Twelve OCD patients received initially 10 anodal (n = 6) or cathodal (n = 6) daily consecutive 2 mA/20 min tDCS sessions with the active electrode placed bilaterally on the pre‐SMA. In case of improvement or no change in symptoms severity, the subjects were maintained on the same current polarity for 10 more sessions. In case of symptoms worsening after the first 10 sessions they were switched to the other polarity for 10 more sessions to test the hypothesis of a polarity‐dependent effect. Therefore, each subject received 20 tDCS sessions. The Yale‐Brown Obsessive–Compulsive Scale (Y‐BOCS) and the Sheehan Disability Scale (SDS) were administered biweekly to assess changes in symptoms severity. Results After 10 sessions, 50% of patients who initially received anodal stimulation were switched to cathodal, while 100% of patients initially assigned to cathodal stimulation continued on the same polarity. At the end of the study, a statistically significant decrease was observed in the mean Y‐BOCS scores of those patients who underwent cathodal tDCS. No pre–post difference was found in the scores of patients following anodal tDCS. Conclusions Cathodal but not anodal tDCS over the pre‐SMA significantly improved OCD symptoms.

  November 01, 2016   doi: 10.1002/da.22578   open full text
• What people with PTSD symptoms do (and do not) know about PTSD: A national survey.
  Juliette M. Harik, Rebecca A. Matteo, Barbara A. Hermann, Jessica L. Hamblen.
  Depression and Anxiety. October 27, 2016
  Background If people do not recognize posttraumatic stress disorder (PTSD) symptoms, they may not realize they are suffering from the disorder. Likewise, if people do not know that effective treatments exist, they may be unlikely to seek care. This study examined what people with PTSD symptoms know about PTSD and its treatment. We hypothesized that military service and prior receipt of PTSD treatment would be associated with greater PTSD knowledge. Methods We conducted an online survey assessing knowledge in three domains: trauma, PTSD symptoms, and effective PTSD treatments. Participants were 301 adults (50% veterans) who were drawn from a national research panel and screened positive for PTSD. Results When asked to identify items from a list, participants had better recognition for traumatic events (M = 72.2% of items correct) and PTSD symptoms (M = 62.3%) than for effective PTSD treatments (M = 37.9%). Across domains, participants often identified false items as true. Most participants thought divorce was a trauma that could cause PTSD, that drug addiction was a PTSD symptom, and that support groups are effective PTSD treatments. Prior receipt of PTSD treatment was associated with better symptom recognition (b = .86, P = .003). Being a military veteran was associated with better trauma recognition (b = .56, P = .025), but poorer treatment recognition (b = −.65, P = .034). Conclusions People with PTSD symptoms lack knowledge about the disorder, especially regarding effective treatments. Public education about PTSD is needed so that people recognize when to seek care and which treatments to choose.

  October 27, 2016   doi: 10.1002/da.22558   open full text
• Spared internal but impaired external reward prediction error signals in major depressive disorder during reinforcement learning.
  Jasmina Bakic, Gilles Pourtois, Marieke Jepma, Romain Duprat, Rudi Raedt, Chris Baeken.
  Depression and Anxiety. October 26, 2016
  Background Major depressive disorder (MDD) creates debilitating effects on a wide range of cognitive functions, including reinforcement learning (RL). In this study, we sought to assess whether reward processing as such, or alternatively the complex interplay between motivation and reward might potentially account for the abnormal reward‐based learning in MDD. Methods A total of 35 treatment resistant MDD patients and 44 age matched healthy controls (HCs) performed a standard probabilistic learning task. RL was titrated using behavioral, computational modeling and event‐related brain potentials (ERPs) data. Results MDD patients showed comparable learning rate compared to HCs. However, they showed decreased lose‐shift responses as well as blunted subjective evaluations of the reinforcers used during the task, relative to HCs. Moreover, MDD patients showed normal internal (at the level of error‐related negativity, ERN) but abnormal external (at the level of feedback‐related negativity, FRN) reward prediction error (RPE) signals during RL, selectively when additional efforts had to be made to establish learning. Conclusions Collectively, these results lend support to the assumption that MDD does not impair reward processing per se during RL. Instead, it seems to alter the processing of the emotional value of (external) reinforcers during RL, when additional intrinsic motivational processes have to be engaged.

  October 26, 2016   doi: 10.1002/da.22576   open full text
• A simple attention test in the acute phase of a major depressive episode is predictive of later functional remission.
  Marie‐Laure Cléry‐Melin, Philip Gorwood.
  Depression and Anxiety. October 26, 2016
  Background Functional recovery after a major depressive episode (MDE) requires both clinical remission and preservation of cognitive skills. As attentional deficit may persist after remission, leading to functional impairment, its role as a prognosis marker needs to be considered. Methods Five hundred eight depressed outpatients (DSM‐IV) were assessed at baseline for clinical symptoms (QIDS‐SR), social functioning (Sheehan Disability Scale, SDS) and attention through the d2 test of attention and the trail making test, simple tests, respectively, requiring to quote or to interconnect relevant items. All patients were treated by agomelatine, and examined 6 to 8 weeks after baseline to assess clinical remission (QIDS‐SR ≤ 5) and/or functional remission (SDS ≤ 6). Results At follow up, 154 patients (31%) were in clinical and functional remission. Shorter cumulative duration of prior depression, shorter present MDE, and two parameters of the d2 test of attention were predictive of such positive outcome, the number of omission mistakes (F1) being the only one still significantly predictive (P < .05) with a multivariate approach. F1 was unchanged after remission, patients with less than 11 mistakes had a 2.27 times increased chance to reach full remission, and a dose–response relationship was observed, with a regular increase of positive outcome for less mistakes. Conclusions The number of omission mistakes (F1) of the d2 test of attention was a stable marker, being predictive of, and with a dose‐effect for, clinical plus functional remission. It may constitute a specific marker of attentional deficit, involved in the resilience process that enables individuals to develop more adequate strategies to cope with everyday functional activities.

  October 26, 2016   doi: 10.1002/da.22575   open full text
• Improving outcomes for patients with medication‐resistant anxiety: effects of collaborative care with cognitive behavioral therapy.
  Laura Campbell‐Sills, Peter P. Roy‐Byrne, Michelle G. Craske, Alexander Bystritsky, Greer Sullivan, Murray B. Stein.
  Depression and Anxiety. October 24, 2016
  Background Many patients with anxiety disorders remain symptomatic after receiving evidence‐based treatment, yet research on treatment‐resistant anxiety is limited. We evaluated effects of cognitive behavioral therapy (CBT) on outcomes of patients with medication‐resistant anxiety disorders using data from the Coordinated Anxiety Learning and Management (CALM) trial. Methods Primary care patients who met study entry criteria (including DSM‐IV diagnosis of generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or social anxiety disorder) despite ongoing pharmacotherapy of appropriate type, dose, and duration were classified as medication resistant (n = 227). Logistic regression was used to estimate effects of CALM's CBT program (CALM‐CBT; chosen by 104 of 117 medication‐resistant patients randomized to CALM) versus usual care (UC; n = 110) on response [≥ 50% reduction of 12‐item Brief Symptom Inventory (BSI‐12) anxiety and somatic symptom score] and remission (BSI‐12 < 6) at 6, 12, and 18 months. Within‐group analyses examined outcomes by treatment choice (CBT vs. CBT plus medication management) and CBT dose. Results Approximately 58% of medication‐resistant CALM‐CBT patients responded and 46% remitted during the study. Relative to UC, CALM‐CBT was associated with greater response at 6 months (AOR = 3.78, 95% CI 2.02‐7.07) and 12 months (AOR = 2.49, 95% CI 1.36‐4.58) and remission at 6, 12, and 18 months (AORs = 2.44 to 3.18). Patients in CBT plus medication management fared no better than those in CBT only. Some evidence suggested higher CBT dose produced better outcomes. Conclusions CBT can improve outcomes for patients whose anxiety symptoms are resistant to standard pharmacotherapy.

  October 24, 2016   doi: 10.1002/da.22574   open full text
• Cross‐national epidemiology of panic disorder and panic attacks in the world mental health surveys.
  Peter Jonge, Annelieke M. Roest, Carmen C.W. Lim, Silvia E. Florescu, Evelyn J. Bromet, Dan J. Stein, Meredith Harris, Vladimir Nakov, Jose Miguel Caldas‐de‐Almeida, Daphna Levinson, Ali O. Al‐Hamzawi, Josep Maria Haro, Maria Carmen Viana, Guilherme Borges, Siobhan O'Neill, Giovanni Girolamo, Koen Demyttenaere, Oye Gureje, Noboru Iwata, Sing Lee, Chiyi Hu, Aimee Karam, Jacek Moskalewicz, Viviane Kovess‐Masfety, Fernando Navarro‐Mateu, Mark Oakley Browne, Marina Piazza, José Posada‐Villa, Yolanda Torres, Margreet L. ten Have, Ronald C. Kessler, Kate M. Scott.
  Depression and Anxiety. October 24, 2016
  Context The scarcity of cross‐national reports and the changes in Diagnostic and Statistical Manual version 5 (DSM‐5) regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population. Objective To present representative data about the cross‐national epidemiology of PD and PAs in accordance with DSM‐5 definitions. Design and setting Nationally representative cross‐sectional surveys using the World Health Organization Composite International Diagnostic Interview version 3.0. Participants Respondents (n = 142,949) from 25 high, middle, and lower‐middle income countries across the world aged 18 years or older. Main outcome measures PD and presence of single and recurrent PAs. Results Lifetime prevalence of PAs was 13.2% (SE 0.1%). Among persons that ever had a PA, the majority had recurrent PAs (66.5%; SE 0.5%), while only 12.8% fulfilled DSM‐5 criteria for PD. Recurrent PAs were associated with a subsequent onset of a variety of mental disorders (OR 2.0; 95% CI 1.8–2.2) and their course (OR 1.3; 95% CI 1.2–2.4) whereas single PAs were not (OR 1.1; 95% CI 0.9–1.3 and OR 0.7; 95% CI 0.6–0.8). Cross‐national lifetime prevalence estimates were 1.7% (SE 0.0%) for PD with a median age of onset of 32 (IQR 20–47). Some 80.4% of persons with lifetime PD had a lifetime comorbid mental disorder. Conclusions We extended previous epidemiological data to a cross‐national context. The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology.

  October 24, 2016   doi: 10.1002/da.22572   open full text
• Prediction of suicidal behavior in high risk psychiatric patients using an assessment of acute suicidal state: The suicide crisis inventory.
  Igor Galynker, Zimri S. Yaseen, Abigail Cohen, Ori Benhamou, Mariah Hawes, Jessica Briggs.
  Depression and Anxiety. October 06, 2016
  Background We have developed the Suicide Crisis Inventory (SCI) to evaluate the intensity of the Suicidal Crisis Syndrome, an acute state hypothesized to precede suicide attempt. The psychometric properties of the SCI, including predictive validity for suicidal behavior (SB), were assessed. Methods Adult psychiatric patients (n = 201) hospitalized for high suicide risk were assessed. Logistic regression models assessed the SCI's predictive validity for SB in the 4–8 weeks following hospital discharge and its incremental predictive validity over traditional risk factors (n = 137, 64% f/u rate). Internal structure, reliability, convergent and discriminant validity, and state versus trait properties were also assessed. Results The SCI had excellent internal consistency (Cronbach's α 0.970). The SCI total score at discharge predicted short‐term SB with 64% sensitivity 88% specificity (OR = 13, P = .003) at its optimal cut score. In a test of its incremental predictive validity, SCI total score at discharge improved prediction of SB over traditional risk factors (Chi‐squared 5.597, P = .024, model P = .001), with AOR 2.02 (P = .030). The SCI admission versus discharge test–retest reliability and score distributions showed it to be an acute state measure. Conclusion The SCI was predictive of future SB in high‐risk psychiatric inpatients during the crucial weeks following their hospital discharge. Further validation in diverse patient populations is needed.

  October 06, 2016   doi: 10.1002/da.22559   open full text
• Six‐year trajectory of objective physical function in persons with depressive and anxiety disorders.
  Bianca A. Lever‐van Milligen, Femke Lamers, Jan H. Smit, Brenda W. J. H. Penninx.
  Depression and Anxiety. October 04, 2016
  Background Depression and anxiety have been related to poorer self‐reported physical functioning over time; however, objective measures of physical function are less frequently examined. This study assessed the 6‐year trajectory of hand‐grip strength and lung function in persons with depressive and/or anxiety disorders. Methods At four waves (baseline, 2, 4, and 6 years) hand‐grip strength and lung function were assessed in 2,480 participants, aged 18–65 years, of the Netherlands Study of Depression and Anxiety. Linear mixed models were used to examine the association between baseline psychiatric status (current and remitted depression and anxiety, healthy controls) and physical function during 6‐year follow‐up, adjusted for sociodemographics, lifestyle, and health indicators. Results Although there were no differences in the rate of decline over time, women with current, but not remitted, depression and anxiety had poorer hand‐grip strength (B = −1.34, P < .001) and poorer lung function (B = −11.91, P =.002) compared to healthy women during the entire 6‐year follow‐up. Associations with depression and anxiety severity measures confirmed dose–response relationships with objective physical function. In men, stronger 6‐year decline of lung function was found in those with current disorders (current diagnosis‐by‐time: B = −11.72, P = .002) and even in those with remitted disorders (remitted diagnosis by time: B = −10.11, P = .04) compared to healthy men. Conclusions Depression and anxiety are associated with consistently poorer hand‐grip strength in women and poorer lung function in women and men over 6 years of time, implicating their long‐lasting impact on physical functioning.

  October 04, 2016   doi: 10.1002/da.22557   open full text
• Treatment and Prevention of Depression and Anxiety in Youth: Test of Cross‐Over Effects.
  Judy Garber, Steven M. Brunwasser, Argero A. Zerr, Karen T.G. Schwartz, Karen Sova, V. Robin Weersing.
  Depression and Anxiety. October 03, 2016
  Anxiety and depression are highly comorbid and share several common etiological processes. Therefore, it may be more efficient to develop interventions that treat or prevent these problems together rather than as separate entities. The present meta‐analytic review examined whether interventions for children and adolescents that explicitly targeted either anxiety or depression showed treatment specificity or also impacted the other outcome (i.e. cross‐over effects). We addressed this question both within the same type of study (i.e. treatment, prevention) and across study types. Only randomized controlled trials (RCTs) that assessed both constructs with dimensional measures were included in this review. For treatment studies, RCTs targeting anxiety (n = 18) showed significant effects on both anxious and depressive symptoms, although more strongly on anxiety than depression; similarly, RCTs treating depression (n = 9) yielded significant effects on both depressive and anxious symptoms, but stronger effects on depression than anxiety. Thus, there were cross‐over effects in treatments purportedly targeting either anxiety or depression, and also treatment specificity, such that larger effects were seen for the target problem at which the treatment was aimed. Anxiety prevention studies (n = 14) significantly affected anxious, but not depressive symptoms, indicating no cross‐over effect of anxiety prevention trials on depression. For depression prevention studies (n = 15), the effects were not significant for either depressive or anxiety symptoms, although the effect was significantly larger for depressive than for anxious symptoms. Post‐hoc analyses revealed that the effect on depressive symptoms was significant in depression preventions trials of targeted but not universal samples. Implications for transdiagnostic interventions are discussed.

  October 03, 2016   doi: 10.1002/da.22519   open full text
• Treatment for Anhedonia: A Neuroscience Driven Approach.
  Michelle G. Craske, Alicia E. Meuret, Thomas Ritz, Michael Treanor, Halina J. Dour.
  Depression and Anxiety. October 03, 2016
  Anhedonia, or loss of interest or pleasure in usual activities, is characteristic of depression, some types of anxiety, as well as substance abuse and schizophrenia. Anhedonia is a predictor of poor long‐term outcomes, including suicide, and poor treatment response. Because extant psychological and pharmacological treatments are relatively ineffective for anhedonia, there is an unmet therapeutic need for this high‐risk symptom. Current psychological and drug treatments for anxiety and depression focus largely on reducing excesses in negative affect rather than improving deficits in positive affect. Recent advances in affective neuroscience posit that anhedonia is associated with deficits in the appetitive reward system, specifically the anticipation, consumption, and learning of reward. In this paper, we review the evidence for positive affect as a symptom cluster, and its neural underpinnings, and introduce a novel psychological treatment for anxiety and depression that targets appetitive responding. First, we review anhedonia in relation to positive and negative valence systems and current treatment approaches. Second, we discuss the evidence linking anhedonia to biological, experiential, and behavioral deficits in the reward subsystems. Third, we describe the therapeutic approach for Positive Affect Treatment (PAT), an intervention designed to specifically target deficits in reward sensitivity.

  October 03, 2016   doi: 10.1002/da.22490   open full text
• Amygdala–Cortical Connectivity: Associations with Anxiety, Development, and Threat.
  Andrea L. Gold, Tomer Shechner, Madeline J. Farber, Carolyn N. Spiro, Ellen Leibenluft, Daniel S. Pine, Jennifer C. Britton.
  Depression and Anxiety. October 03, 2016
  Background Amygdala–prefrontal cortex (PFC) functional connectivity may be influenced by anxiety and development. A prior study on anxiety found age‐specific dysfunction in the ventromedial PFC (vmPFC), but not amygdala, associated with threat‐safety discrimination during extinction recall (Britton et al.). However, translational research suggests that amygdala–PFC circuitry mediates responses following learned extinction. Anxiety‐related perturbations may emerge in functional connectivity within this circuit during extinction recall tasks. The current report uses data from the prior study to examine how anxiety and development relate to task‐dependent amygdala–PFC connectivity. Methods Eighty‐two subjects (14 anxious youths, 15 anxious adults, 25 healthy youths, 28 healthy adults) completed an extinction recall task, which directed attention to different aspects of stimuli. Generalized psychophysiological interaction analysis tested whether task‐dependent functional connectivity with anatomically defined amygdala seed regions differed across anxiety and age groups. Results Whole‐brain analyses showed significant interactions of anxiety, age, and attention task (i.e., threat appraisal, explicit threat memory, physical discrimination) on left amygdala functional connectivity with the vmPFC and ventral anterior cingulate cortex (Talairach XYZ coordinates: −16, 31, −6 and 1, 36, −4). During threat appraisal and explicit threat memory (vs. physical discrimination), anxious youth showed more negative amygdala–PFC coupling, whereas anxious adults showed more positive coupling. Conclusions In the context of extinction recall, anxious youths and adults manifested opposite directions of amygdala–vmPFC coupling, specifically when appraising and explicitly remembering previously learned threat. Future research on anxiety should consider associations of both development and attention to threat with functional connectivity perturbations.

  October 03, 2016   doi: 10.1002/da.22470   open full text
• The Role of BDNF in the Development of Fear Learning.
  Iva Dincheva, Niccola B. Lynch, Francis S. Lee.
  Depression and Anxiety. October 03, 2016
  Brain‐derived neurotrophic factor (BDNF) is a growth factor that is dynamically expressed in the brain across postnatal development, regulating neuronal differentiation and synaptic plasticity. The neurotrophic hypothesis of psychiatric mood disorders postulates that in the adult brain, decreased BDNF levels leads to altered neural plasticity, contributing to disease. Although BDNF has been established as a key factor regulating the critical period plasticity in the developing visual system, it has recently been shown to also play a role in fear circuitry maturation, which has implications for the emergence of fear‐related mood disorders. This review provides a detailed overview of developmental changes in expression of BDNF isoforms, as well as their receptors across postnatal life. In addition, recent developmental studies utilizing a genetic BDNF single nucleotide polymorphism (Val66Met) knock‐in mouse highlight the impact of BDNF on fear learning during a sensitive period spanning the transition into adolescent time frame. We hypothesize that BDNF in the developing brain regulates fear circuit plasticity during a sensitive period in early adolescence, and alterations in BDNF expression (genetic or environmental) have a persistent impact on fear behavior and fear‐related disorders.

  October 03, 2016   doi: 10.1002/da.22497   open full text
• Kappa‐Opioid Antagonists for Psychiatric Disorders: From Bench to Clinical Trials.
  William A. Carlezon, Andrew D. Krystal.
  Depression and Anxiety. October 03, 2016
  Kappa‐opioid receptor (KOR) antagonists are currently being considered for the treatment of a variety of neuropsychiatric conditions, including depressive, anxiety, and substance abuse disorders. A general ability to mitigate the effects of stress, which can trigger or exacerbate these conditions, may explain their putative efficacy across such a broad array of conditions. The discovery of their potentially therapeutic effects evolved from preclinical research designed to characterize the molecular mechanisms by which experience causes neuroadaptations in the nucleus accumbens (NAc), a key element of brain reward circuitry. This research established that exposure to drugs of abuse or stress increases the activity of the transcription factor CREB (cAMP response element binding protein) in the NAc, which leads to elevated expression of the opioid peptide dynorphin that in turn causes core signs of depressive‐ and anxiety‐related disorders. Disruption of KORs—the endogenous receptors for dynorphin—produces antidepressant‐ and anxiolytic‐like actions in screening procedures that identify standard drugs of these classes, and reduces stress effects in tests used to study addiction and stress‐related disorders. Although interest in this target is high, prototypical KOR antagonists have extraordinarily persistent pharmacodynamic effects that complicate clinical trials. The development of shorter acting KOR antagonists together with more rapid designs for clinical trials may soon provide insight on whether these drugs are efficacious as would be predicted by preclinical work. If successful, KOR antagonists would represent a unique example in psychiatry where the therapeutic mechanism of a drug class is understood before it is shown to be efficacious in humans.

  October 03, 2016   doi: 10.1002/da.22500   open full text
• Psychobiology of the intersection and divergence of depression and anxiety.
  Diego A. Pizzagalli.
  Depression and Anxiety. October 03, 2016
  There is no abstract available for this paper.

  October 03, 2016   doi: 10.1002/da.22550   open full text
• Self‐reported obstructive sleep apnea is associated with nonresponse to antidepressant pharmacotherapy in late‐life depression.
  Lauren Waterman, Sarah T. Stahl, Daniel J. Buysse, Eric J. Lenze, Daniel Blumberger, Benoit Mulsant, Meryl Butters, Marie Anne Gebara, Charles F. Reynolds, Jordan F. Karp.
  Depression and Anxiety. September 16, 2016
  Background Obstructive sleep apnea (OSA) is frequently comorbid with late‐life depression. The purpose of this project was to determine, using a sample of older adults with major depressive disorder, whether patient‐reported diagnosis of OSA was associated with rate of response to venlafaxine. Methods Participants from this multisite study were adults ≥60 years old (n = 468) with major depressive disorder and a Montgomery Asberg Depression Rating Scale (MADRS) score of ≥15. Depression response was the outcome variable, defined as a MADRS score of ≤10 for two consecutive assessments at the end of 12 weeks of open‐label treatment with venlafaxine 300 mg/day. To assess OSA, participants were asked if they had been diagnosed with OSA using polysomnography. Results Eighty participants (17.1%) reported a diagnosis of OSA prior to baseline. Participants with OSA were more likely to be male, report greater impairment on measures of health, experience a longer duration of the index episode, and receive an adequate antidepressant trial prior to entering the study. During the 12 weeks of treatment, 40.8% responded to treatment with venlafaxine (43.6%, n = 169/388 of the no OSA group, and 27.5%, n = 22/80 of the OSA group). Participants without OSA were 1.79 times more likely to respond to treatment (HR: 1.79 [95%CI: 1.13–2.86], P < .05) compared to those with OSA. Conclusions OSA may impair response to antidepressant pharmacotherapy in depressed older adults. Future studies of antidepressant response rates among depressed older adults with OSA should both prospectively diagnose OSA and monitor adherence to treatments such as continuous positive airway pressure.

  September 16, 2016   doi: 10.1002/da.22555   open full text
• Effectiveness of a culturally attuned Internet‐based depression prevention program for Chinese adolescents: A randomized controlled trial.
  Patrick Ip, David Chim, Ko Ling Chan, Tim M.H. Li, Frederick Ka Wing Ho, Benjamin W. Voorhees, Agnes Tiwari, Anita Tsang, Charlie Wai Leung Chan, Matthew Ho, Winnie Tso, Wilfred Hing Sang Wong.
  Depression and Anxiety. September 13, 2016
  Background Depression prevention among adolescents is crucial for reducing the global disease burden. Internet‐based depression prevention approaches are found to be effective but they were mostly evaluated in a Western context. Grasping the Opportunity is a Chinese Internet intervention, which was translated and modified from CATCH‐IT developed in the West. We aimed to evaluate the effectiveness of Grasp the Opportunity in reducing depressive symptoms in Chinese adolescents. Methods In this randomized controlled trial, Chinese adolescents aged 13 to 17 years with mild‐to‐moderate depressive symptoms were recruited from three secondary schools in Hong Kong. The participants (n = 257) were randomly assigned to receive either intervention or attention control. The primary outcome was the improvement in depressive symptoms according to the revised Center for Epidemiologic Studies Depression Scale (CESD‐R) at the 12‐month follow‐up. Analyses were performed using intention to treat (ITT). Results The participants were randomly assigned to receive the intervention (n = 130) or attention control (n = 127). Follow‐up data were obtained from 250 (97%) participants. Only 26 (10%) participants completed the intervention. Compared to the attention control, Grasp the Opportunity led to reductions in depressive symptoms at the 12‐month follow‐up with a medium effect size using ITT analysis (mean difference 2.6, 95% CI 0.59–5.55, effect size d = 0.36). Conclusions Grasp the Opportunity is effective in reducing depressive symptoms in Chinese adolescents over a long follow‐up period. Poor completion rate is the major challenge in the study.

  September 13, 2016   doi: 10.1002/da.22554   open full text
• Persistent maternal depressive symptoms trajectories influence children's IQ: The EDEN mother–child cohort.
  Judith der Waerden, Jonathan Y. Bernard, Maria Agostini, Marie‐Josèphe Saurel‐Cubizolles, Hugo Peyre, Barbara Heude, Maria Melchior,.
  Depression and Anxiety. September 07, 2016
  Background This study assessed the association between timing and course of maternal depression from pregnancy onwards and children's cognitive development at ages 5 to 6. Potential interaction effects with child sex and family socioeconomic status were explored. Methods One thousand thirty‐nine mother–child pairs from the French EDEN mother–child birth cohort were followed from 24 to 28 weeks of pregnancy onwards. Based on Center for Epidemiological Studies Depression (CES‐D) and Edinburgh Postnatal Depression Scale (EPDS) scores assessed at six timepoints, longitudinal maternal depressive symptom trajectories were calculated with a group‐based semiparametric method. Children's cognitive function was assessed at ages 5 to 6 by trained interviewers with the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI‐III), resulting in three composite scores: Verbal IQ (VIQ), Performance IQ (PIQ), and Full‐Scale IQ (FSIQ). Results Five trajectories of maternal symptoms of depression could be distinguished: no symptoms, persistent intermediate‐level depressive symptoms, persistent high depressive symptoms, high symptoms in pregnancy only, and high symptoms in the child's preschool period only. Multiple linear regression analyses showed that, compared to children of mothers who were never depressed, children of mothers with persistent high levels of depressive symptoms had reduced VIQ, PIQ, and FSIQ scores. This association was moderated by the child's sex, boys appearing especially vulnerable in case of persistent maternal depression. Conclusions Chronicity of maternal depression predicts children's cognitive development at school entry age, particularly in boys. As maternal mental health is an early modifiable influence on child development, addressing the treatment needs of depressed mothers may help reduce the associated burden on the next generation.

  September 07, 2016   doi: 10.1002/da.22552   open full text
• Latent class analysis of the feared situations of social anxiety disorder: A population‐based study.
  Hugo Peyre, Nicolas Hoertel, Fabrice Rivollier, Benjamin Landman, Kibby McMahon, Astrid Chevance, Cédric Lemogne, Richard Delorme, Carlos Blanco, Frédéric Limosin.
  Depression and Anxiety. August 30, 2016
  Background Little is known about differences in mental health comorbidity and quality of life in individuals with social anxiety disorder (SAD) according to the number and the types of feared situations. Methods Using a US nationally representative sample, the National Epidemiologic Survey on Alcohol and Related Conditions, we performed latent class analysis to compare the prevalence rates of mental disorders and quality of life measures across classes defined by the number and the types of feared social situations among individuals with SAD. Results Among the 2,448 participants with a lifetime diagnosis of SAD, we identified three classes of individuals who feared most social situations but differed in the number of feared social situations (generalized severe [N = 378], generalized moderate [N = 1,049] and generalized low [N = 443]) and a class of subjects who feared only performance situations [N = 578]. The magnitude of associations between each class and a wide range of mental disorders and quality of life measures were consistent with a continuum model, supporting that the deleterious effects of SAD on mental health may increase with the number of social situations feared. However, we found that individuals with the “performance only” specifier may constitute an exception to this model because these participants had significantly better mental health than other participants with SAD. Conclusions Our findings give additional support to the recent changes made in the DSM‐5, including the introduction of the “performance only” specifier and the removal of the “generalized” specifier to promote the dimensional approach of the number of social fears.

  August 30, 2016   doi: 10.1002/da.22547   open full text
• Effect of as‐needed use of intranasal PH94B on social and performance anxiety in individuals with social anxiety disorder.
  Michael R. Liebowitz, Rita Hanover, Ann Draine, Rita Lemming, Jason Careri, Louis Monti.
  Depression and Anxiety. August 25, 2016
  Background There are no medications approved for as‐needed use for feared situations for individuals with social anxiety disorder (SAD). In the present study, intranasal PH94B was provided for use as needed during stressful events. Methods Twenty‐two subjects were randomized (double‐blind) to 2 weeks of treatment with intranasal PH94B or placebo. Following self‐administration of medication prior to a feared event, peak levels of anxiety were recorded using the Subjective Units of Distress Scale (SUDS). After 2 weeks, subjects were crossed over to the opposite treatment for 2 weeks. Average peak SUDS during treatment with PH94B and placebo were compared using a paired t‐test. Results Significant differences in favor of PH94B were found on the primary outcome measure: mean peak SUDS change from baseline for all subjects receiving PH94B was 15.6 points versus 8.3 points for placebo (paired t = 3.09, P = .006, effect size of .658). PH94B showed less superiority over placebo when placebo was given second rather than first, likely due to a carryover effect. Looking between groups at just the first 2 weeks of treatment, PH94B also showed trend superiority to placebo on the Liebowitz Social Anxiety Scale (LSAS) (P = .07) and a significant difference on the Patient Global Impression of Change (P = .024) and the LSAS Avoidance subtotal (P = .02). Conclusions While further study is needed, these results, combined with earlier findings, suggest that PH94B could represent a useful as‐needed treatment for SAD, and continue to validate the nasal chemosensory system as a novel mechanism for medication delivery.

  August 25, 2016   doi: 10.1002/da.22546   open full text
• Individual differences in cognitive reappraisal use and emotion regulatory brain function in combat‐exposed veterans with and without PTSD.
  Jacklynn M. Fitzgerald, Annmarie MacNamara, Amy E. Kennedy, Christine A. Rabinak, Sheila A.M. Rauch, Israel Liberzon, K. Luan Phan.
  Depression and Anxiety. August 25, 2016
  Background Veterans with posttraumatic stress disorder (PTSD) exhibit marked deficits in emotion regulation. Past research has demonstrated underengagement of the prefrontal cortex during regulation of negative affect in those with PTSD, but has been unable to find evidence of impaired downregulation of the amygdala. One possibility is that there exists variability in amygdala reactivity that cuts across diagnostic status and which can be characterized using a continuous measure of individual differences. In healthy/nontraumatized volunteers, individual variability in amygdala engagement during emotion processing and regulation has been shown to relate to habitual use of regulation strategies. Methods The current study examined whether self‐reported use of cognitive reappraisal and expressive suppression regulation strategies correlated with brain activation during cognitive reappraisal in combat‐exposed veterans with (n = 28) and without PTSD (combat‐exposed controls, CEC; n = 20). Results Results showed that greater self‐reported use of cognitive reappraisal was associated with less activation in the right amygdala during volitional attempts to attenuate negative affect using reappraisal, irrespective of PTSD diagnosis. Conclusions This finding is in line with prior work and extends evidence of an association between habitual use of regulation strategies and amygdala engagement during emotion regulation to a trauma‐exposed sample of individuals both with and without PTSD. Furthermore, by providing evidence of individual differences in regulation‐related amygdala response in a traumatized sample, this result may increase understanding of the neural mechanisms that support variability in symptom manifestation observed across individuals with PTSD.

  August 25, 2016   doi: 10.1002/da.22551   open full text
• Decrease in somatostatin‐positive cell density in the amygdala of females with major depression.
  Gaelle Douillard‐Guilloux, David Lewis, Marianne L. Seney, Etienne Sibille.
  Depression and Anxiety. August 24, 2016
  Background Somatostatin (SST) is a neuropeptide expressed in a subtype of gamma‐aminobutyric acid (GABA) interneurons that target the dendrites of pyramidal neurons. We previously reported reduced levels of SST gene and protein expression in the postmortem amygdala of subjects with major depressive disorder (MDD). This reduction was specific to female subjects with MDD. Methods Here, we used in situ hybridization to examine the regional and cellular patterns of reductions in SST expression in a cohort of female MDD subjects with known SST deficits in the amygdala (N = 10/group). Results We report a significant reduction in the density of SST‐labeled neurons in the lateral, basolateral, and basomedial nuclei of the amygdala of MDD subjects compared to controls. SST mRNA levels per neuron did not differ between MDD and control subjects in the lateral or basolateral nuclei, but were lower in the basomedial nucleus. There was no difference in cross‐sectional density of total cells. Conclusions In summary, we report an MDD‐related reduction in the density of detectable SST‐positive neurons across several nuclei in the amygdala, with a reduction in SST mRNA per cell restricted to the basomedial nucleus. In the absence of changes in total cell density, these results suggest the possibility of a change in SST cell phenotype rather than cell death in the amygdala of female MDD subjects.

  August 24, 2016   doi: 10.1002/da.22549   open full text
• Catastrophizing, rumination, and reappraisal prospectively predict adolescent PTSD symptom onset following a terrorist attack.
  Jessica L. Jenness, Shari Jager‐Hyman, Charlotte Heleniak, Aaron T. Beck, Margaret A. Sheridan, Katie A. McLaughlin.
  Depression and Anxiety. August 24, 2016
  Background Disruptions in emotion regulation are a transdiagnostic risk factor for psychopathology. However, scant research has examined whether emotion regulation strategies are related to the onset of posttraumatic stress disorder (PTSD) symptoms among youths exposed to trauma. We investigated whether pretrauma emotion regulation strategies prospectively predicted PTSD symptom onset after the 2013 Boston Marathon terrorist attack among adolescents and whether these associations were moderated by the degree of exposure to media coverage of the attack. Methods A sample of 78 Boston‐area adolescents (mean age = 16.72 years, 65% female) who previously participated in studies assessing emotion regulation and psychopathology were recruited following the terrorist attack. Within 4 weeks of the attack, we assessed self‐reported PTSD symptoms and attack‐related media exposure via an online survey. We examined the association of pretrauma emotion regulation strategies with PTSD symptom onset after adjustment for pretrauma internalizing symptoms and violence exposure. Results Greater pretrauma engagement in rumination predicted onset of PTSD symptoms following the attack. Adolescents who engaged in catastrophizing also had greater PTSD symptoms postattack, but only when exposed to high levels of media coverage of the attacks; the same pattern was observed for adolescents who engaged in low levels of cognitive reappraisal. Conclusions Engagement in specific emotion regulation strategies prior to a traumatic event predicts the onset of PTSD symptoms among youths exposed to trauma, extending transdiagnostic models of emotion regulation to encompass trauma‐related psychopathology in children and adolescents.

  August 24, 2016   doi: 10.1002/da.22548   open full text
• Comorbid anxiety increases cognitive control activation in Major Depressive Disorder.
  Natania A. Crane, Lisanne M. Jenkins, Catherine Dion, Kortni K. Meyers, Anne L. Weldon, Laura B. Gabriel, Sara J. Walker, David T. Hsu, Douglas C. Noll, Heide Klumpp, K. Luan Phan, Jon‐Kar Zubieta, Scott A. Langenecker.
  Depression and Anxiety. July 25, 2016
  Background Major Depressive Disorder (MDD) and anxiety disorders often co‐occur, with poorer treatment response and long‐term outcomes. However, little is known about the shared and distinct neural mechanisms of comorbid MDD and anxiety (MDD+Anx). This study examined how MDD and MDD+Anx differentially impact cognitive control. Methods Eighteen MDD, 29 MDD+Anx, and 54 healthy controls (HC) completed the Parametric Go/No‐Go (PGNG) during fMRI, including Target, Commission, and Rejection trials. Results MDD+Anx had more activation in the anterior dorsolateral prefrontal cortex, hippocampus, and caudate during Rejections, and inferior parietal lobule during correct Targets than MDD and HC. During Rejections HC had greater activation in a number of cognitive control regions compared to MDD; in the posterior cingulate compared to MDD+Anx; and in the fusiform gyrus compared to all MDD. During Commissions HC had greater activation in the right inferior frontal gyrus than all MDD. MDD had more activation in the mid‐cingulate, inferior parietal lobule, and superior temporal gyrus than MDD+Anx during Commissions. Conclusions Despite similar performance, MDD and MDD+Anx showed distinct differences in neural mechanisms of cognitive control in relation to each other, as well as some shared differences in relation to HC. The results were consistent with our hypothesis of hypervigilance in MDD+Anx within the cognitive control network, but inconsistent with our hypothesis that there would be greater engagement of salience and emotion network regions. Comorbidity of depression and anxiety may cause increased heterogeneity in study samples, requiring further specificity in detection and measurement of intermediate phenotypes and treatment Targets.

  July 25, 2016   doi: 10.1002/da.22541   open full text
• Disqualified qualifiers: evaluating the utility of the revised DSM‐5 definition of potentially traumatic events among area youth following the Boston marathon bombing.
  Tommy Chou, Aubrey L. Carpenter, Caroline E. Kerns, R. Meredith Elkins, Jennifer Greif Green, Jonathan S. Comer.
  Depression and Anxiety. July 19, 2016
  Background The DSM‐5 includes a revised definition of the experiences that qualify as potentially traumatic events. This revised definition now offers a clearer and more exclusive definition of what qualifies as a traumatic exposure, but little is known about the revision's applicability to youth populations. The present study evaluated the predictive utility of the revised DSM definitional boundaries of traumatic exposure in a sample of youth exposed to the 2013 Boston Marathon bombing and related events Methods Caregivers (N = 460) completed surveys 2 to 6 months postbombing about youth experiences during the events and youth posttraumatic stress (PTS) symptoms Results Experiencing DSM‐5 qualifying traumatic events (DSM‐5 QTEs) significantly predicted child PTS symptoms (PTSS), whereas DSM‐5 nonqualifying stressful experiences (DSM‐5 non‐QSEs) did not after accounting for DSM‐5 QTEs. Importantly, child age moderated the relationship between DSM‐5 QTEs and PTSS such that children 7 and older who experienced DSM‐5 QTEs showed greater postbombing PTSS, whereas there was no such relationship in children ages 6 and below Conclusions Data largely support the revised posttraumatic stress disorder (PTSD) definition of QTEs in older youth, and also highlight the need for further refinement of the QTE definition for children ages 6 and below.

  July 19, 2016   doi: 10.1002/da.22543   open full text
• Pathways to anxiety–depression comorbidity: A longitudinal examination of childhood anxiety disorders.
  Courtney Benjamin Wolk, Matthew M. Carper, Philip C. Kendall, Thomas M. Olino, Steven C. Marcus, Rinad S. Beidas.
  Depression and Anxiety. July 19, 2016
  Background Anxiety disorders are prevalent in youth and associated with later depressive disorders. A recent model posits three distinct anxiety–depression pathways. Pathway 1 represents youth with a diathesis to anxiety that increases risk for depressive disorders; Pathway 2 describes youth with a shared anxiety‐depression diathesis; and Pathway 3 consists of youth with a diathesis for depression who develop anxiety as a consequence of depression impairment. This is the first partial test of this model following cognitive‐behavioral treatment (CBT) for child anxiety. Method The present study included individuals (N = 66; M age = 27.23 years, SD = 3.54) treated with CBT for childhood anxiety disorders 7–19 years (M = 16.24; SD = 3.56) earlier. Information regarding anxiety (i.e., social phobia (SoP), separation anxiety disorder (SAD), generalized anxiety disorder (GAD)) and mood disorders (i.e., major depressive disorder (MDD) and dysthymic disorders) was obtained at pretreatment, posttreatment, and one or more follow‐up intervals via interviews and self‐reports. Results Evidence of pathways from SoP, SAD, and GAD to later depressive disorders was not observed. Treatment responders evidenced reduced GAD and SoP over time, although SoP was observed to have a more chronic and enduring pattern. Conclusions Evidence for typically observed pathways from childhood anxiety disorders was not observed. Future research should prospectively examine if CBT treatment response disrupts commonly observed pathways.

  July 19, 2016   doi: 10.1002/da.22544   open full text
• Long‐term cost‐effectiveness of cognitive behavioral therapy versus psychodynamic therapy in social anxiety disorder.
  Nina Egger, Alexander Konnopka, Manfred E. Beutel, Stephan Herpertz, Wolfgang Hiller, Juergen Hoyer, Simone Salzer, Ulrich Stangier, Bernhard Strauss, Ulrike Willutzki, Joerg Wiltink, Eric Leibing, Falk Leichsenring, Hans‐Helmut König.
  Depression and Anxiety. July 18, 2016
  Background To determine the cost‐effectiveness of cognitive behavioral therapy (CBT) versus psychodynamic therapy (PDT) in the treatment of social anxiety disorder after a follow‐up of 30 months from a societal perspective. Methods This analysis was conducted alongside the multicenter SOPHO‐NET trial; adults with a primary diagnosis of social anxiety disorder received CBT (n = 209) or PDT (n = 207). Data on health care utilization and productivity loss were collected at baseline, after 6 months (posttreatment), and three further follow‐ups to calculate direct and indirect costs. Anxiety‐free days (AFDs) calculated based on remission and response were used as measure of effect. The incremental cost‐effectiveness ratio (ICER) was determined. Net benefit regressions, adjusted for comorbidities and baseline differences, were applied to derive cost‐effectiveness acceptability curves. Results In the descriptive analysis, the unadjusted ICER favored CBT over PDT and the adjusted analysis showed that CBT's cost‐effectiveness relative to PDT depends on the willingness to pay (WTP) per AFD. As baseline costs differed substantially the unadjusted estimates might be deceptive. If additional WTPs for CBT of €0, €10, and €30 were assumed, the probability of CBT being cost‐effective relative to PDT was 65, 83, and 96%. Direct costs increased compared to baseline across groups, whereas indirect costs did not change significantly. Results were sensitive to considered costs. Conclusions If the society is willing to pay ≥€30 per additional AFD, CBT can be considered cost‐effective, relative to PDT, with certainty. To further increase the cost‐effectiveness more knowledge regarding predictors of treatment outcome seems essential.

  July 18, 2016   doi: 10.1002/da.22540   open full text
• Parental social networks during childhood and offspring depression in early adulthood: a lifecourse approach.
  Adelyn Allchin, Maria Melchior, Eric Fombonne, Pamela J. Surkan.
  Depression and Anxiety. July 04, 2016
  Background Little is known on how parental social relationships may affect their children's mental health. We sought to examine the relation between parental social relationship characteristics and subsequent offspring depression in young adulthood. Methods We used 2009 Trajectoires Épidémiologiques en Population (TEMPO) study data from 1087 French young adults ages 22 to 35 and parental data from the corresponding Gaz et Eléctricité (GAZEL) study in 1991. Multivariable logistic regression was used to examine parental social networks, quality of parental relationships, and reciprocity of parental social support measured in 1991 in relation to offspring depression in young adulthood measured using the Adult Self Report in 2009. Analyses were stratified by participant sex. Results In adjusted models, daughters of parents who reported giving more support to others than they received had 1.72 higher odds (95% CI, 1.09–2.70) of depression in young adulthood. Daughters of parents who were unsatisfied with their social relationships had 2.14 (95% CI, 1.22–3.76) higher odds of depression. Among male participants, there was no statistically significant association between parental relationship satisfaction, reciprocity of parental exchanges, and depression. Conclusions Parental relationships during mid‐childhood have long‐term associations with offspring depression. Results suggest that enhancing social support for parents may have positive implications for their children's mental health.

  July 04, 2016   doi: 10.1002/da.22538   open full text
• Antidepressant Adherence Across Diverse Populations And Healthcare Settings.
  Rebecca C. Rossom, Susan Shortreed, Karen J. Coleman, Arne Beck, Beth E. Waitzfelder, Christine Stewart, Brian K. Ahmedani, John E. Zeber, Greg E. Simon.
  Depression and Anxiety. June 20, 2016
  Background Early adherence is key to successful depression treatment, but nearly 60% of patients discontinue antidepressants within 3 months. Our study aimed to determine factors associated with poor early adherence to antidepressants in a large diverse sample of patients. Methods Six Mental Health Research Network healthcare systems contributed data for adults with depression and a new antidepressant start, defined by a washout period of at least 270 days, between January 1, 2010 and December 31, 2012. Pharmacy fill and self‐reported race/ethnicity data were obtained from the electronic medical record. Patients had early adherence if they had a second antidepressant fill within 180 days of the first. We used logistic regression to investigate the relationship between early adherence and patient characteristics. Results A total of 177,469 adult patients had 184,967 new episodes of depression with a filled antidepressant prescription. Patients refilled their antidepressants within 180 days in 71% of episodes. Race/ethnicity was a strong predictor of early adherence, with patients from racial/ethnic minorities other than Native Americans/Alaskan Natives less likely (adjusted odd ratios 0.50–0.59) to refill their antidepressants than non‐Hispanic whites. Age, neighborhood education, comorbidity burden, provider type and engagement in psychotherapy were also associated with adherence. Other apparent predictors of early adherence, including neighborhood income, gender, and prior mental health hospitalizations, were no longer significant in the fully adjusted model. Conclusions Race/ethnicity was a robust predictor of early antidepressant adherence, with minority groups other than Native Americans/Alaskan Natives less likely to be adherent. Further research is needed to determine whether early nonadherence in specific minority populations is intentional, due to side effects or patient preference, or unintentional and appropriate for targeted interventions to improve adherence.

  June 20, 2016   doi: 10.1002/da.22532   open full text
• Patterns Of Change In Response To Prolonged Exposure: Implications For Treatment Outcome.
  Joshua D. Clapp, Joshua J. Kemp, Keith S. Cox, Peter W. Tuerk.
  Depression and Anxiety. June 20, 2016
  Background Assessment of response to Prolonged Exposure (PE) suggests some patients may experience discontinuous change involving sudden symptom reductions and/or temporary exacerbations. The current study looked to (1) isolate profiles of PE response among treatment‐seeking veterans and (2) identify factors associated with unique patterns of change. Methods Archival records were examined for veterans receiving PE through a specialty Veterans Affairs Medical Center (VAMC) clinic (N = 109). Latent profile analysis was used to extract response trajectories defined by change in weekly PTSD Checklist (PCL) scores. Associations with provider status (staff vs. intern), setting (in‐person vs. telehealth), initial severity (PTSD; depression), and eventual treatment gains were examined. Results Three profiles were observed. Rapid Responders (18.3%) evidenced sharp reductions at Week 2 and again between Weeks 5 and 6. Linear Responders (40.4%) demonstrated gradual reductions throughout the 10‐week assessment window. Delayed Responder (41.3%) scores were relatively stable over the evaluation period although final session outcomes indicated reliable change (PCLΔ > 10) in 40% of patients. Profiles were similar with respect to provider status, treatment setting, and initial symptom severity. Rapid Responders evidenced lower final session scores relative to Linear (g = 1.13) and Delayed (g = 1.85) groups, with Linear Responders reporting lower end scores than Delayed Responders (g = 1.02). Conclusions Anticipating patterns of recovery and their association with therapeutic outcome is of immense clinical value. Sudden gains emerged as a strong predictor of enhanced response. Data also suggest potential benefits of extending standard intervention for patients who fail to demonstrate an immediate response to PE.

  June 20, 2016   doi: 10.1002/da.22534   open full text
• Randomized Trial Of D‐Cycloserine Enhancement Of Cognitive‐Behavioral Therapy For Panic Disorder.
  Michael W Otto, Mark H Pollack, Sheila M Dowd, Stefan G Hofmann, Godfrey Pearlson, Kristin L Szuhany, Ralitza Gueorguieva, John H Krystal, Naomi M. Simon, David F Tolin.
  Depression and Anxiety. June 17, 2016
  Background Initial studies have provided a mixed perspective of the efficacy of d‐cycloserine (DCS) for augmenting the efficacy of exposure‐based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra‐brief program of CBT. Methods We conducted a double‐blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1‐month, 2‐month, and 6‐month follow‐up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects. Results DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow‐up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition. Conclusions Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow‐up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation.

  June 17, 2016   doi: 10.1002/da.22531   open full text
• Advanced Glycation End Product (AGE) Accumulation in the Skin is Associated with Depression: The Maastricht Study.
  Fleur E. P. Dooren, Frans Pouwer, Casper G. Schalkwijk, Simone J. S. Sep, Coen D. A. Stehouwer, Ronald M. A. Henry, Pieter C. Dagnelie, Nicolaas C. Schaper, Carla J. H. der Kallen, Annemarie Koster, Johan Denollet, Frans R. J. Verhey, Miranda T. Schram.
  Depression and Anxiety. June 06, 2016
  Background Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression. Methods Cross‐sectional data were used from the Maastricht Study (N = 862, mean age 59.8 ± 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein‐bound pentosidine were measured with high‐performance liquid chromatography and fluorescence detection. Nε‐(carboxymethyl)lysine (CML) and Nε‐(carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine‐item Patient Health Questionnaire and the Mini‐International Neuropsychiatric Interview. Results Higher SAF was associated with depressive symptoms (β = 0.42, 95% CI 0.12–0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04–1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder. Conclusions This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression.

  June 06, 2016   doi: 10.1002/da.22527   open full text
• Mid‐Pregnancy Corticotropin‐Releasing Hormone Levels In Association With Postpartum Depressive Symptoms.
  Stavros I. Iliadis, Sara Sylvén, Charlotte Hellgren, Jocelien D. Olivier, Dick Schijven, Erika Comasco, George P. Chrousos, Inger Sundström Poromaa, Alkistis Skalkidou.
  Depression and Anxiety. May 27, 2016
  Background Peripartum depression is a common cause of pregnancy‐ and postpartum‐related morbidity. The production of corticotropin‐releasing hormone (CRH) from the placenta alters the profile of hypothalamus–pituitary–adrenal axis hormones and may be associated with postpartum depression. The purpose of this study was to assess, in nondepressed pregnant women, the possible association between CRH levels in pregnancy and depressive symptoms postpartum. Methods A questionnaire containing demographic data and the Edinburgh Postnatal Depression Scale (EPDS) was filled in gestational weeks 17 and 32, and 6 week postpartum. Blood samples were collected in week 17 for assessment of CRH. A logistic regression model was constructed, using postpartum EPDS score as the dependent variable and log‐transformed CRH levels as the independent variable. Confounding factors were included in the model. Subanalyses after exclusion of study subjects with preterm birth, newborns small for gestational age (SGA), and women on corticosteroids were performed. Results Five hundred thirty‐five women without depressive symptoms during pregnancy were included. Logistic regression showed an association between high CRH levels in gestational week 17 and postpartum depressive symptoms, before and after controlling for several confounders (unadjusted OR = 1.11, 95% CI 1.01–1.22; adjusted OR = 1.13, 95% CI 1.02–1.26; per 0.1 unit increase in log CRH). Exclusion of women with preterm birth and newborns SGA as well as women who used inhalation corticosteroids during pregnancy did not alter the results. Conclusions This study suggests an association between high CRH levels in gestational week 17 and the development of postpartum depressive symptoms, among women without depressive symptoms during pregnancy.

  May 27, 2016   doi: 10.1002/da.22529   open full text
• Accommodation And Treatment Of Anxious Youth.
  Elana R. Kagan, Jeremy S. Peterman, Matthew M. Carper, Philip C. Kendall.
  Depression and Anxiety. May 23, 2016
  Background Parental accommodation refers to the ways in which a parent modifies their behavior to avoid or reduce the distress their child experiences. Parents of youth with anxiety disorders have been found to accommodate their child's anxiety in a variety of ways that contribute to the maintenance of the disorder. The current study evaluated the relationship between parental accommodation and the outcome of treatment for youth with anxiety. Methods Sixty‐two youth (age 6–17) and their parents were evaluated for youth anxiety and parental accommodation before and after treatment. All youth received individual cognitive behavioral therapy (CBT). Results Parental accommodation was significantly reduced from before to after treatment. Reduction in parent‐rated accommodation was significantly associated with the severity of youth's posttreatment anxiety, even when controlling for pretreatment youth anxiety. Level of pretreatment accommodation was significantly associated with treatment response. Conclusions Findings indicate that parental accommodation is significantly reduced after individual youth CBT, and suggest that accommodation may be an important treatment focus. Clinical implications and future directions are discussed.

  May 23, 2016   doi: 10.1002/da.22520   open full text
• Attentional Bias Temporal Dynamics Predict Posttraumatic Stress Symptoms: A Prospective–Longitudinal Study Among Soldiers.
  Judith Schäfer, Amit Bernstein, Ariel Zvielli, Michael Höfler, Hans‐Ulrich Wittchen, Sabine Schönfeld.
  Depression and Anxiety. May 12, 2016
  Background Attentional bias (AB) to threat is thought to play a key role in the development and maintenance of posttraumatic stress symptomatology (PTS). Empirical evidence though is inconsistent. Some studies report associations between AB towards, threat and PTS; other studies report associations between AB away from threat and PTS; yet other studies fail to find any association. We propose that prospective–longitudinal study of AB as a dynamic process, expressed from moment to moment in time, may help to understand these mixed findings and the role of AB in PTS. Methods We tested cross‐sectional and prospective–longitudinal associations between AB and PTS among German soldiers from pre‐ to post‐deployment in Afghanistan (n = 144). AB to threat and positive emotion stimuli (angry/happy faces) was measured using the dot‐probe task. PTS was assessed by the PTSD Checklist. The number of traumatic experiences was assessed using CIDI‐traumatic experience lists for military. Results We found that AB dynamics (i.e., towards, away, temporal variability) at pre‐ and post‐deployment, with respect to angry and happy faces, predicted higher levels of PTS after deployment as a function of number of intermediate traumatic experiences. Traditional aggregated mean bias scores did not similarly prospectively predict PTS post deployment. Conclusions Findings indicate that AB to emotionally arousing stimuli may play an important function in the development and maintenance of PTS. We argue that mixed and null findings appear to be due to failure to model the within‐subject temporal variability in AB expression. Theoretical, empirical, and clinical implications of these findings are discussed.

  May 12, 2016   doi: 10.1002/da.22526   open full text
• Prenatal Exposure To Maternal And Paternal Depressive Symptoms And Brain Morphology: A Population‐Based Prospective Neuroimaging Study In Young Children.
  Hanan El Marroun, Henning Tiemeier, Ryan L. Muetzel, Sandra Thijssen, Noortje J. F. der Knaap, Vincent W. V. Jaddoe, Guillén Fernández, Frank C. Verhulst, Tonya J. H. White.
  Depression and Anxiety. May 10, 2016
  Background Prenatal depressive symptoms have been associated with multiple adverse outcomes. Previously, we demonstrated that prenatal depressive symptoms were associated with impaired growth of the fetus and increased behavioral problems in children aged between 1.5 and 6 years. In this prospective study, we aimed to assess whether prenatal maternal depressive symptoms at 3 years have long‐term consequences on brain development in a cohort of children aged 6–10 years. As a contrast, the association of paternal depressive symptoms during pregnancy and brain morphology was assessed to serve as a marker of background confounding due to shared genetic and environmental family factors. Methods We assessed parental depressive symptoms during pregnancy with the Brief Symptom Inventory. At approximately 8 years of age, we collected structural neuroimaging data, using cortical thickness, surface area, and gyrification as outcomes (n = 654). Results We found that exposure to prenatal maternal depressive symptoms during pregnancy was associated with a thinner superior frontal cortex in the left hemisphere. Additionally, prenatal maternal depressive symptoms were related to larger caudal middle frontal area in the left hemisphere. Maternal depressive symptoms at 3 years were not associated with cortical thickness, surface area, or gyrification in the left and right hemispheres. No effects of paternal depressive symptoms on brain morphology were observed. Conclusions Prenatal maternal depressive symptoms were associated with differences in brain morphology in children. It is important to prevent, identify, and treat depressive symptoms during pregnancy as it may have long‐term consequences on child brain development.

  May 10, 2016   doi: 10.1002/da.22524   open full text
• Comorbid Anxiety and Depression and Their Impact on Cardiovascular Disease in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.
  David G. Bruce, Wendy A. Davis, Milan Dragovic, Timothy M. E. Davis, Sergio E. Starkstein.
  Depression and Anxiety. May 10, 2016
  Background The aims were to determine whether anxious depression, defined by latent class analysis (LCA), predicts cardiovascular outcomes in type 2 diabetes and to compare the predictive power of anxious depression with Diagnostic & Statistical Manual Versions IV and 5 (DSM‐IV/5) categories of depression and generalized anxiety disorder (GAD). Methods Prospective observational study of 1,337 type 2 participants. Baseline assessment with the 9‐item Patient Health Questionnaire and the GAD Scale; LCA‐defined groups with minor or major anxious depression based on anxiety and depression symptoms. Cox modeling used to compare the independent impact of: (1) LCA anxious depression, (2) DSM‐IV/5 depression, (3) GAD on incident cardiovascular events and deaths after 4 years. Results LCA minor and major anxious depression was present in 21.9 and 7.8% of participants, respectively, DSM‐IV/5 minor and major depression in 6.2 and 6.1%, respectively, and GAD in 4.8%. There were 110 deaths, 31 cardiovascular deaths, and 199 participants had incident cardiovascular events. In adjusted models, minor anxious depression (Hazard ratio (95% confidence intervals): 1.70 (1.15–2.50)) and major anxious depression (1.90 (1.11–3.25)) predicted incident cardiovascular events and major anxious depression also predicted cardiovascular mortality (4.32 (1.35–13.86)). By comparison, incident cardiovascular events were predicted by DSM‐IV/5 major depression (2.10 (1.22–3.62)) only and cardiovascular mortality was predicted by both DSM‐IV/5 major depression (3.56 (1.03–12.35)) and GAD (5.92 (1.84–19.08)). Conclusions LCA‐defined anxious depression is more common than DSM‐IV/5 categories and is a strong predictor of cardiovascular outcomes in type 2 diabetes. These data suggest that this diagnostic scheme has predictive validity and clinical relevance.

  May 10, 2016   doi: 10.1002/da.22523   open full text
• Improvements In Psychosocial Functioning And Health‐Related Quality Of Life Following Exercise Augmentation In Patients With Treatment Response But Nonremitted Major Depressive Disorder: Results From The Tread Study.
  Tracy L. Greer, Joseph M. Trombello, Chad D. Rethorst, Thomas J. Carmody, Manish K. Jha, Allen Liao, Bruce D. Grannemann, Heather O. Chambliss, Timothy S. Church, Madhukar H. Trivedi.
  Depression and Anxiety. May 10, 2016
  Background Functional impairments often remain despite symptomatic improvement with antidepressant treatment, supporting the need for novel treatment approaches. The present study examined the extent to which exercise augmentation improved several domains of psychosocial functioning and quality of life (QoL) among depressed participants. Methods Data were collected from 122 partial responders to antidepressant medication. Participants were randomized to either high‐ (16 kcal/kg of weight/week [KKW]) or low‐dose (4‐KKW) exercise. Participants completed a combination of supervised and home‐based exercise for 12 weeks. The Short‐Form Health Survey, Work and Social Adjustment Scale, Social Adjustment Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and Satisfaction with Life Scale were collected at 6 and 12 weeks. Participants with data for at least one of the two follow‐up time points (n = 106) were analyzed using a linear mixed model to assess change from baseline within groups and the difference between groups for each psychosocial outcome measure. All analyses controlled for covariates, including baseline depressive symptomatology. Results Participants experienced significant improvements in functioning across tested domains, and generally fell within a healthy range of functioning on all measures at Weeks 6 and 12. Although no differences were found between exercise groups, improvements were observed across a variety of psychosocial and QoL domains, even in the low‐dose exercise group. Conclusions These findings support exercise augmentation of antidepressant treatment as a viable intervention for treatment‐resistant depression to improve function in addition to symptoms.

  May 10, 2016   doi: 10.1002/da.22521   open full text
• Naturalistic Course Of Major Depressive Disorder Predicted By Clinical And Structural Neuroimaging Data: A 5‐Year Follow‐Up.
  Maria Serra‐Blasco, Javier Diego‐Adeliño, Yolanda Vives‐Gilabert, Joan Trujols, Dolors Puigdemont, Mar Carceller‐Sindreu, Victor Pérez, Enric Álvarez, Maria J. Portella.
  Depression and Anxiety. May 09, 2016
  Background Despite its high recurrence rate, major depression disorder (MDD) still lacks neurobiological markers to optimize treatment selection. The aim of this study was to examine the prognostic potential of clinical and structural magnetic resonance imaging (sMRI) in the long‐term MDD clinical outcomes (COs). Methods Forty‐nine MDD patients were grouped into one of four different CO categories according to their trajectory: recovery, partial remission, remission recurrence, and chronic depression. Regression models including baseline demographic, clinical, and sMRI data were used for predicting patients' COs and symptom severity 5 years later. Results The model including only clinical data explained 32.4% of the variance in COs and 55% in HDRS, whereas the model combining clinical and sMRI data increased up to 52/68%, respectively. A bigger volume of right anterior cingulate gyrus was the variable that best predicted COs. Conclusions The findings suggest that the addition of sMRI brain data to clinical information in depressive patients can significantly improve the prediction of their COs. The dorsal part of the right anterior cingulate gyrus may act as a potential biomarker of long‐term clinical trajectories.

  May 09, 2016   doi: 10.1002/da.22522   open full text
• Psychotherapy Versus Pharmacotherapy For Posttraumatic Stress Disorder: Systemic Review And Meta‐Analyses To Determine First‐Line Treatments.
  Daniel J. Lee, Carla W. Schnitzlein, Jonathan P. Wolf, Meena Vythilingam, Ann M. Rasmusson, Charles W. Hoge.
  Depression and Anxiety. April 29, 2016
  Background Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first‐line treatment. Direct head‐to‐head comparisons are lacking. Methods Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview‐based outcome measures, active‐control conditions (e.g. supportive psychotherapy), and intent‐to‐treat analysis were selected for analyses. Independent review, data abstraction, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow‐up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta‐analyses for medication versus control, medication pre‐/posttreatment, psychotherapy versus control, and psychotherapy pre‐/posttreatment. Results Effect sizes for trauma‐focused psychotherapies (TFPs) versus active control conditions were greater than medications versus placebo and other psychotherapies versus active controls. TFPs resulted in greater sustained benefit over time than medications. Sertraline, venlafaxine, and nefazodone outperformed other medications, although potential for methodological biases were high. Improvement following paroxetine and fluoxetine treatment was small. Venlafaxine and stress inoculation training (SIT) demonstrated large initial effects that decreased over time. Bupropion, citalopram, divalproex, mirtazapine, tiagabine, and topiramate failed to differentiate from placebo. Aripiprazole, divalproex, guanfacine, and olanzapine failed to differentiate from placebo when combined with an antidepressant. Conclusions Study findings support use of TFPs over nontrauma‐focused psychotherapy or medication as first‐line interventions. Second‐line interventions include SIT, and potentially sertraline or venlafaxine, rather than entire classes of medication, such as SSRIs. Future revisions of CPGs should prioritize studies that utilize active controls over waitlist or treatment‐as‐usual conditions. Direct head‐to‐head trials of TFPs versus sertraline or venlafaxine are needed.

  April 29, 2016   doi: 10.1002/da.22511   open full text
• Bidirectional Prospective Associations Of Metabolic Syndrome Components With Depression, Anxiety, And Antidepressant Use.
  Sarah A. Hiles, Dóra Révész, Femke Lamers, Erik Giltay, Brenda W. J. H. Penninx.
  Depression and Anxiety. April 27, 2016
  Background Metabolic syndrome components—waist circumference, high‐density lipoprotein cholesterol (HDL‐C), triglycerides, systolic blood pressure and fasting glucose—are cross‐sectionally associated with depression and anxiety with differing strength. Few studies examine the relationships over time or whether antidepressants have independent effects. Methods Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2,776; 18–65 years; 66% female). At baseline, 2‐ and 6‐year follow‐up, participants completed diagnostic interviews, depression and anxiety symptom inventories, antidepressant use assessment, and measurements of the five metabolic syndrome components. Data were analyzed for the consistency of associations between psychopathology indicators and metabolic syndrome components across the three assessment waves, and whether psychopathology or antidepressant use at one assessment predicts metabolic dysregulation at the next and vice versa. Results Consistently across waves, psychopathology was associated with generally poorer values of metabolic syndrome components, particularly waist circumference and triglycerides. Stronger associations were observed for psychopathology symptom severity than diagnosis. Antidepressant use was independently associated with higher waist circumference, triglycerides and number of metabolic syndrome abnormalities, and lower HDL‐C. Symptom severity and antidepressant use were associated with subsequently increased number of abnormalities, waist circumference, and glucose after 2 but not 4 years. Conversely, there was little evidence that metabolic syndrome components were associated with subsequent psychopathology outcomes. Conclusions Symptom severity and antidepressant use were independently associated with metabolic dysregulation consistently over time and also had negative consequences for short‐term metabolic health. This is of concern given the chronicity of depression and anxiety and prevalence of antidepressant treatment.

  April 27, 2016   doi: 10.1002/da.22512   open full text
• Self‐Rated Expectations Of Suicidal Behavior Predict Future Suicide Attempts Among Adolescent And Young Adult Psychiatric Emergency Patients.
  Ewa K. Czyz, Adam G. Horwitz, Cheryl A. King.
  Depression and Anxiety. April 25, 2016
  Background This study's purpose was to examine the predictive validity and clinical utility of a brief measure assessing youths’ own expectations of their future risk of suicidal behavior, administered in a psychiatric emergency (PE) department; and determine if youths’ ratings improve upon a clinician‐administered assessment of suicidal ideation severity. The outcome was suicide attempts up to 18 months later. Methods In this medical record review study, 340 consecutively presenting youths (ages 13–24) seeking PE services over a 7‐month period were included. Subsequent PE visits and suicide attempts were retrospectively tracked for up to 18 months. The 3‐item scale assessing patients’ perception of their own suicidal behavior risk and the clinician‐administered ideation severity scale were used routinely at the study site. Results Cox regression results showed that youths’ expectations of suicidal behavior were independently associated with increased risk of suicide attempts, even after adjusting for key covariates. Results were not moderated by sex, suicide attempt history, or age. Receiver‐operating characteristic (ROC) analyses indicated that self‐assessed expectations of risk improved the predictive accuracy of the clinician‐administered suicidal ideation measure. Conclusions Youths’ ratings indicative of lower confidence in maintaining safety uniquely predicted follow‐up attempts and provided incremental validity over and above the clinician‐administered assessment and improved its accuracy, suggesting their potential for augmenting suicide risk formulation. Assessing youths’ own perceptions of suicide risk appears to be clinically useful, feasible to implement in PE settings, and, if replicated, promising for improving identification of youth at risk for suicidal behavior.

  April 25, 2016   doi: 10.1002/da.22514   open full text
• Anxiety Patients Show Reduced Working Memory Related dlPFC Activation During Safety and Threat.
  Nicholas L. Balderston, Katherine E. Vytal, Katherine O'Connell, Salvatore Torrisi, Allison Letkiewicz, Monique Ernst, Christian Grillon.
  Depression and Anxiety. April 25, 2016
  Background Anxiety patients exhibit deficits in cognitive tasks that require prefrontal control of attention, including those that tap working memory (WM). However, it is unclear whether these deficits reflect threat‐related processes or symptoms of the disorder. Here, we distinguish between these hypotheses by determining the effect of shock threat versus safety on the neural substrates of WM performance in anxiety patients and healthy controls. Methods Patients, diagnosed with generalized and/or social anxiety disorder, and controls performed blocks of an N‐back WM task during periods of safety and threat of shock. We recorded blood‐oxygen‐level dependent (BOLD) activity during the task, and investigated the effect of clinical anxiety (patients vs. controls) and threat on WM load‐related BOLD activation. Results Behaviorally, patients showed an overall impairment in both accuracy and reaction time compared to controls, independent of threat. At the neural level, patients showed less WM load‐related activation in the dorsolateral prefrontal cortex, a region critical for cognitive control. In addition, patients showed less WM load‐related deactivation in the ventromedial prefrontal cortex and posterior cingulate cortex, which are regions of the default mode network. Most importantly, these effects were not modulated by threat. Conclusions This work suggests that the cognitive deficits seen in anxiety patients may represent a key component of clinical anxiety, rather than a consequence of threat.

  April 25, 2016   doi: 10.1002/da.22518   open full text
• Chronicity Of Depression And Molecular Markers In A Large Sample Of Han Chinese Women.
  Alexis C. Edwards, Steven H. Aggen, Na Cai, Tim B. Bigdeli, Roseann E. Peterson, Anna R. Docherty, Bradley T. Webb, Silviu‐Alin Bacanu, Jonathan Flint, Kenneth S. Kendler.
  Depression and Anxiety. April 25, 2016
  Background Major depressive disorder (MDD) has been associated with changes in mean telomere length and mitochondrial DNA (mtDNA) copy number. This study investigates if clinical features of MDD differentially impact these molecular markers. Methods Data from a large, clinically ascertained sample of Han Chinese women with recurrent MDD were used to examine whether symptom presentation, severity, and comorbidity were related to salivary telomere length and/or mtDNA copy number (maximum N = 5,284 for both molecular and phenotypic data). Results Structural equation modeling revealed that duration of longest episode was positively associated with mtDNA copy number, while earlier age of onset of most severe episode and a history of dysthymia were associated with shorter telomeres. Other factors, such as symptom presentation, family history of depression, and other comorbid internalizing disorders, were not associated with these molecular markers. Conclusions Chronicity of depressive symptoms is related to more pronounced telomere shortening and increased mtDNA copy number among individuals with a history of recurrent MDD. As these molecular markers have previously been implicated in physiological aging and morbidity, individuals who experience prolonged depressive symptoms are potentially at greater risk of adverse medical outcomes.

  April 25, 2016   doi: 10.1002/da.22517   open full text
• A Dilemma‐Focused Intervention For Depression: A Multicenter, Randomized Controlled Trial With A 3‐Month Follow‐Up.
  Guillem Feixas, Arturo Bados, Eugeni García‐Grau, Clara Paz, Adrián Montesano, Victoria Compañ, Marta Salla, Mari Aguilera, Adriana Trujillo, José Cañete, Leticia Medeiros‐Ferreira, José Soriano, Montserrat Ibarra, Joan C. Medina, Eliana Ortíz, Fernando Lana.
  Depression and Anxiety. April 22, 2016
  Background Since long ago it has been asserted that internal conflicts are relevant to the understanding and treatment of mental disorders, but little research has been conducted to support the claim. The aim of this study was to test the differential efficacy of group cognitive behavioral therapy (CBT) plus an intervention focused on the dilemma(s) detected for each patient versus group individual CBT plus individual CBT for treating depression. A comparative controlled trial with a 3‐month follow‐up was conducted. Methods One hundred twenty‐eight adults meeting criteria for MDD and/or dysthymia, presenting at least one cognitive conflict (implicative dilemma or dilemmatic construct, assessed by the repertory grid technique) and who had completed seven sessions of group CBT were randomly assigned to eight sessions of individual manualized CBT or dilemma‐focused therapy (DFT). The Beck Depression Inventory‐II was administered at baseline, at the end of therapy and after 3 months’ follow‐up. Results Multilevel mixed effects modeling yielded no significant differences between CBT and DFT with the intention‐to‐treat sample. Equivalent effect sizes, remission, and response rates were found with completers as well. In combination with group CBT, both individual CBT and DFT significantly reduced depressive symptoms. Conclusions Both conditions obtained comparable results to those in the literature. Thus, the superiority of the adjunctive DFT was not demonstrated. Working with dilemmas can be seen as a promising additional target in the psychotherapy of depression, but further research is still required.

  April 22, 2016   doi: 10.1002/da.22510   open full text
• Neuropsychological Predictors Of Treatment Response To Cognitive Behavioral Group Therapy In Obsessive–Compulsive Disorder.
  Daniela T. Braga, Amitai Abramovitch, Leonardo F. Fontenelle, Ygor A. Ferrão, Juliana B. Gomes, Analise S. Vivan, Kimberly K. Ecker, Cristiane F. Bortoncello, Andrew Mittelman, Euripides C. Miguel, Clarissa M. Trentini, Aristides V. Cordioli.
  Depression and Anxiety. April 21, 2016
  Background The available research on the relationship between neuropsychological functioning and the therapeutic outcome of obsessive–compulsive disorder (OCD) has yielded inconsistent results. In this study, our aim was twofold. First, we sought to evaluate the effects of cognitive behavioral group therapy (CBGT) on neurocognitive functions in OCD patients. Second, we assessed the viability of neuropsychological test performance as a predictor of treatment response to CBGT. Methods One hundred fifty carefully screened OCD patients were randomized to receive either 12‐week CBGT (n = 75) or to remain on a waiting list (WL; n = 75) for the corresponding time. Forty‐seven participants dropped out of the study, leaving 103 participants that were included in the analysis (CBGT, n = 61; WL, n = 42). Participants had several neuropsychological domains evaluated both at baseline and at end‐point. Results A significant difference in obsessive–compulsive, anxiety, and depression symptoms was observed between treated patients and controls favoring the CBGT group, but no significant differences were found on neuropsychological measures after 3 months of CBGT. In addition, there were no differences between treatment responders and nonresponders on all neuropsychological outcome measures. Employing a conservative alpha, neuropsychological test performance did not predict CBGT treatment response. Conclusions Although the CBGT group demonstrated significant improvement in OCD symptoms, no significant difference was found on all neuropsychological domains, and test performance did not predict treatment response.

  April 21, 2016   doi: 10.1002/da.22509   open full text
• Nut Consumption Is Associated With Depressive Symptoms Among Chinese Adults.
  Qian Su, Bin Yu, Haiyan He, Qing Zhang, Ge Meng, Hongmei Wu, Huanmin Du, Li Liu, Hongbin Shi, Yang Xia, Xiaoyan Guo, Xing Liu, Chunlei Li, Xue Bao, Yeqing Gu, Liyun Fang, Fei Yu, Huijun Yang, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Honglin Zhao, Kun Song, Kaijun Niu.
  Depression and Anxiety. April 20, 2016
  Background Affective disorders, especially depressive symptoms, bring such a burden to mortality and morbidity that they are associated with physical and psychological health and quality of life. Nuts, a foodstuff rich in multiple micronutrients, macronutrients, and other useful components, were considered to be a protector against depressive symptoms. Here, we conducted an analysis to examine the relationship between nut consumption and depressive symptoms. Methods The study performed a cross‐sectional study to examine whether nut consumption is related to depressive symptoms among 13,626 inhabitants in Tianjin. Nut consumption was assessed using a validated food frequency questionnaire and depressive symptoms was assessed using the Chinese version of 20‐item Self‐rating Depression Scale (SDS) with four cutoffs (40, 45, 48, and 50) to indicate elevated depressive symptoms. Results The prevalence of depressive symptoms was 38.7, 19.1, 11.4, and 7.3% for SDS ≥40, 45, 48, and 50, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence interval) of having elevated depressive symptoms with SDS ≥40 by increasing frequency of nut consumption were 1.00 for

  April 20, 2016   doi: 10.1002/da.22516   open full text
• Educational Attainment As A Protective Factor For Psychiatric Disorders: Findings From A Nationally Representative Longitudinal Study.
  Julie Erickson, Renée El‐Gabalawy, Daniel Palitsky, Scott Patten, Corey S. Mackenzie, Murray B. Stein, Jitender Sareen.
  Depression and Anxiety. April 20, 2016
  Objective This study examined cross‐sectional and longitudinal relationships between educational attainment and psychiatric disorders (i.e., mood, anxiety, substance use, and personality disorders) using a nationally representative survey of US adults. Method We used data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). Bivariate and multiple logistic regressions examined cross‐sectional and longitudinal associations between educational attainment and a variety of past‐year and incident anxiety, mood, and substance use disorders, controlling for sociodemographics and psychiatric disorder comorbidity. Results Adjusted cross‐sectional data indicated that educational attainment below a graduate or professional degree at Wave 2 was associated with significantly higher odds of substance use and/or dependence disorders (adjusted odds ratio range (AORR = 1.55–2.55, P < 0.001). Longitudinal adjusted regression analyses indicated that individuals reporting less than a college education at Wave 1 were at significantly higher odds of experiencing any incident mood (AORR 1.49–1.64, P < 0.01), anxiety (AORR 1.35–1.69, P < 0.01), and substance use disorder (AORR 1.50–2.02, P < 0.01) at Wave 2 even after controlling for other sociodemographic variables and psychiatric comorbidity. Conclusion Findings lend support to other published research demonstrating that educational attainment is protective against developing a spectrum of psychiatric disorders. Mechanisms underlying this relationship are speculative and in need of additional research.

  April 20, 2016   doi: 10.1002/da.22515   open full text
• Inflexible Cognition Predicts First Onset Of Major Depressive Episodes In Adolescence.
  Jonathan P. Stange, Samantha L. Connolly, Taylor A. Burke, Jessica L. Hamilton, Elissa J. Hamlat, Lyn Y. Abramson, Lauren B. Alloy.
  Depression and Anxiety. April 19, 2016
  Background Major depressive disorder often is characterized by a lack of cognitive and emotional flexibility, resulting in an impaired ability to adapt to situational demands. Adolescence is an important period of risk for the first onset of depression, yet relatively little is known about whether aspects of inflexibility, such as rumination and deficits in attentional shifting, could confer risk for the development of the disorder during this time. Method In the present study, a sample of 285 never‐depressed adolescents completed self‐report and behavioral measures of rumination and attentional shifting at a baseline visit, followed by up to 4 years of annual prospective follow‐up diagnostic assessments. Results Survival analyses indicated that adolescents with greater levels of rumination or poorer attentional shifting experienced a shorter time until the first onset of major depressive episodes, even after accounting for baseline symptoms and demographic characteristics. Although girls were twice as likely as boys to experience the first onset of depression, rumination predicted a shorter time until depression onset only for boys. Rumination and attentional shifting were not correlated and predicted time until onset of major depression independently of one another. Conclusions These results provide evidence that components of cognition that are characterized by rigidity and perseveration confer risk for the first onset of major depression during adolescence. Evaluating rumination and attentional shifting in adolescence may be useful in identifying individuals who are at risk for depression and who may benefit from interventions that target or alter the development of these characteristics.

  April 19, 2016   doi: 10.1002/da.22513   open full text
• Altered Topography Of Intrinsic Functional Connectivity In Childhood Risk For Social Anxiety.
  Bradley C. Taber‐Thomas, Santiago Morales, Frank G. Hillary, Koraly E. Pérez‐Edgar.
  Depression and Anxiety. April 19, 2016
  Background Extreme shyness in childhood arising from behavioral inhibition (BI) is among the strongest risk factors for developing social anxiety. Although no imaging studies of intrinsic brain networks in children with BI have been reported, adults with a history of BI exhibit altered functioning of frontolimbic circuits and enhanced processing of salient, personally relevant information. BI in childhood may be marked by increased coupling of salience (insula) and default (ventromedial prefrontal cortex [vmPFC]) network hubs. Methods We tested this potential relation in 42 children ages 9–12, oversampled for high BI. Participants provided resting‐state functional magnetic resonance imaging. A novel topographical pattern analysis of salience network intrinsic functional connectivity was conducted, and the impact of salience–default coupling on the relation between BI and social anxiety symptoms was assessed via moderation analysis. Results Children with high BI exhibit altered salience network topography, marked by reduced insula connectivity to dorsal anterior cingulate and increased insula connectivity to vmPFC. Whole‐brain analyses revealed increased connectivity of salience, executive, and sensory networks with default network hubs in children higher in BI. Finally, the relation between insula‐ventromedial prefrontal connectivity and social anxiety symptoms was strongest among the children highest in BI. Conclusions BI is associated with an increase in connectivity to default network hubs that may bias processing toward personally relevant information during development. These altered patterns of connectivity point to potential biomarkers of the neural profile of risk for anxiety in childhood.

  April 19, 2016   doi: 10.1002/da.22508   open full text
• Childhood Maltreatment Predicts Reduced Inhibition‐Related Activity In The Rostral Anterior Cingulate In Ptsd, But Not Trauma‐Exposed Controls.
  Jennifer S. Stevens, Timothy D. Ely, Takehito Sawamura, Dora Guzman, Bekh Bradley, Kerry J. Ressler, Tanja Jovanovic.
  Depression and Anxiety. April 08, 2016
  Background A deficit in the ability to inhibit fear has been proposed as a biomarker of posttraumatic stress disorder (PTSD). Previous research indicates that individuals with PTSD show reduced inhibition‐related activation in rostral anterior cingulate cortex (rACC). The goal of the current study was to investigate differential influences of an early environmental risk factor for PTSD—childhood maltreatment—on inhibition‐related brain function in individuals with PTSD versus trauma‐exposed controls. Methods Individuals with PTSD (n = 37) and trauma‐exposed controls (n = 53) were recruited from the primary care waiting rooms of an urban public hospital in Atlanta, GA. Participants completed an inhibition task during fMRI, and reported childhood and adult traumatic experiences. The groups were matched for adult and child trauma load. Results We observed an interaction between childhood maltreatment severity and PTSD status in the rACC (P < .05, corrected), such that maltreatment was negatively associated with inhibition‐related rACC activation in the PTSD group, but did not influence rACC activation in the TC group. Rostral ACC activation was associated with inhibition‐related task performance in the TC group but not the PTSD group, suggesting a possible contribution to stress resilience. Conclusions Findings highlight individual differences in neural function following childhood trauma, and point to inhibition‐related activation in rostral ACC as a risk factor for PTSD.

  April 08, 2016   doi: 10.1002/da.22506   open full text
• A Brief Ecological Momentary Intervention For Generalized Anxiety Disorder: A Randomized Controlled Trial Of The Worry Outcome Journal.
  Lucas S. LaFreniere, Michelle G. Newman.
  Depression and Anxiety. April 07, 2016
  Background The efficacy of many cognitive behavioral component interventions has not been examined, with worry outcome monitoring among them. Methods To address this issue, 51 participants with clinical levels of generalized anxiety disorder were randomly assigned to a treatment or control condition for 10 days. The treatment condition consisted of a brief ecological momentary intervention termed the Worry Outcome Journal (WOJ). WOJ participants recorded worries and tracked their outcomes, rating worry distress, interference, and expected outcome probabilities. Thought log (TL) control participants completed a record of their everyday thoughts and rated associated distress. All participants made four entries on paper each day when randomly prompted by text message. They then entered their paper contents online each night. After 30 days they reviewed their contents electronically and completed follow‐up measures. Results Primary results revealed significant reductions in worry for WOJ users compared to TL users at postintervention. A marginally significant difference was found at 20‐day follow‐up and treatment gains were maintained. Secondary analyses showed no harmful increases in worry beliefs for WOJ users, as well as preliminary evidence for decreases in beliefs about the uncontrollability of thoughts in both groups. Conclusion The WOJ may be a viable therapist‐independent treatment for reducing worry, even after only 10 days of use.

  April 07, 2016   doi: 10.1002/da.22507   open full text
• A STUDY OF THE PATTERN OF RESPONSE TO rTMS TREATMENT IN DEPRESSION.
  Paul B. Fitzgerald, Kate E. Hoy, Rodney J. Anderson, Zafiris J. Daskalakis.
  Depression and Anxiety. April 05, 2016
  Background Considerable research has demonstrated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment in patients with depression. However, limited research has described the pattern of response to rTMS treatment or explored possible predictors of the likelihood of treatment response. Methods Data from 11 clinical trials (n = 1,132) was pooled and we described the pattern of response to rTMS, rate of response, and remission as well as potential clinical and demographic predictors of response. Results There was a bimodal pattern of response to rTMS with the response‐associated peak at 57% reduction in depression rating scale scores. About 46% of patients achieved response criteria, with 31% completing rTMS treatment in remission. A greater likelihood of response was seen for patients who had less severe depression at baseline, a shorter duration of the current episode, and recurrent rather than single episode of depression. Greater response was also seen in patients treated at higher stimulation intensity. Conclusions A meaningful percentage (>40%) of patients respond to a course of rTMS treatment. Response does vary with a number of clinical and demographic variables but none of these variables exert a sufficiently strong influence on response rates to warrant using these criteria to exclude patients from treatment.

  April 05, 2016   doi: 10.1002/da.22503   open full text
• Child Sexual Abuse, Bullying, Cyberbullying, And Mental Health Problems Among High Schools Students: A Moderated Mediated Model.
  Martine Hébert, Jude Mary Cénat, Martin Blais, Francine Lavoie, Mireille Guerrier.
  Depression and Anxiety. April 01, 2016
  Background Child sexual abuse is associated with adverse outcomes, including heightened vulnerability that may translate into risk of revictimization. The aims of the study were: (1) to explore the direct and indirect links between child sexual abuse and cyberbullying, bullying, and mental health problems and (2) to study maternal support as a potential protective factor. Methods Teenagers involved in the two first waves of the Quebec Youths' Romantic Relationships Survey (N = 8,194 and 6,780 at Wave I and II, respectively) completed measures assessing child sexual abuse and maternal support at Wave I. Cyberbullying, bullying, and mental health problems (self‐esteem, psychological distress, and suicidal ideations) were evaluated 6 months later. Results Rates of cyberbullying in the past 6 months were twice as high in sexually abused teens compared to nonvictims both for girls (33.47 vs. 17.75%) and boys (29.62 vs. 13.29%). A moderated mediated model revealed a partial mediation effect of cyberbullying and bullying in the link between child sexual abuse and mental health. Maternal support acted as a protective factor as the conditional indirect effects of child sexual abuse on mental health via cyberbullying and bullying were reduced in cases of high maternal support. Conclusions Results have significant relevance for prevention and intervention in highlighting the heightened vulnerability of victims of child sexual abuse to experience both bullying and cyberbullying. Maternal support may buffer the risk of developing mental health distress, suggesting that intervention programs for victimized youth may profit by fostering parent involvement.

  April 01, 2016   doi: 10.1002/da.22504   open full text
• Glucocorticoid Receptor‐Related Genes: Genotype And Brain Gene Expression Relationships To Suicide And Major Depressive Disorder.
  Honglei Yin, Hanga Galfalvy, Spiro P. Pantazatos, Yung‐yu Huang, Gorazd B. Rosoklija, Andrew J. Dwork, Ainsley Burke, Victoria Arango, Maria A. Oquendo, J. John Mann.
  Depression and Anxiety. March 31, 2016
  Introduction We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic‐pituitary‐adrenal axis, suicidal behavior, and MDD; FK506‐binding protein 5 (FKBP5), Spindle and kinetochore‐associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). Materials and Methods Single‐nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209). RNA‐seq was used to examine gene and isoform‐level brain expression postmortem (Brodmann Area 9; N = 59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). Results We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, which was associated with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs on this gene, three SNPs on SKA2, and one near NR3C1 showed before‐adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript had lower expression in suicide relative to nonsuicide sudden death cases (b = −0.48, SE = 0.12, t = −4.02, adjusted P = .004). Conclusion We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the pFCTX. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior.

  March 31, 2016   doi: 10.1002/da.22499   open full text
• Morbid Thoughts And Suicidal Ideation In Iraq War Veterans: The Role Of Direct And Indirect Killing In Combat.
  Anna Kline, Marc D. Weiner, Alejandro Interian, Anton Shcherbakov, Lauren St. Hill.
  Depression and Anxiety. March 31, 2016
  Background Although research has identified numerous risk factors for military suicide, the contribution of combat exposure to suicide risk has not been clearly established. Previous studies finding no association of suicidality with combat exposure have employed overgeneral measures of exposure, which do not differentiate among the varieties of combat experiences. This study disaggregated the forms of combat exposure to assess the contribution of combat‐related killing to morbid thoughts and suicidal ideation (MTSI) in National Guard troops deployed to Iraq. Methods We conducted parallel analyses of two related samples: a cross‐sectional sample (n = 1,665) having postdeployment interview data only and a longitudinal subsample (n = 922) having pre‐ and postdeployment data. We used multiple logistic regression to examine the role of killing‐related exposures, after controlling for general combat and other suicide risks, and examined interactions between killing and other suicide vulnerability factors. Results Killing‐related exposure approximately doubled the risk of MTSI in the cross‐sectional multivariate model (Adjusted Odds Ratio [AOR] = 1.87; CI = 1.26–2.78) and the longitudinal model (AOR = 2.02; CI = 1.06–3.85), which also controlled for predeployment risks. Killing exposures further increased the MTSI risk associated with other suicide vulnerability factors, including depression (AOR = 14.89 for depression and killing vs. AOR = 9.92 for depression alone), alcohol dependence (AOR = 5.63 for alcohol and killing vs. 1.91 for alcohol alone), and readjustment stress (AOR = 4.90 for stress and killing vs. 1.48 for stress alone). General combat exposure had no comparable effects. Conclusions The findings underscore a need for assessment and treatment protocols that address the psychological effects of killing‐related and other potentially “morally injurious” experiences among combat soldiers.

  March 31, 2016   doi: 10.1002/da.22496   open full text
• Individualized Yoga For Reducing Depression And Anxiety, And Improving Well‐Being: A Randomized Controlled Trial.
  Michael Manincor, Alan Bensoussan, Caroline A. Smith, Kylie Barr, Monica Schweickle, Lee‐Lee Donoghoe, Suzannah Bourchier, Paul Fahey.
  Depression and Anxiety. March 31, 2016
  Background Depression and anxiety are leading causes of disability worldwide. Current treatments are primarily pharmaceutical and psychological. Questions remain about effectiveness and suitability for different people. Previous research suggests potential benefits of yoga for reducing depression and anxiety. The aim of this study is to investigate the effects of an individualized yoga intervention. Methods A sample of 101 people with symptoms of depression and/or anxiety participated in a randomized controlled trial comparing a 6‐week yoga intervention with waitlist control. Yoga was additional to usual treatment. The control group was offered the yoga following the waitlist period. Measures included Depression Anxiety Stress Scale (DASS‐21), Kessler Psychological Distress Scale (K10), Short‐Form Health Survey (SF12), Scale of Positive and Negative Experience (SPANE), Flourishing Scale (FS), and Connor‐Davidson Resilience Scale (CD‐RISC2). Results There were statistically significant differences between yoga and control groups on reduction of depression scores (−4.30; 95% CI: −7.70, −0.01; P = .01; ES −.44). Differences in reduced anxiety scores were not statistically significant (−1.91; 95% CI: −4.58, 0.76; P = .16). Statistically significant differences in favor of yoga were also found on total DASS (P = .03), K10, SF12 mental health, SPANE, FS, and resilience scores (P < .01 for each). Differences in stress and SF12 physical health scores were not statistically significant. Benefits were maintained at 6‐week follow‐up. Conclusion Yoga plus regular care was effective in reducing symptoms of depression compared with regular care alone. Further investigation is warranted regarding potential benefits in anxiety. Individualized yoga may be particularly beneficial in mental health care in the broader community.

  March 31, 2016   doi: 10.1002/da.22502   open full text
• Randomized Trial of Interpersonal Psychotherapy and Cognitive Behavioral Therapy for Major Depressive Disorder in a Community‐Based Psychiatric Outpatient Clinic.
  Annika Ekeblad, Fredrik Falkenström, Gerhard Andersson, Robert Vestberg, Rolf Holmqvist.
  Depression and Anxiety. March 31, 2016
  Background Interpersonal psychotherapy (IPT) and cognitive behavioral therapy (CBT) are both evidence‐based treatments for major depressive disorder (MDD). Several head‐to‐head comparisons have been made, mostly in the United States. In this trial, we compared the two treatments in a small‐town outpatient psychiatric clinic in Sweden. The patients had failed previous primary care treatment and had extensive Axis‐II comorbidity. Outcome measures were reduction of depressive symptoms and attrition rate. Methods Ninety‐six psychiatric patients with MDD (DSM‐IV) were randomized to 14 sessions of CBT (n = 48) or IPT (n = 48). A noninferiority design was used with the hypothesis that IPT would be noninferior to CBT. A three‐point difference on the Beck Depression Inventory‐II (BDI‐II) was used as noninferiority margin. Results IPT passed the noninferiority test. In the ITT group, 53.5% (23/43) of the IPT patients and 51.0% (24/47) of the CBT patients were reliably improved, and 20.9% (9/43) and 19.1% (9/47), respectively, were recovered (last BDI score <10). The dropout rate was significantly higher in CBT (40%; 19/47) compared to IPT (19%; 8/43). Statistically controlling for antidepressant medication use did not change the results. Conclusions IPT was noninferior to CBT in a sample of depressed psychiatric patients in a community‐based outpatient clinic. CBT had significantly more dropouts than IPT, indicating that CBT may be experienced as too demanding. Since about half the patients did not recover, there is a need for further treatment development for these patients. The study should be considered an effectiveness trial, with strong external validity but some limitations in internal validity.

  March 31, 2016   doi: 10.1002/da.22495   open full text
• Posttraumatic Stress Symptoms And Aversion To Ambiguous Losses In Combat Veterans.
  Lital Ruderman, Daniel B. Ehrlich, Alicia Roy, Robert H. Pietrzak, Ilan Harpaz‐Rotem, Ifat Levy.
  Depression and Anxiety. March 21, 2016
  Background Psychiatric symptoms typically cut across traditional diagnostic categories. In order to devise individually tailored treatments, there is a need to identify the basic mechanisms that underlie these symptoms. Behavioral economics provides a framework for studying these mechanisms at the behavioral level. Here, we utilized this framework to examine a widely ignored aspect of trauma‐related symptomatology—individual uncertainty attitudes—in combat veterans with and without posttraumatic stress disorder (PTSD). Methods Fifty‐seven combat veterans, including 30 with PTSD and 27 without PTSD, completed a risk and ambiguity decision‐making task that characterizes individual uncertainty attitudes, distinguishing between attitudes toward uncertain outcomes with known (“risk”) and unknown (“ambiguity”) probabilities, and between attitudes toward uncertain gains and uncertain losses. Participants’ choices were used to estimate risk and ambiguity attitudes in the gain and loss domains. Results Veterans with PTSD were more averse to ambiguity, but not risk, compared to veterans without PTSD, when making choices between possible losses, but not gains. The degree of aversion was associated with anxious arousal (e.g., hypervigilance) symptoms, as well as with the degree of combat exposure. Moreover, ambiguity attitudes fully mediated the association between combat exposure and anxious arousal symptoms. Conclusions These results provide a foundation for prospective studies of the causal association between ambiguity attitudes and trauma‐related symptoms, as well as etiologic studies of the neural underpinnings of these behavioral outcomes. More generally, these results demonstrate the potential of neuroeconomic and behavioral economic techniques for devising objective and incentive‐compatible diagnostic tools, and investigating the etiology of psychiatric disorders.

  March 21, 2016   doi: 10.1002/da.22494   open full text
• Lethal Means Access And Assessment Among Suicidal Emergency Department Patients.
  Marian E. Betz, Matthew Miller, Catherine Barber, Brenda Beaty, Ivan Miller, Carlos A. Camargo,, Edwin D. Boudreaux.
  Depression and Anxiety. March 17, 2016
  Background Reducing access to lethal means (especially firearms) might prevent suicide, but counseling of at‐risk individuals about this strategy may not be routine. Among emergency department (ED) patients with suicidal ideation or attempts (SI/SA), we sought to describe home firearm access and examine ED provider assessment of access to lethal means. Methods This secondary analysis used data from the Emergency Department Safety Assessment and Follow‐up Evaluation, a three‐phase, eight‐center study of adult ED patients with SI/SA (2010–2013). Research staff surveyed participants about suicide‐related factors (including home firearms) and later reviewed the ED chart (including documented assessment of lethal means access). Results Among 1,358 patients with SI/SA, 11% (95% CI: 10–13%) reported ≥1 firearm at home; rates varied across sites (range: 6–26%) but not over time. On chart review, 50% (95% CI: 47–52%) of patients had documentation of lethal means access assessment. Frequency of documented assessment increased over study phases (40–60%, P < .001) but was not associated with state firearm ownership rates. Among the 337 (25%, 95% CI: 23–27%) patients discharged to home, 55% (95% CI: 49–60%) had no documentation of lethal means assessment; of these, 13% (95% CI: 8–19%; n = 24) actually had ≥1 firearm at home. Among all those reporting ≥1 home firearm to study staff, only half (50%, 95% CI: 42–59%) had provider documentation of assessment of lethal means access. Conclusions Among these ED patients with SI/SA, many did not have documented assessment of home access to lethal means, including patients who were discharged home and had ≥1 firearm at home.

  March 17, 2016   doi: 10.1002/da.22486   open full text
• Trauma Exposure And Risk Of Suicidal Ideation Among Ethnically Diverse Adults.
  Matthew H. Beristianos, Shira Maguen, Thomas C. Neylan, Amy L. Byers.
  Depression and Anxiety. March 17, 2016
  Background Little is known about the association between trauma exposure and suicidal ideation across racial/ethnic groups. Our study aim was to determine the association between trauma exposure and suicidal ideation in a nationally representative ethnically diverse sample of adults. Methods This study included 14,866 White, Hispanic, Black, and Asian participants 18 years and older involved in the Collaborate Psychiatric Epidemiology Surveys (2001–2003), comprised of three nationally representative studies (NCS‐R, NSAL, and NLAAS). Lifetime history of suicidal ideation as assessed in the World Health Organization's World Mental Health Survey Initiative version of the Composite International Diagnostic Interview (WMH‐CIDI). Results Of the 81% respondents who reported being exposed to trauma as assessed in the WMH‐CIDI, 12.1% endorsed lifetime suicidal ideation. Additionally, of the 19% who did not report trauma, 1.1% endorsed lifetime suicidal ideation. Fully adjusted, multivariable logistic regression models revealed two traumas consistently associated with significantly higher odds for suicidal ideation across all four racial groups examined: Assaultive/interpersonal violence and child maltreatment. Asians, in particular, had the highest likelihood for suicidal ideation in both trauma categories, with a near threefold increased odds for assaultive/interpersonal violence exposure (OR: 2.56; 95% CI: 1.71–3.83) and nearly ninefold increased odds for child maltreatment exposure (OR: 8.43; 95% CI: 4.91–14.49). Discussion : Suicidal ideation in racially/ethnically diverse American adults is strongly associated with assaultive/interpersonal violence and child maltreatment, independent of PTSD, MDD, and substance use. These findings highlight the need for monitoring of suicidal behavior following assaultive/interpersonal trauma and child maltreatment, regardless of the presence of a psychiatric disorder.

  March 17, 2016   doi: 10.1002/da.22485   open full text
• Impact Of Specific Phobia On The Risk Of Onset Of Mental Disorders: A 10‐Year Prospective‐Longitudinal Community Study Of Adolescents And Young Adults.
  Roselind Lieb, Marcel Miché, Andrew T. Gloster, Katja Beesdo‐Baum, Andrea H. Meyer, Hans‐Ulrich Wittchen.
  Depression and Anxiety. March 17, 2016
  Background The role of specific phobia as a potentially important psychopathological precursor condition to more severe mental disorders is understudied. We examined the prospective‐longitudinal association of early childhood/adolescent phobia with subsequent mental disorders and the proportion of outcome disease incidence attributable to specific phobia simultaneously for a broad range of disorders. Methods N = 2210 14‐ to 24‐year‐old community subjects were followed up for 10 years. DSM‐IV‐specific phobia as exposure and a broad range of DSM‐IV mental disorders as outcomes were assessed with the DSM‐IV/M‐CIDI. Logistic regressions, adjusting for confounders, were used to estimate the associations of specific phobia with the subsequent onset of outcome disorders. Results Baseline specific phobia predicted the subsequent first onset of anxiety disorders [panic disorder: risk ratio (RR) = 4.38, 95% confidence interval (2.34, 8.21); generalized anxiety disorder: RR = 4.10 (2.19, 7.69); posttraumatic stress disorder: RR = 2.15 (1.13, 4.10); obsessive–compulsive disorder: RR = 3.79 (1.63, 8.82)], affective disorders [major depression: RR = 1.54 (1.16, 2.03); bipolar disorder: RR = 2.20 (1.10, 4.41); dysthymia: RR = 2.75 (1.48, 5.11)], pain disorder: RR = 1.52 (1.14, 2.02), and eating disorders: RR = 2.27 (1.14, 4.51). Population attributable fractions (PAFs; i.e., proportion of outcome disease incidence in the total population attributable to specific phobia) were highest for panic disorder (PAF = 22.9), generalized anxiety disorder (PAF = 32.3), and obsessive–compulsive disorders (PAF = 30.2). Conclusion This study provides strong evidence that specific phobia is an early onset disorder predicting the subsequent onset of a range of disorders. Future studies should examine the underlying mechanisms and the potential of using specific phobia as a target for prevention of subsequent psychopathology.

  March 17, 2016   doi: 10.1002/da.22487   open full text
• The Role of Response Inhibition in Medicated and Unmedicated Obsessive‐Compulsive Disorder Patients: Evidence from the Stop‐Signal Task.
  Eyal Kalanthroff, Tobias Teichert, Michael G. Wheaton, Marcia B. Kimeldorf, Omer Linkovski, Susanne E. Ahmari, Abby J. Fyer, Franklin R. Schneier, Gideon E. Anholt, H. Blair Simpson.
  Depression and Anxiety. March 17, 2016
  Background Numerous studies have investigated response inhibition (RI) in obsessive‐compulsive disorder (OCD), with many reporting that OCD patients demonstrate deficits in RI as compared to controls. However, reported effect sizes tend to be modest and results have been inconsistent, with some studies finding intact RI in OCD. To date, no study has examined the effect of medications on RI in OCD patients. Methods We analyzed results from a stop‐signal task to probe RI in 65 OCD patients (32 of whom were medicated) and 58 healthy controls (HCs). Results There was no statistically significant difference in stop‐signal reaction time between the OCD group and the HC group, or between the medicated and unmedicated OCD patients. However, variability was significantly greater in the medicated OCD group compared to the unmedicated group. Conclusions These results indicate that some samples of OCD patients do not have deficits in RI, making it unlikely that deficient RI underlies repetitive behaviors in all OCD patients. Future research is needed to fully elucidate the impact of medication use on stop‐signal performance. Implications for future research on the cognitive processes underlying repetitive thoughts and behaviors are discussed.

  March 17, 2016   doi: 10.1002/da.22492   open full text
• Suicidal Depressed Patients Respond Less Well To Antidepressants In The Short Term.
  Jorge Lopez‐Castroman, Isabelle Jaussent, Philip Gorwood, Philippe Courtet.
  Depression and Anxiety. February 16, 2016
  Background Suicidal thoughts and behaviors could be associated to a poor response to antidepressant treatment, but the exclusion of suicidal patients from randomized clinical trials restricts the available knowledge. In this study, we aimed at defining more precisely the response to antidepressants among suicidal patients and the threshold of suicidality that best predicts a poor response. Method We investigated the short‐term response to a new antidepressant treatment of 4,041 depressed outpatients depending on their suicidal status (passive or active suicidal ideation (SI), history of suicide attempts [SAs]), either self‐rated or clinician‐rated. Depression outcomes, measured with the Hospital Anxiety and Depression Scale, and remission rates were compared depending on suicidal status at baseline using logistic regression models. Results Using either a qualitative or a quantitative approach to measure SI, we found that suicidal patients were less likely to improve or attain remission, but not more likely to worsen, than nonsuicidal patients. In the multivariate analyses, SI (odds ratio [OR] = 1.40; 95% confidence interval [CI]: 1.18–1.65) and a history of SA (OR = 1.39; 95% CI: 1.16–1.66) were the best predictors of nonremission, independently of the class of antidepressant treatment. Conclusion Antidepressant treatment seems to be less effective among those patients that need it most. Clinical trials including suicidal patients are needed to investigate specific treatment options.

  February 16, 2016   doi: 10.1002/da.22473   open full text
• Effectiveness Of Dialectical Behavior Therapy Versus Collaborative Assessment And Management Of Suicidality Treatment For Reduction Of Self‐Harm In Adults With Borderline Personality Traits And Disorder—A Randomized Observer‐Blinded Clinical Trial.
  Kate Andreasson, Jesper Krogh, Christina Wenneberg, Helle K. L. Jessen, Kristine Krakauer, Christian Gluud, Rasmus R. Thomsen, Lasse Randers, Merete Nordentoft.
  Depression and Anxiety. February 08, 2016
  Background Many psychological treatments have shown effect on reducing self‐harm in adults with borderline personality disorder. There is a need of brief psychotherapeutical treatment alternative for suicide prevention in specialized outpatient clinics. Methods/Design The DiaS trial was designed as a pragmatic single‐center, two‐armed, parallel‐group observer‐blinded, randomized clinical superiority trial. The participants had at least two criteria from the borderline personality disorder diagnosis and a recent suicide attempt (within a month). The participants were offered 16 weeks of dialectical behavior therapy (DBT) versus up to 16 weeks of collaborative assessment and management of suicidality (CAMS) treatment. The primary composite outcome was the number of participants with a new self‐harm (nonsuicidal self‐injury [NSSI] or suicide attempt) at week 28 from baseline. Other exploratory outcomes were: severity of borderline symptoms, depressive symptoms, hopelessness, suicide ideation, and self‐esteem. Results At 28 weeks, the number of participants with new self‐harm in the DBT group was 21 of 57 (36.8%) versus 12 of 51 (23.5%) in the CAMS treatment (OR: 1.90; 95% CI: 0.80–4.40; P = .14). When assessing the effect of DBT versus CAMS treatment on the individual components of the primary outcome, we observed no significant differences in the number of NSSI (OR: 1.60; 95% CI: 0.70–3.90; P = .31) or number of attempted suicides (OR: 2.24; 95% CI: 0.80–7.50; P = .12). Conclusion In adults with borderline personality traits and disorder and a recent suicide attempt, DBT does not seem superior compared with CAMS for reduction of number of self‐harm or suicide attempts. However, further randomized clinical trials may be needed.

  February 08, 2016   doi: 10.1002/da.22472   open full text
• Specific Mood Symptoms Confer Risk For Subsequent Suicidal Ideation In Bipolar Disorder With And Without Suicide Attempt History: Multi‐Wave Data From Step‐Bd.
  Jonathan P. Stange, Evan M. Kleiman, Louisa G. Sylvia, Pedro Vieira da Silva Magalhães, Michael Berk, Andrew A. Nierenberg, Thilo Deckersbach.
  Depression and Anxiety. January 12, 2016
  Background Little is known about specific mood symptoms that may confer risk for suicidal ideation (SI) among patients with bipolar disorder (BD). We evaluated prospectively whether particular symptoms of depression and mania precede the onset or worsening of SI, among adults with or without a history of a suicide attempt. Methods We examined prospective data from a large (N = 2,741) cohort of patients participating in the Systematic Treatment Enhancement Program for BD (STEP‐BD). We evaluated history of suicide attempts at baseline, and symptoms of depression and mania at baseline and follow‐up visits. Hierarchical linear modeling tested whether specific mood symptoms predicted subsequent levels of SI, and whether the strength of the associations differed based on suicide attempt history, after accounting for the influence of other mood symptoms and current SI. Results Beyond overall current depression and mania symptom severity, baseline SI, and illness characteristics, several mood symptoms, including guilt, reduced self‐esteem, psychomotor retardation and agitation, increases in appetite, and distractibility predicted more severe levels of subsequent SI. Problems with concentration, distraction, sleep loss and decreased need for sleep predicted subsequent SI more strongly among individuals with a suicide attempt history. Conclusions Several specific mood symptoms may confer risk for the onset or worsening of SI among treatment‐seeking patients with BD. Individuals with a previous suicide attempt may be at greater risk in part due to greater reactivity to certain mood symptoms in the form of SI. However, overall, effect sizes were small, suggesting the need to identify additional proximal predictors of SI.

  January 12, 2016   doi: 10.1002/da.22464   open full text
• Ptsd Symptoms Across Pregnancy And Early Postpartum Among Women With Lifetime Ptsd Diagnosis.
  Maria Muzik, Ellen W. McGinnis, Erika Bocknek, Diana Morelen, Katherine L. Rosenblum, Israel Liberzon, Julia Seng, James L. Abelson.
  Depression and Anxiety. January 06, 2016
  Background Little is known about trajectories of PTSD symptoms across the peripartum period in women with trauma histories, specifically those who met lifetime PTSD diagnoses prior to pregnancy. The present study seeks to identify factors that influence PTSD symptom load across pregnancy and early postpartum, and study its impact on postpartum adaptation. Method The current study is a secondary analysis on pregnant women with a Lifetime PTSD diagnosis (N = 319) derived from a larger community sample who were interviewed twice across pregnancy (28 and 35 weeks) and again at 6 weeks postpartum, assessing socioeconomic risks, mental health, past and ongoing trauma exposure, and adaptation to postpartum. Results Using trajectory analysis, first we examined the natural course of PTSD symptoms based on patterns across peripartum, and found four distinct trajectory groups. Second, we explored factors (demographic, historical, and gestational) that shape the PTSD symptom trajectories, and examined the impact of trajectory membership on maternal postpartum adaptation. We found that child abuse history, demographic risk, and lifetime PTSD symptom count increased pregnancy‐onset PTSD risk, whereas gestational PTSD symptom trajectory was best predicted by interim trauma and labor anxiety. Women with the greatest PTSD symptom rise during pregnancy were most likely to suffer postpartum depression and reported greatest bonding impairment with their infants at 6 weeks postpartum. Conclusions Screening for modifiable risks (interpersonal trauma exposure and labor anxiety) and /or PTSD symptom load during pregnancy appears critical to promote maternal wellbeing.

  January 06, 2016   doi: 10.1002/da.22465   open full text
• Emotional Availability In Mother–Child Interaction: The Effects Of Maternal Depression In Remission And Additional History Of Childhood Abuse.
  Dorothea Kluczniok, Katja Boedeker, Anna Fuchs, Catherine Hindi Attar, Thomas Fydrich, Daniel Fuehrer, Katja Dittrich, Corinna Reck, Sibylle Winter, Andreas Heinz, Sabine C. Herpertz, Romuald Brunner, Felix Bermpohl.
  Depression and Anxiety. December 23, 2015
  Background The association between maternal depression and adverse outcomes in children is well established. Similar links have been found for maternal childhood abuse. One proposed pathway of risk transmission is reduced maternal emotional availability. Our aim was to investigate whether sensitive parenting is impaired in mothers with depression in remission, and whether among these mothers childhood abuse has an additional impact. Methods The mother–child interaction of 188 dyads was assessed during a play situation using the Emotional Availability Scales, which measure the overall affective quality of the interaction: maternal sensitivity, structuring, nonhostility, and nonintrusiveness. Mothers with depression in remission were compared to healthy mothers. Children were between 5 and 12 years old. Group differences and impact of additional childhood abuse were analyzed by one‐factorial analyses of covariance and planned contrasts. Results Mothers with depression in remission showed less emotional availability during mother–child interaction compared to healthy control mothers. Specifically, they were less sensitive and, at trend‐level, less structuring and more hostile. Among these mothers, we found an additional effect of severe maternal childhood abuse on maternal sensitivity: Mothers with depression in remission and a history of severe childhood abuse were less sensitive than remitted mothers without childhood abuse. Conclusions Our data suggest that depression impacts on maternal emotional availability during remission, which might represent a trait characteristic of depression. Mothers with depression in remission and additional severe childhood abuse were particularly affected. These findings may contribute to the understanding of children's vulnerability to develop a depressive disorder themselves.

  December 23, 2015   doi: 10.1002/da.22462   open full text
• Evaluating Potential Iatrogenic Suicide Risk In Trauma‐Focused Group Cognitive Behavioral Therapy For The Treatment Of Ptsd In Active Duty Military Personnel.
  Craig J. Bryan, Tracy A. Clemans, Ann Marie Hernandez, Jim Mintz, Alan L. Peterson, Jeffrey S. Yarvis, Patricia A. Resick,.
  Depression and Anxiety. December 04, 2015
  Objective To determine whether group cognitive processing therapy‐cognitive only version (CPT‐C) is associated with iatrogenic suicide risk in a sample of active duty US Army personnel diagnosed with posttraumatic stress disorder (PTSD). Possible iatrogenic effects considered include the incidence and severity of suicide ideation, worsening of preexisting suicide ideation, incidence of new‐onset suicide ideation, and incidence of suicide attempts among soldiers receiving group CPT‐C. Comparison with group present‐centered therapy (PCT) was made to contextualize findings. Method One hundred eight soldiers (100 men, eight women) diagnosed with PTSD were randomized to receive either group CPT‐C or group PCT. PTSD diagnosis was confirmed via structured clinician interview. Suicide ideation, depression severity, and PTSD severity were assessed at pretreatment, weekly during treatment, and 2 weeks, 6 months, and 12 months posttreatment. Results Rates of suicide ideation significantly decreased across both treatments. Among soldiers with pretreatment suicide ideation, severity of suicide ideation significantly decreased across both treatments and was maintained for up to 12 months posttreatment. Exacerbation of preexisting suicide ideation was uncommon in both treatments. New‐onset suicide ideation was rare and similar across both treatments (<16%). There were no suicide attempts during treatment or follow‐up in either group. Change in depression symptoms predicted change in suicide risk. Conclusions Suicide‐related outcomes were similar across both treatments and primarily associated with comorbid depression. Suicide‐related outcomes in group CPT‐C were rare and comparable to patterns observed in an active, nontrauma‐focused therapy, even among soldiers who entered treatment with suicide ideation. Clinical Trials.gov Identifier NCT01286415, https://clinicaltrials.gov/ct2/show/NCT01286415.

  December 04, 2015   doi: 10.1002/da.22456   open full text
• Efficacy And Long‐Term Clinical Outcome Of Comorbid Posttraumatic Stress Disorder And Major Depressive Disorder After Electroconvulsive Therapy.
  Naser Ahmadi, Lori Moss, Edwin Simon, Charles B. Nemeroff, Nutan Atre‐Vaidya.
  Depression and Anxiety. November 10, 2015
  Background Many patients fulfill criteria for both posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Electroconvulsive therapy (ECT) is generally acknowledged to be the most‐effective treatment for refractory MDD. This study investigated the efficacy of ECT on long‐term clinical outcome of comorbid PTSD and MDD. Methods This retrospective nested matched case‐control study is inclusive of 22,164 subjects [3,485 with comorbid MDD and PTSD (92 with ECT and 3,393 without ECT) and 18,679 without MDD and PTSD]. Results Using the clinical global impression scale (CGI) to assess efficacy, more‐robust improvement of PTSD and MDD symptoms was observed with ECT (90%), compared to antidepressant‐treatment alone(50%) (P = 0.001). During the median of 8 years of follow‐up, the death‐rate was 8% in subjects without PTSD and MDD, 9.7% in PTSD and MDD treated with ECT and 18% in PTSD and MDD without ECT (P < 0.05). The suicide‐rate was 2.2 and 5.9% in PTSD and MDD with and without ECT‐treatment, respectively (P < 0.05). Survival‐analyses revealed that the relative‐risk of cardiovascular and all‐cause mortality is not significantly different in patients with comorbid MDD and PTSD treated with ECT, compared to a matched‐cohort without PTSD and MDD (P > 0.05). The relative risk of suicidality, all‐cause, and cardiovascular mortality was reduced 64, 65, and 46% in MDD and PTSD patients treated with ECT, compared to those without ECT (P < 0.05). Conclusion ECT is associated with a significant reduction of symptoms of PTSD and MDD, as well as reduction in risk of suicidality, cardiovascular, and all‐cause mortality in MDD and PTSD, an effect more robust than antidepressant‐therapy alone.

  November 10, 2015   doi: 10.1002/da.22451   open full text
• Taking The Pulse Of Prolonged Exposure Therapy: Physiological Reactivity To Trauma Imagery As An Objective Measure Of Treatment Response.
  Bethany C. Wangelin, Peter W. Tuerk.
  Depression and Anxiety. November 02, 2015
  Background Physiological reactivity to trauma‐related cues is a primary symptom of PTSD and can be assessed objectively using script‐driven imagery paradigms. However, subjective self‐reported symptom measures are the most common outcome indices utilized in PTSD treatment trials and clinic settings. We examined physiological reactivity during a short trauma imagery task as an objective index of response to PTSD treatment, optimized for use in routine clinical care settings. Methods Participants were 35 male combat veterans receiving prolonged exposure (PE) therapy in a Veterans Affairs outpatient clinic. In addition to traditional subjective self‐reported and clinician‐rated symptom measures, patients also completed a script‐driven imagery task in which heart rate (HR) and skin conductance (SC) were recorded at three assessment points across treatment. We examined changes in subjective symptom measures and objective trauma‐specific physiological reactivity over the course of PE, and investigated the association between pretreatment physiological reactivity and treatment response. Results Patients who completed PE showed significantly diminished HR and SC reactivity to trauma imagery across therapy. Additionally, individuals showing greater trauma‐specific HR reactivity at pretreatment showed greater reductions in subjectively reported PTSD symptoms after the first session of imaginal exposure, and at posttreatment. Conclusions Findings support the utility of physiological reactivity during trauma imagery as an objective outcome measure that has the potential to be incorporated into evidence‐based PTSD treatment in routine clinical settings, or prospective studies related to the individualization of care at pretreatment.

  November 02, 2015   doi: 10.1002/da.22449   open full text
• Ways Of Acquiring Flying Phobia.
  Bettina Schindler, Noortje Vriends, Jürgen Margraf, Rolf‐Dieter Stieglitz.
  Depression and Anxiety. October 20, 2015
  Background The few studies that have explored how flying phobia is acquired have produced contradictory results. We hypothesized that classical conditioning plays a role in acquiring flying phobia and investigated if vicarious (model) learning, informational learning through media, and experiencing stressful life events at the time of onset of phobia also play a role. Method Thirty patients with flying phobia and thirty healthy controls matched on age, sex, and education were interviewed with the Mini‐DIPS, the short German version of the Anxiety Disorders Interview Schedule (DSM‐IV diagnostic criteria) and the Fear‐of‐Flying History Interview. Results Fifty Percent of patients with flying phobia and 53% of healthy controls reported frightening events in the air. There was no significant difference between the two samples. Thus there were not more classical conditioning events for patients with flying phobia. There also was no significant difference between the two samples for vicarious (model) learning: 37% of flying phobia patients and 23% of healthy controls felt influenced by model learning. The influence of informational learning through media was significantly higher for the clinical sample (70%) than for the control group (37%). Patients with flying phobia experienced significantly more stressful life events in the period of their frightening flight experience (60%) than healthy controls (19%). Conclusions Frightening experiences while flying are quite common, but not everybody develops a flying phobia. Stressful life events and other factors might enhance conditionability. Informational learning through negative media reports probably reinforces the development of flying phobia. Clinical implications are discussed.

  October 20, 2015   doi: 10.1002/da.22447   open full text
• A Comprehensive Examination Of White Matter Tracts And Connectometry In Major Depressive Disorder.
  Doreen M. Olvet, Lauren Delaparte, Fang‐Cheng Yeh, Christine DeLorenzo, Patrick J. McGrath, Myrna M. Weissman, Phillip Adams, Maurizio Fava, Thilo Deckersbach, Melvin G. McInnis, Thomas J. Carmody, Crystal M. Cooper, Benji T. Kurian, Hanzhang Lu, Marisa S. Toups, Madhukar H. Trivedi, Ramin V. Parsey.
  Depression and Anxiety. October 19, 2015
  Background Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI). Methods 139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract‐based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD. Results There were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry. Conclusions The lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts.

  October 19, 2015   doi: 10.1002/da.22445   open full text
• Stressors, Symptom Profile, And Predictors Of Adjustment Disorder In Cancer Patients. Results From An Epidemiological Study With The Composite International Diagnostic Interview, Adaptation For Oncology (Cidi‐O).
  Bianca Hund, Katrin Reuter, Martin Härter, Elmar Brähler, Hermann Faller, Monika Keller, Holger Schulz, Karl Wegscheider, Joachim Weis, Hans‐Ulrich Wittchen, Uwe Koch, Michael Friedrich, Anja Mehnert.
  Depression and Anxiety. October 16, 2015
  Background We aimed to investigate type and frequency of stressors, predominant symptom profiles, and predictors of adjustment disorders (AD) in cancer patients across major tumor entities. Methods In this epidemiological study, we examined 2,141 cancer patients out of 4,020 screened with the Composite International Diagnostic Interview, adaptation for oncology (CIDI‐O). AD were operationalized as subthreshold disorders according to DSM‐IV criteria. Results In our sample, 265 out of 2,141 patients (12.4%) met all criteria for AD (unweighted 4‐week prevalence). The disclosure of the cancer diagnosis, relapse or metastases, and cancer treatments were most frequently described as stressors associated with depressive or anxious symptoms. With regard to AD symptom profiles, patients showed high prevalence rates of affective symptoms according to the DSM‐IV criteria of Major Depression: The highest prevalence rates were found for cognitive disturbances (concentration and memory problems) (88%), sleeping disturbances (86%), and depressive mood (83%). We found sex, education, and metastasis as significant predictors for AD. Higher education was the most influential predictor. Men were half as likely to report symptoms fulfilling the AD criteria as women. Patients with metastasized tumors had a more than 80% higher risk of AD than those without metastasis. However, the explained variance of our model is very small (Nagelkerke's R² = 0.08). Conclusions Patients with AD can be identified using a standardized instrument and deserve clinical attention, as they often show severe clinical symptoms and impairments. Improving the clinical conceptualization of AD by the adding‐on of potential stress‐response‐symptoms is necessary to identify severe psychological strain.

  October 16, 2015   doi: 10.1002/da.22441   open full text
• Patterns Of Clinically Significant Cognitive Impairment In Hoarding Disorder.
  R. Scott Mackin, Ofilio Vigil, Philip Insel, Alana Kivowitz, Eve Kupferman, Christina Hough, Shiva Fekri, Ross Crothers, David Bickford, Kevin L. Delucchi, Carol A. Mathews.
  Depression and Anxiety. October 16, 2015
  Objectives The cognitive characteristics of individuals with hoarding disorder (HD) are not well understood. Existing studies are relatively few and somewhat inconsistent but suggest that individuals with HD may have specific dysfunction in the cognitive domains of categorization, speed of information processing, and decision making. However, there have been no studies evaluating the degree to which cognitive dysfunction in these domains reflects clinically significant cognitive impairment (CI). Methods Participants included 78 individuals who met DSM‐V criteria for HD and 70 age‐ and education‐matched controls. Cognitive performance on measures of memory, attention, information processing speed, abstract reasoning, visuospatial processing, decision making, and categorization ability was evaluated for each participant. Rates of clinical impairment for each measure were compared, as were age‐ and education‐corrected raw scores for each cognitive test. Results HD participants showed greater incidence of CI on measures of visual memory, visual detection, and visual categorization relative to controls. Raw‐score comparisons between groups showed similar results with HD participants showing lower raw‐score performance on each of these measures. In addition, in raw‐score comparisons HD participants also demonstrated relative strengths compared to control participants on measures of verbal and visual abstract reasoning. Conclusions These results suggest that HD is associated with a pattern of clinically significant CI in some visually mediated neurocognitive processes including visual memory, visual detection, and visual categorization. Additionally, these results suggest HD individuals may also exhibit relative strengths, perhaps compensatory, in abstract reasoning in both verbal and visual domains.

  October 16, 2015   doi: 10.1002/da.22439   open full text
• Symptom And Functional Traits Of Brief Major Depressive Episodes And Discrimination Of Bereavement.
  Patrick J. McCabe, Paul P. Christopher.
  Depression and Anxiety. October 16, 2015
  Background Despite the removal of the bereavement exclusion from DSM‐5, clinicians may feel uncertain on how to proceed when caring for a patient who presents with depressive symptoms following the death of someone close. The ability to better distinguish, on a symptom and functional level, between patients who experience depression in the context of bereavement and those with nonbereavement‐related depression, could help guide clinical decision making. Method Individual and clustered depressive symptom and impairment measures were used for modeling bereavement status within a nationally representative longitudinal cohort. Deviance, linear shrinkage factor, and bias‐corrected c‐statistic were used for identifying a well‐calibrated and discriminating final model. Results Of the 450 (1.2%) respondents with a single brief major depressive episode, 162 (38.4%) reported the episode as bereavement‐related. The bereaved were less likely to endorse worthlessness (P < .001), social conflict (P < .001), distress (P < .001), thoughts of suicide (P = .001), wanting to die (P = .01), self‐medicating (P = .01), and being withdrawn (P = .04). In a multivariate model, the bereaved were more likely to have thoughts of their own death (P = .003), guilt coupled with weight or appetite loss (P = .013), and were less likely to report social conflict (P < .001), worthlessness coupled with difficulty making decisions (P < .001), thoughts of suicide (P = .006), distress coupled with weight or appetite gain (P = .022), and self‐medicating (P = .045). Conclusions Traits and trait combinations differentiate individuals who experience brief depressive episodes following the death of a loved one from other brief episodes. These differences can help guide clinical care of patients who present with depressive symptoms shortly after a loved one's death.

  October 16, 2015   doi: 10.1002/da.22446   open full text
• Group‐Based Symptom Trajectories In Indicated Prevention Of Adolescent Depression.
  Frédéric N. Brière, Paul Rohde, Eric Stice, Julien Morizot.
  Depression and Anxiety. October 12, 2015
  Background Adolescent depression prevention research has focused on mean intervention outcomes, but has not considered heterogeneity in symptom course. Here, we empirically identify subgroups with distinct trajectories of depressive symptom change among adolescents enrolled in two indicated depression prevention trials and examine how cognitive‐behavioral (CB) interventions and baseline predictors relate to trajectory membership. Methods Six hundred thirty‐one participants were assigned to one of three conditions: CB group intervention, CB bibliotherapy, and brochure control. We used group‐based trajectory modeling to identify trajectories of depressive symptoms from pretest to 2‐year follow‐up. We examined associations between class membership and conditions using chi‐square tests and baseline predictors using multinomial regressions. Results We identified four trajectories in the full sample. Qualitatively similar trajectories were found in each condition separately. Two trajectories of positive symptom course (low‐declining, high‐declining) had declining symptoms and were distinguished by baseline symptom severity. Two trajectories of negative course (high‐persistent, resurging), respectively, showed no decline in symptoms or decline followed by symptom reappearance. Participants in the brochure control condition were significantly more likely to populate the high‐persistent trajectory relative to either CB condition and were significantly less likely to populate the low‐declining trajectory relative to CB group. Several baseline factors predicted trajectory classes, but gender was the most informative prognostic factor, with males having increased odds of membership in a high‐persistent trajectory relative to other trajectories. Conclusions Findings suggest that CB preventive interventions do not alter the nature of trajectories, but reduce the risk that adolescents follow a trajectory of chronically elevated symptoms.

  October 12, 2015   doi: 10.1002/da.22440   open full text
• Hpa Axis Related Genes And Response To Psychological Therapies: Genetics And Epigenetics.
  Susanna Roberts, Robert Keers, Kathryn J Lester, Jonathan R. I. Coleman, Gerome Breen, Kristian Arendt, Judith Blatter‐Meunier, Peter Cooper, Cathy Creswell, Krister Fjermestad, Odd E. Havik, Chantal Herren, Sanne M. Hogendoorn, Jennifer L. Hudson, Karen Krause, Heidi J. Lyneham, Talia Morris, Maaike Nauta, Ronald M. Rapee, Yasmin Rey, Silvia Schneider, Sophie C. Schneider, Wendy K. Silverman, Mikael Thastum, Kerstin Thirlwall, Polly Waite, Thalia C. Eley, Chloe C. Y. Wong.
  Depression and Anxiety. October 07, 2015
  Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress‐related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele‐specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype‐dependent manner.

  October 07, 2015   doi: 10.1002/da.22430   open full text
• Exploring Personality Diagnosis Stability Following Acute Psychotherapy For Chronic Posttraumatic Stress Disorder.
  John C. Markowitz, Eva Petkova, Tatyana Biyanova, Ke Ding, Eun Jung Suh, Yuval Neria.
  Depression and Anxiety. October 06, 2015
  Background Axis I comorbidity complicates diagnosing axis II personality disorders (PDs). PDs might influence Axis I outcome. No research has examined psychotherapy effects on PDs of treating Axis I comorbidity. Secondary analysis of a randomized controlled trial examined PD diagnostic stability after brief psychotherapy of chronic posttraumatic stress disorder (PTSD). Methods Patients with chronic PTSD were randomly assigned to 14 weeks of prolonged exposure, interpersonal psychotherapy, or relaxation therapy. Assessments included the Structured Clinical Interview for DSM‐IV, Patient Version (SCID‐P) and Structured Clinical Interview for DSM‐IV Axis II Disorders (SCID‐II) at baseline, week 14, and for treatment responders (≥30% clinician‐administered PTSD scale improvement, defined a priori) at week 26 follow‐up. We hypothesized patients whose PTSD improved would retain fewer baseline PD diagnoses posttreatment, particularly with personality traits PTSD mimics, e.g. paranoid and avoidant. Results Forty‐seven (47%) of 99 SCID‐II patients evaluated at baseline received a SCID‐II diagnosis: paranoid (28%), obsessive–compulsive (27%), and avoidant (23%) PDs were most prevalent. Among 78 patients who repeated SCID‐II evaluations posttreatment, 45% (N = 35) had baseline PD diagnoses, of which 43% (N = 15/35) lost at week 14. Three (7%) patients without baseline PDs acquired diagnoses at week 14; 10 others shifted diagnoses. Treatment modality and PTSD response were unrelated to PD improvement. Of treatment responders reevaluated at follow‐up (N = 44), 56% with any baseline Axis II diagnosis had none at week 26. Conclusion This first evaluation of Axis I psychotherapy effects on personality disorder stability found that acutely treating a chronic state decreased apparent trait—across most PDs observed. These exploratory findings suggest personality diagnoses may have limited prognostic meaning in treating chronic PTSD.

  October 06, 2015   doi: 10.1002/da.22436   open full text
• Influence Of Study Design On Treatment Response In Anxiety Disorder Clinical Trials.
  Bret R Rutherford, Veronika S. Bailey, Franklin R. Schneier, Emily Pott, Patrick J. Brown, Steven P. Roose.
  Depression and Anxiety. October 05, 2015
  Objective The influence of study design variables and publication year on response to medication and placebo was investigated in clinical trials for social anxiety disorder (SAD), generalized anxiety disorder (GAD), and panic disorder (PD). Method Hierarchical linear modeling determined whether publication year, treatment assignment (medication vs. placebo), study type (placebo‐controlled or active comparator), study duration, and the number of study visits affected the mean change associated with medication and placebo. Results In the 66 trials examined, the change associated with both medication and placebo increased over time (t = 4.23, df = 39, P < .001), but average drug–placebo differences decreased over time (t = −2.04, df = 46, P = .047). More severe baseline illness was associated with greater drug–placebo differences for serotonin norepinephrine reuptake inhibitors (SNRIs, t = 3.46, df = 106, P = .001) and selective serotonin reuptake inhibitors (SSRI, t = 10.37, df = 106, P < .001). Improvement with medication was significantly greater in active‐comparator studies compared to placebo‐controlled trials (t = 3.41, df = 39, P = .002). A greater number of study visits was associated with greater symptom improvement in PD trials relative to SAD (t = 2.83, df = 39, P = .008) and GAD (t = 2.16, df = 39, P = .037). Conclusions Placebo response is substantial in SAD, GAD, and PD trials, and its rise over time has been associated with diminished drug–placebo differences. Study design features that influence treatment response in anxiety disorder trials include patient expectancy, frequency of follow‐up visits, and baseline illness severity.

  October 05, 2015   doi: 10.1002/da.22433   open full text
• Anxious And Aggressive: The Co‐Occurrence Of Ied With Anxiety Disorders.
  Katherine M. Keyes, Katie A. McLaughlin, Thomas Vo, Todd Galbraith, Richard G. Heimberg.
  Depression and Anxiety. September 30, 2015
  Background Evidence suggests that impulsive aggression and explosive anger are common among individuals with anxiety disorders; yet, the influence of intermittent explosive disorder (IED) on the onset, course, consequences, and patterns of comorbidity among those with anxiety disorders is unknown. Methods Data were drawn from the National Comorbidity Survey Replication (N = 9,282) and Adolescent Supplement (N = 9,632), nationally representative surveys conducted between 2001 and 2004. Diagnoses were based on structured lay‐administered interviews. Lifetime diagnoses were assessed with structured instruments. Outcomes included comorbidity, functional and role impairment, and treatment utilization. Results Adolescents with a lifetime anxiety disorder had a higher prevalence of a lifetime anger attacks (68.5%) and IED (22.9%) than adolescents without a lifetime anxiety disorder (48.6 and 7.8%, respectively), especially social phobia and panic disorders. Similar elevation was found for adults. Age of onset and course of anxiety disorders did not differ by IED. Severe functional impairment associated with anxiety was higher among adolescents (39.3%) and adults (45.7%) with IED than those without IED (29.2 and 28.2%, respectively). Comorbidity for all other disorders was elevated. However, individuals with anxiety disorders and IED were no more likely to use treatment services than those with anxiety disorders without IED. Conclusions Individuals with IED concomitant to anxiety disorder, especially social phobia and panic, are at marked risk for worse functional impairment and a higher burden of comorbidity, but onset and course of anxiety disorder do not differ, and those with anxiety and IED are no more likely to utilize treatment services. Assessment, identification, and specialized treatment of anger in the context of anxiety disorders are critical to reducing burden.

  September 30, 2015   doi: 10.1002/da.22428   open full text
• Classification Of Anxiety Disorders Comorbid With Major Depression: Common Or Distinct Influences On Risk?
  Arden Moscati, Jonathan Flint, Kenneth S. Kendler.
  Depression and Anxiety. September 29, 2015
  Background Anxiety and depression display frequent comorbidity. Individuals with comorbid disorders also often have more extreme symptomatology than those with single disorders. This correlation between comorbidity and severity poses an interesting question: Are comorbid forms of anxiety and depression essentially just more severe versions of the pure disorders? Methods In a large major depression (MD) case–control sample of individuals from the China, Oxford and VCU Experimental Research on Genetic Epidemiology project, we examined the patterns of lifetime anxiety comorbidity (including generalized anxiety disorder—GAD, panic disorder, and five phobia subtypes) among MD cases (N = 5,864) in this population. Binary and multinomial logistic regression was used to estimate associations between risk factors and outcomes including MD as well as latent class membership, which were compared using continuation ratios. Results We found a five‐class solution to fit best, and each resulting class had a distinct pattern of association with the tested risk factors. The use of continuation ratios suggests that a class characterized by high endorsement of GAD is comparable to a more severely affected “pure MD” group. The other three classes (characterized by agoraphobia, various specific phobias, and by high endorsement of all comorbid anxiety disorders, respectively) appear to differ meaningfully from MD alone. Conclusions Risk for MD resulting from environmental and psychosocial factors may also predispose individuals to GAD, and less consistently, other anxiety disorders. Presentations of MD with certain phobias display distinguishably different patterns of risk, however, and are therefore likely qualitatively distinct.

  September 29, 2015   doi: 10.1002/da.22432   open full text
• Childhood Maltreatment And The Course Of Depressive And Anxiety Disorders: The Contribution Of Personality Characteristics.
  Jacqueline G. F. M. Hovens, Erik J. Giltay, Albert M. Hemert, Brenda W. J. H. Penninx.
  Depression and Anxiety. September 29, 2015
  Background We investigated the effect of childhood maltreatment on predicting the 4‐year course of depressive and anxiety disorders and the possible mediating role of personality characteristics in the association between childhood maltreatment and illness course. Methods Longitudinal data in a large sample of participants with baseline depressive and/or anxiety disorders (n = 1,474, 18–65 years) were collected in the Netherlands Study of Depression and Anxiety. At baseline, childhood maltreatment was assessed with a semistructured interview. Personality trait questionnaires (Neuroticism–Extroversion–Openness Five Factor Inventory, Mastery scale, and Leiden Index of Depression Sensitivity), recent stressful life events (List of Threatening Experiences Questionnaire), and psychosocial variables were administered. The Life Chart Interview was used to determine the time to remission of depressive and/or anxiety disorders. Results At baseline, 846 participants (57.4%) reported any childhood maltreatment. Childhood maltreatment had a negative impact on psychosocial functioning and was predictive of more unfavorable personality characteristics and cognitive reactivity styles (P < 0.001). Childhood maltreatment was a significant predictor of lower likelihood of remission of depressive and/or anxiety disorders (HR = 0.94, P < 0.001). High levels of neuroticism, hopelessness, external locus of control, and low levels of extraversion were mediating the relationship between childhood maltreatment and 4‐year remission of depressive and anxiety disorders. Conclusions Certain personality characteristics are key players in the mechanism linking childhood maltreatment to an adverse illness course of depressive and anxiety disorders. Early interventions—reducing neuroticism and hopelessness, and enhancing extraversion and locus of control—might contribute to a better prognosis in a “high‐risk” group of depressive and anxiety disorders.

  September 29, 2015   doi: 10.1002/da.22429   open full text
• Cohort Effects Of Suicide Mortality Are Sex Specific In The Rapidly Developed Hong Kong Chinese Population, 1976–2010.
  Roger Y. Chung, Benjamin H. K. Yip, Sandra S. M. Chan, Samuel Y. S. Wong.
  Depression and Anxiety. September 28, 2015
  Background To examine temporal variations of age, period, and cohort on suicide mortality rate in Hong Kong (HK) from 1976 to 2010, and speculate the macroenvironmental mechanisms of the observed trends. Methods Poisson age‐period‐cohort modeling was used to delineate the effects of age, period, and cohort on suicide mortality. Analysis by sex was also conducted to examine if gender difference exists for suicidal behaviours. Results Age‐cohort model provides the best fit to the mortality data, implying that the cohort effect is likely to explain more of the contributions to HK's suicide mortality pattern than the period effect. Risk of suicide mortality increases nonlinearly with age and accelerates after age 65–69 for both sexes. Moreover, the cohort effects differ between the sexes—risk of mortality increases continually for men born after 1961, but no change is observed for women since the 1941 cohort. Conclusions With increased risk of suicide mortality in younger cohorts and the age effect of suicide mortality, we may see future increase in suicide mortality as these younger cohorts age. Further studies are needed to clarify plausible associations between broader sociohistorical changes in the population impacting psychological risk factors and suicidal behaviour to better inform suicide prevention strategies.

  September 28, 2015   doi: 10.1002/da.22431   open full text
• Sleep And Treatment Outcome In Posttraumatic Stress Disorder: Results From An Effectiveness Study.
  Miriam J. J. Lommen, Nick Grey, David M. Clark, Jennifer Wild, Richard Stott, Anke Ehlers.
  Depression and Anxiety. September 22, 2015
  Background Most patients with posttraumatic stress disorder (PTSD) suffer from sleep problems. Concerns have been raised about possible detrimental effects of sleep problems on the efficacy of psychological treatments for PTSD. In this study, we investigated the relation of session‐to‐session changes in PTSD symptoms and sleep, and tested whether sleep problems predicted poorer short‐ and long‐term treatment outcome. Methods Self‐reported sleep quality, sleep duration, and PTSD symptoms were assessed weekly in a consecutive sample of 246 patients who received cognitive therapy for PTSD (CT‐PTSD; Ehlers & Clark, 2000), and at follow‐up (mean = 247 days posttreatment). Additionally, moderating effects of medication use and comorbid depression were assessed. Results Sleep and PTSD symptoms improved in parallel. The relation was moderated by depression: Sleep problems at the start of therapy did not predict improvement in PTSD symptoms during treatment for patients without comorbid depression. Patients with comorbid depression, however, showed less rapid decreases in PTSD symptoms, but comparable overall outcome, if their sleep quality was poor. Residual sleep problems at the end of treatment did not predict PTSD symptoms at follow‐up once residual PTSD symptoms were taken into account. Conclusions CT‐PTSD leads to simultaneous improvement in sleep and PTSD symptoms. Sleep problems may reduce the speed of recovery in PTSD patients with comorbid depression. For these patients, additional treatment sessions are indicated to achieve comparable outcomes, and additional interventions targeting sleep may be beneficial. For those without comorbid depression, self‐reported sleep problems did not interfere with response to trauma‐focused psychological treatment.

  September 22, 2015   doi: 10.1002/da.22420   open full text
• Substance Use And Suicidality: Specificity Of Substance Use By Injection To Suicide Attempts In A Nationally Representative Sample Of Adults With Major Depression.
  Shayna M. Cheek, Bridget A. Nestor, Richard T. Liu.
  Depression and Anxiety. September 22, 2015
  Background Although several risk factors for suicidal ideation (SI) have been identified in the research literature, there is a pressing need for studies evaluating markers of risk differentiating ideators from people who have attempted. According to the interpersonal theory of suicide, habituation to painful or provocative experiences increases one's acquired capability for suicide, a necessary component for the transition from SI to attempts. This theory further posits that the acquired capability for suicide should be unrelated to risk for SI. This study tested this theory by examining injection drug use, relative to less painful means of drug use, in relation to SI, suicide plans, and suicide attempts. Methods Data were drawn from the National Survey on Drug Use and Health (NSDUH), a nationally representative survey conducted annually. Participants included 10,203 adults with a history of injectable drug use and major depression. Results Injection drug use was positively associated with suicide attempts (Odds Ratio [OR] = 1.66, 95% confidence interval [CI] = 1.18–2.34), but not SI or suicide plans in the full sample. Injection drug use was also associated with suicide attempts (OR = 1.64, 95% CI = 1.14–2.35), but not plans, among ideators. Lastly, injection drug use was associated with the suicide attempts among suicide planners (OR = 1.76, 95% CI = 1.01–3.06). All analyses included sex, age, race/ethnicity, family income, substance use disorder symptom severity for injectable drugs, and depressive symptom severity as covariates. Conclusions Consistent with the interpersonal theory of suicide, injection drug use was associated with specific risk for suicide attempts but not SI or suicide plans.

  September 22, 2015   doi: 10.1002/da.22407   open full text
• Changes In Regional Brain Activation Related To Depressive State: A 2‐Year Longitudinal Functional Mri Study.
  Esther M. Opmeer, Rudie Kortekaas, Marie‐José Tol, Remco J. Renken, Liliana R. Demenescu, Saskia Woudstra, Gert J. Ter Horst, Mark A. Buchem, Nic J. A. der Wee, Dick J. Veltman, André Aleman.
  Depression and Anxiety. September 17, 2015
  Background Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology. Methods A 2‐year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning. Results Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed. Conclusions Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2‐year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states.

  September 17, 2015   doi: 10.1002/da.22425   open full text
• Effects Of Homework Compliance On Cognitive‐Behavioral Therapy With D‐Cycloserine Augmentation For Children With Obsessive Compulsive Disorder.
  Bunmi O. Olatunji, David Rosenfield, Benedetta Monzani, Georgina Krebs, Isobel Heyman, Cynthia Turner, Kayoko Isomura, David Mataix‐Cols.
  Depression and Anxiety. September 15, 2015
  Background The present study examined the effects of homework compliance on outcome from cognitive behavioral therapy (CBT) for children with obsessive‐compulsive disorder (OCD) and the extent to which these effects differ as a function of augmentation of CBT with D‐cycloserine (DCS). Methods Twenty‐seven youth with OCD were randomized to either 50 mg DCS or placebo (PBO) administered immediately after each of 10 CBT sessions, primarily consisting of exposure and ritual prevention (ERP). Independent evaluators assessed OCD severity using the Children's Yale–Brown Obsessive–Compulsive Scale (CY‐BOCS) at the start of each session. Compliance with between‐session ERP assignments was also assessed at the start of each session using the Patient ERP Adherence Scale (PEAS). Results Greater homework compliance between the previous session and the current session was related to lower CY‐BOCS at the current session. However, the relation between homework compliance and CY‐BOCS varied by treatment condition. Higher homework compliance was related to lower CY‐BOCS for participants in the DCS condition, but not for participants in the PBO condition. Furthermore, participants receiving DCS were estimated to have significantly lower CY‐BOCS than those given PBO among those with the highest levels of homework compliance. Conclusions DCS may more effectively facilitate the effects of CBT for youth with OCD when patients are compliant with prescribed homework. Theoretical and clinical implications are discussed.

  September 15, 2015   doi: 10.1002/da.22423   open full text
• Deficits In Disengaging Attention From Threat Predict Improved Response To Cognitive Behavioral Therapy For Anxiety.
  Tom J. Barry, Amy R. Sewart, Joanna J. Arch, Michelle G. Craske.
  Depression and Anxiety. September 15, 2015
  Background Pretreatment biases in attending toward threat have been shown to predict greater symptom reduction following cognitive behavioral therapy (CBT) for anxiety. Findings to date do not extend to clinical severity of diagnoses and they assess treatment response immediately posttreatment and not at follow‐up. Research in this area has also not examined components of vigilance (e.g., engagement, disengagement) or whether these effects are confined to external attention and not attention to internal symptoms of anxiety. Methods In the present investigation, 96 adults with a range of anxiety disorders completed a dot probe task to assess threat‐related attention biases before and after 12 sessions of CBT. Results Pretreatment deficits in disengaging attention from external and internal threats, and not the speed of engagement with threat, predicted reductions in clinical severity of diagnoses that were maintained 2 years later. The presence of posttreatment attention biases was not associated with increased clinical severity after treatment. Conclusions Pretreatment deficits in disengaging attention from threat may promote better and more durable response to CBT for a range anxiety disorders.

  September 15, 2015   doi: 10.1002/da.22421   open full text
• A Randomized Controlled Trial In Community Mental Health Centers Of Computer‐Assisted Cognitive Behavioral Therapy Versus Treatment As Usual For Children With Anxiety.
  Eric A. Storch, Alison Salloum, Morgan A. King, Erika A. Crawford, Ross Andel, Nicole M. McBride, Adam B. Lewin.
  Depression and Anxiety. September 14, 2015
  Objective This study aims to examine the real‐world effectiveness of a computer‐assisted cognitive behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among anxious children presenting at community mental health centers. Methods One hundred children (7–13 years) with clinically significant anxiety were randomized to receive either 12 weekly computer‐assisted CBT sessions or TAU for an equivalent duration. Assessments were conducted by independent evaluators at screening/baseline, midtreatment, posttreatment, and 1‐month followup (for computer‐assisted CBT treatment responders). Results There were significant between‐group effects favoring the computer‐assisted CBT condition on primary anxiety outcomes. Thirty of 49 (61.2%) children randomized to computer‐assisted CBT responded to treatment, which was superior to TAU (6/51, 11.8%). Relative to TAU, computer‐assisted CBT was associated with greater reductions in parent‐rated child impairment and internalizing symptoms, but not child‐rated impairment and anxiety and depressive symptoms. Treatment satisfaction and therapeutic alliance in those receiving computer‐assisted CBT was high. Treatment gains in computer‐assisted CBT responders were maintained at 1‐month followup. Conclusions Within the limitations of this study, computer‐assisted CBT is an effective and feasible treatment for anxious children when used in community mental health centers by CBT‐naïve clinicians.

  September 14, 2015   doi: 10.1002/da.22399   open full text
• Chronotype Associations With Depression And Anxiety Disorders In A Large Cohort Study.
  Niki Antypa, Nicole Vogelzangs, Ybe Meesters, Robert Schoevers, Brenda W. J. H. Penninx.
  Depression and Anxiety. September 14, 2015
  Background The chronotype, being a morning or an evening type, can influence an individual's psychological health. Studies have shown a link between depressed mood and being an evening type; however, most studies have used symptom scales and not diagnostic criteria, and confounding factors such as sleep patterns and somatic health factors have often not been considered. This study aims to examine the association between chronotype and depressive (major depressive disorder (MDD), dysthymia) and anxiety (generalized anxiety disorder, panic disorder, agoraphobia, and social phobia) disorders diagnosed using clinical interviews, while taking into account relevant sociodemographic, clinical, somatic health, and sleep parameters. Methods Data from a large cohort, the Netherlands Study of Depression and Anxiety were used (n = 1,944), which included 676 currently depressed and/or anxious patients, 831 remitted patients, and 437 healthy controls. Chronotype was assessed using the Munich Chronotype Questionnaire. Results Our results showed that current depressive and/or anxiety disorders were associated with a late chronotype (β = .10, P = .004) even when adjusting for sociodemographic, somatic health, and sleep‐related factors (β = .09, P = .03). When examining each type of disorder separately, MDD only, but not dysthymia or specific anxiety disorders, was associated with the late chronotype. The late chronotype also reported significant diurnal mood variation (worse mood in the morning). Conclusions Our findings show a clear association between MDD and late chronotype (being an evening type), after controlling for a range of pertinent factors. A late chronotype is therefore associated with a current status of MDD and deserves the relevant clinical attention when considering treatments.

  September 14, 2015   doi: 10.1002/da.22422   open full text
• Methylation Of Serotonin Receptor 3 A In Adhd, Borderline Personality, And Bipolar Disorders: Link With Severity Of The Disorders And Childhood Maltreatment.
  Nader Perroud, Seblewongel Zewdie, Ludwig Stenz, Wafae Adouan, Sabine Bavamian, Paco Prada, Rosetta Nicastro, Roland Hasler, Audrey Nallet, Camille Piguet, Ariane Paoloni‐Giacobino, Jean‐Michel Aubry, Alexandre Dayer.
  Depression and Anxiety. September 09, 2015
  Background Serotonin 3A receptor (5‐HT3AR) is associated at the genetic and epigenetic levels with a variety of psychiatric disorders and interacts with early‐life stress such as childhood maltreatment. We studied the impact of childhood maltreatment on the methylation status of the 5‐HT3AR and its association with clinical severity outcomes in relation with a functional genetic polymorphism. Methods Clinical severity indexes of 346 bipolar, borderline personality, and adult attention deficit hyperactivity disorders patients were tested for association with the DNA methylation status of eight 5‐HT3AR gene CpGs. Relationship between the functional variant rs1062613 (C > T) and methylation status on severity of the disorders were also assessed. Results Childhood maltreatment was associated with higher severity of the disease (higher number of mood episodes, history of suicide attempts, hospitalization, and younger age at onset) across disorders and within each individual disorder. This effect was mediated by two 5‐HT3AR CpGs. Compared to T allele carriers, CC carriers had higher methylation status at one CpG located 1 bp upstream of this variant. Conclusions This study shows that epigenetic modification of the 5‐HT3AR is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood.

  September 09, 2015   doi: 10.1002/da.22406   open full text
• Collaborative Care For Perinatal Depression In Socioeconomically Disadvantaged Women: A Randomized Trial.
  Nancy K. Grote, Wayne J. Katon, Joan E. Russo, Mary Jane Lohr, Mary Curran, Erin Galvin, Kathy Carson.
  Depression and Anxiety. September 08, 2015
  Background Both antenatal and postpartum depression have adverse, lasting effects on maternal and child well‐being. Socioeconomically disadvantaged women are at increased risk for perinatal depression and have experienced difficulty accessing evidence‐based depression care. The authors evaluated whether “MOMCare,”a culturally relevant, collaborative care intervention, providing a choice of brief interpersonal psychotherapy and/or antidepressants, is associated with improved quality of care and depressive outcomes compared to intensive public health Maternity Support Services (MSS‐Plus). Methods A randomized multisite controlled trial with blinded outcome assessment was conducted in the Seattle‐King County Public Health System. From January 2010 to July 2012, pregnant women were recruited who met criteria for probable major depression and/or dysthymia, English‐speaking, had telephone access, and ≥18 years old. The primary outcome was depression severity at 3‐, 6‐, 12‐, 18‐month postbaseline assessments; secondary outcomes included functional improvement, PTSD severity, depression response and remission, and quality of depression care. Results All participants were on Medicaid and 27 years old on average; 58% were non‐White; 71% were unmarried; and 65% had probable PTSD. From before birth to 18 months postbaseline, MOMCare (n = 83) compared to MSS‐Plus participants (n = 85) attained significantly lower levels of depression severity (Wald's χ2 = 6.09, df = 1, P = .01) and PTSD severity (Wald's χ2 = 4.61, df = 1, P = .04), higher rates of depression remission (Wald's χ2 = 3.67, df = 1, P = .05), and had a greater likelihood of receiving ≥4 mental health visits (Wald's χ2 = 58.23, df = 1, P < .0001) and of adhering to antidepressants in the prior month (Wald's χ2 = 10.00, df = 1, P < .01). Conclusion Compared to MSS‐Plus, MOMCare showed significant improvement in quality of care, depression severity, and remission rates from before birth to 18 months postbaseline for socioeconomically disadvantaged women. Findings suggest that evidence‐based perinatal depression care can be integrated into the services of a county public health system in the United States. Clinical Trial Registration: ClinicalTrials.govNCT01045655.

  September 08, 2015   doi: 10.1002/da.22405   open full text
• Pathological Personality Traits And The Naturalistic Course Of Internalizing Disorders Among High‐Risk Young Adults.
  Christopher C. Conway, Michelle G. Craske, Richard E. Zinbarg, Susan Mineka.
  Depression and Anxiety. September 07, 2015
  Background A personality disorder diagnosis signals a negative prognosis for depressive and anxiety disorders, but the precise abnormal personality traits that determine the temporal course of internalizing psychopathology are unknown. In the present study, we examined prospective associations between abnormal personality traits and the onset and recurrence of internalizing disorders. Methods A sample of 371 young adults at high risk for internalizing problems completed the Schedule for Nonadaptive and Adaptive Personality‐Second Edition—a measure of 12 abnormal personality traits and three temperament dimensions (i.e., Negative Temperament, Positive Temperament, Disinhibition vs. Control)—and underwent annual diagnostic interviews over 4 years of follow‐up. Results In multivariate survival analyses, Negative Temperament was a robust predictor of both new onsets and recurrences of internalizing disorder. Further, the Dependency and Self‐Harm abnormal personality dimensions emerged as independent predictors of new onsets and recurrences, respectively, of internalizing disorders after statistically adjusting for variation in temperament. Conclusions Our findings suggest that abnormal personality traits and temperament dimensions have complementary effects on the trajectory of internalizing pathology during young adulthood. In assessment and treatment settings, targeting the abnormal personality and temperament dimensions with the greatest prognostic value stands to improve the early detection of enduring internalizing psychopathology.

  September 07, 2015   doi: 10.1002/da.22404   open full text
• Perceptions Of Close And Group Relationships Mediate The Relationship Between Anxiety And Depression Over A Decade Later.
  Nicholas C. Jacobson, Michelle G. Newman.
  Depression and Anxiety. August 20, 2015
  Background Previous research has demonstrated that anxiety reliably predicts later depression, but little has been uncovered about the mechanism underlying this connection. Interpersonal relationships appear to be a viable mechanism of the association as anxiety has been shown to predict later deficits in both close (e.g., “best friendships”) and group relationships (e.g., classroom peer groups), and deficits in both close and group relationships have been linked to later depressive symptoms. The current study examined close and group relationships as potential mediators between anxiety and depression 12–14 years later. Methods In a nationally representative sample of adolescents (N = 6,504), anxiety was measured at baseline, perceptions of close relationships (i.e., feeling loved) and perceptions of group relationships (i.e., feeling part of a group) were measured 6 months later, and depression levels and diagnosis were measured 12–14 years later. Results Using structural equation models, the results showed that adolescent perceptions of both close and group relationships significantly mediated the relationship between adolescent anxiety and adult levels of depression. Furthermore, perceptions of not being accepted/loved in close relationships significantly mediated the relationship between adolescent anxiety and clinical depression in adulthood. Conclusions These results suggest that a perception of not being accepted in group relationships may be a mechanism by which heightened anxiety in adolescents leads to heightened nonclinical depression in adulthood. On the other hand, adolescent perceptions of not feeling loved or accepted in close relationships may be a mechanism by which heightened anxiety in adolescence leads to clinical depression—in adulthood.

  August 20, 2015   doi: 10.1002/da.22402   open full text
• Telemedicine Versus In‐Person Delivery Of Cognitive Processing Therapy For Women With Posttraumatic Stress Disorder: A Randomized Noninferiority Trial.
  Leslie A. Morland, Margaret‐Anne Mackintosh, Craig S. Rosen, Emy Willis, Patricia Resick, Kathleen Chard, B. Christopher Frueh.
  Depression and Anxiety. August 03, 2015
  Background This study examined the effectiveness of telemedicine to provide psychotherapy to women with posttraumatic stress disorder (PTSD) who might be unable to access treatment. Objectives were to compare clinical and process outcomes of PTSD treatment delivered via videoteleconferencing (VTC) and in‐person (NP) in an ethnically diverse sample of veteran and civilian women with PTSD. Methods A randomized controlled trial of Cognitive Processing Therapy, an evidence‐based intervention for PTSD, was conducted through a noninferiority design to compare delivery modalities on difference in posttreatment PTSD symptoms. Women with PTSD, including 21 veterans and 105 civilians, were assigned to receive psychotherapy delivered via VTC or NP. Primary treatment outcomes were changes in PTSD symptoms in the completer sample. Results Improvements in PTSD symptoms in the VTC condition (n = 63) were noninferior to outcomes in the NP condition (n = 63). Clinical outcomes obtained when both conditions were pooled together (N = 126) demonstrated that PTSD symptoms declined substantially posttreatment (mean = −20.5, 95% CI −29.6 to −11.4) and gains were maintained at 3‐ (mean = −20.8, 95% CI −30.1 to −11.5) and 6‐month followup (mean = −22.0, 95% CI −33.1 to −10.9. Veterans demonstrated smaller symptom reductions posttreatment (mean = −9.4, 95% CI −22.5 to 3.7) than civilian women (mean = −22.7, 95% CI −29.9 to −15.5. Conclusions Providing psychotherapy to women with PTSD via VTC produced outcomes comparable to NP treatment. VTC can increase access to specialty mental health care for women in rural or remote areas.

  August 03, 2015   doi: 10.1002/da.22397   open full text
• Effects Of Religious Versus Standard Cognitive‐Behavioral Therapy On Optimism In Persons With Major Depression And Chronic Medical Illness.
  Harold G. Koenig, Michelle J. Pearce, Bruce Nelson, Noha Daher.
  Depression and Anxiety. July 28, 2015
  Background We compared the effectiveness of religiously integrated cognitive behavioral therapy (RCBT) versus standard CBT (SCBT) on increasing optimism in persons with major depressive disorder (MDD) and chronic medical illness. Methods Participants aged 18–85 were randomized to either RCBT (n = 65) or SCBT (n = 67) to receive ten 50‐min sessions remotely (94% by telephone) over 12 weeks. Optimism was assessed at baseline, 12 and 24 weeks by the Life Orientation Test‐Revised. Religiosity was assessed at baseline using a 29‐item scale composed of religious importance, individual religious practices, intrinsic religiosity, and daily spiritual experiences. Mixed effects growth curve models were used to compare the effects of treatment group on trajectory of change in optimism. Results In the intention‐to‐treat analysis, both RCBT and SCBT increased optimism over time, although there was no significant difference between treatment groups (B = –0.75, SE = 0.57, t = –1.33, P = .185). Analyses in the highly religious and in the per protocol analysis indicated similar results. Higher baseline religiosity predicted an increase in optimism over time (B = 0.07, SE = 0.02, t = 4.12, P < .0001), and higher baseline optimism predicted a faster decline in depressive symptoms over time (B = −0.61, SE = 0.10, t = −6.30, P < .0001), both independent of treatment group. Conclusions RCBT and SCBT are equally effective in increasing optimism in persons with MDD and chronic medical illness. While baseline religiosity does not moderate this effect, religiosity predicts increases in optimism over time independent of treatment group.

  July 28, 2015   doi: 10.1002/da.22398   open full text
• Factors Associated With Posttraumatic Stress Disorder Following Moderate To Severe Traumatic Brain Injury: A Prospective Study.
  Yvette Alway, Adam McKay, Kate Rachel Gould, Lisa Johnston, Jennie Ponsford.
  Depression and Anxiety. July 28, 2015
  Background This study prospectively examined the relationship between preinjury, injury‐related, and postinjury factors and posttraumatic stress disorder (PTSD) following moderate to severe traumatic brain injury (TBI). Method Two hundred and three participants were recruited during inpatient admission following moderate to severe TBI. Participants completed an initial assessment soon after injury and were reassessed at 3, 6, and 12 months, 2, 3, 4, and 5 years postinjury. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders–fourth edition was used to diagnose pre‐ and postinjury PTSD and other psychiatric disorders. The Glasgow Outcome Scale‐Extended (GOSE) and the Quality of Life Inventory (QOLI) were used to evaluate functional and psychosocial outcome from 6 months postinjury. Results The frequency of PTSD ranged between 0.5 and 9.4% during the 5‐year period, increasing throughout the first 12 months and declining thereafter. After controlling for other predictors, shorter posttraumatic amnesia duration (odds ratio = 0.96, 95% CI = 0.92–1.00), other concurrent psychiatric disorder (odds ratio = 14.22, 95% CI = 2.68–75.38), and lower GOSE (odds ratio = 0.38, 95% CI = 0.20–0.72) and QOLI scores (odds ratio = 0.97, 95% CI = 0.95–0.97) were associated with greater odds of having injury‐related PTSD. Discussion The results of this study indicate that while shorter posttraumatic amnesia duration is associated with PTSD, greater TBI severity does not prevent PTSD from evolving. Patients with PTSD experienced high rates of psychiatric comorbidity and poorer functional and quality of life outcomes after TBI. Conclusion There is a need to direct clinical attention to early identification and treatment of PTSD following TBI to improve outcomes.

  July 28, 2015   doi: 10.1002/da.22396   open full text
• Orbitofrontal Thickness As A Measure For Treatment Response Prediction In Obsessive–Compulsive Disorder.
  Marcelo Q. Hoexter, Juliana B. Diniz, Antonio C. Lopes, Marcelo C. Batistuzzo, Roseli G. Shavitt, Darin D. Dougherty, Fabio L. S. Duran, Rodrigo A. Bressan, Geraldo F. Busatto, Euripides C. Miguel, Joao R. Sato.
  Depression and Anxiety. May 29, 2015
  Background Early prediction of treatment response could reduce exposure to ineffective treatments and optimize the use of medical resources. Neuroimaging techniques have been used to identify biomarkers that are predictive of outcomes. The aims of this study were to investigate orbitofrontal cortex (OFC) thickness as a potential morphometric biomarker to discriminate outcomes in obsessive–compulsive disorder (OCD) and then to reexamine this biomarker in an independent cohort Methods Using a logistic regression model based on the mean baseline thickness of subregions of the OFC, we estimated the probability of treatment response in 29 treatment‐naïve OCD patients who participated in a clinical trial. That algorithm was then tested in an independent cohort of 12 patients with a confirmed diagnosis of refractory OCD Results Among the treatment‐naïve OCD patients, measures of OFC thickness statistically significantly differentiated responders (n = 13) and nonresponders (n = 16), with an overall classification accuracy of ≈80%, a sensitivity of 77% (10/13), and a specificity of 81% (13/16). Of the refractory OCD patients in the second independent cohort, 67% were correctly classified as nonresponders. The most discriminative measures in the initial cohort of treatment‐naïve patients were the thicknesses of the left and right medial OFC (P = .009 and P = .028, respectively) Conclusions We found OFC thickness to be a strong predictor of treatment response in treatment‐naïve OCD patients. Although there are not yet any brain imaging biomarkers with clinical utility, our results highlight the potential of these measures as tools for predicting treatment outcomes in OCD.

  May 29, 2015   doi: 10.1002/da.22380   open full text
• Longitudinal Course Of Posttraumatic Growth Among U.S. Military Veterans: Results From The National Health And Resilience In Veterans Study.
  Jack Tsai, Lauren M. Sippel, Natalie Mota, Steven M. Southwick, Robert H. Pietrzak.
  Depression and Anxiety. April 23, 2015
  Background Posttraumatic growth (PTG) is increasingly recognized as an important psychosocial phenomenon, but few studies have evaluated the longitudinal course of PTG. This study identified courses of PTG over a 2‐year period in a contemporary, nationally representative sample of U.S. military veterans, and examined sociodemographic, military, trauma, medical, and psychosocial predictors of PTG course. Methods Data were based on a Web‐based survey of a nationally representative sample of 1,838 U.S. veterans who reported at least one potentially traumatic event and provided data at two time points (October–December 2011 and September–October 2013). Results Five different courses of PTG were identified—Consistently Low (33.6%), Moderately Declining (19.4%), Increasing PTG (16.8%), Dramatically Declining (15.7%), and Consistently High (14.5%). More than half (59.4%) of veterans who reported at least “moderate” PTG maintained that level of PTG 2 years later. Posttraumatic stress disorder symptoms, medical conditions, purpose in life, altruism, gratitude, religiosity, and an active reading lifestyle predicted maintenance or increase in PTG. Conclusions PTG has a heterogeneous course and is not only common, but can persist over time especially in the presence of posttraumatic stress and certain psychosocial factors. Clinicians and researchers should consider the personal growth that can result from trauma and help trauma survivors find ways to maintain this growth over time.

  April 23, 2015   doi: 10.1002/da.22371   open full text
• Sex Differences In Help Seeking For Mood And Anxiety Disorders In The National Comorbidity Survey‐Replication.
  Ryoko Susukida, Ramin Mojtabai, Tamar Mendelson.
  Depression and Anxiety. April 22, 2015
  Background Past research has consistently found that men are less likely to seek help for mental disorders than women. However, the reasons for this difference are not clear. This study explored whether sex differences in attitudes toward help seeking, perceived interference caused by mental disorders, and attending routine medical visits could explain sex differences in help seeking. Methods Analyses focused on 1,963 participants who met DSM‐IV diagnostic criteria for a 12‐month mood or anxiety disorder in the National Comorbidity Survey‐Replication (NCS‐R). Multiple logistic regression analyses were conducted to examine sex differences in help seeking from different types of providers after adjusting for attitudes toward help seeking, perceived interference in functioning, attending routine medical visits, and sociodemographic factors. Results While men were less likely than women to seek help from health care providers, this difference was limited to seeking care from medical doctors and informal services. Men were as likely to seek help from mental health professionals as women. Men's lower likelihood of attending routine medical visits as compared with women partially explained the sex difference in help seeking from medical doctors. In contrast, attitudes toward help seeking did not explain much of the sex differences in help seeking from medical doctors. Conclusions Efforts aimed at reducing attitudinal barriers toward treatment seeking for mental disorders may not effectively reduce the sex disparity in mental health help seeking. The results highlight the importance of encouraging men to attend routine medical visits, as medical doctors are a key gateway to mental health services.

  April 22, 2015   doi: 10.1002/da.22366   open full text
• Are Women's Parenting‐Specific Beliefs Associated With Depressive Symptoms In The Perinatal Period? Development Of The Rigidity Of Maternal Beliefs Scale.
  Elizabeth Thomason, Heather A. Flynn, Joseph A. Himle, Brenda L. Volling.
  Depression and Anxiety. May 29, 2014
  Background Perinatal depression negatively impacts women, parenting, and children's development. However, not much is known about maternal specific beliefs that may be associated with perinatal depression. We created a new measure that examined the rigidity of perinatal women's beliefs in three major domains suggested to be closely related to mood and behavior: anticipated maternal self‐efficacy, perceptions of child vulnerability, and perceptions of societal expectations of mothers (PSEM). Methods A 26‐item measure (the Rigidity of Maternal Beliefs Scale, RMBS) was developed and completed by women at two time points, pregnancy (n = 134) and postpartum (n = 113), along with the Edinburgh Postnatal Depression Scale. Exploratory factor analysis (EFA) examined the factor structure of the RMBS and validity and reliability were also tested. Results The EFA suggested that a four‐factor solution was most interpretable, with few items cross‐loading, and there were common themes that unified the items in each factor, resulting in a 24‐item final measure. Cronbach's alpha confirmed the internal consistency, whereas bivariate correlations revealed the measure had good test‐retest reliability, discriminant validity, and convergent validity. Regression analyses established predictive validity of the RMBS for postpartum depressive symptoms. Conclusions The RMBS may be useful with clinical populations to identify maladaptive or rigid thoughts that could be a focus of intervention. This tool may also be used to guide conversation about motherhood expectations within any context where pregnant women present (e.g., prenatal care, social services), as well as potentially identifying women who are at risk for postpartum depression in clinical contexts.

  May 29, 2014   doi: 10.1002/da.22280   open full text
• Long‐Term Outcomes Among Child And Adolescent Survivors Of The 2010 Haitian Earthquake.
  Jude Mary Cénat, Daniel Derivois.
  Depression and Anxiety. May 29, 2014
  Background We examined the prevalence and predictive factors of PTSD and depression in relation with peritraumatic distress, trauma exposure, and sociodemographic characteristics among children and adolescent who survived the 2010 Haiti's earthquake. Methods We analyzed data collected between June and July 2012 from a sample of 872 participants aged 7 to 17 in 12 schools, door‐to‐door canvassing and two centers for street children at Port‐au‐Prince. Participants completed the Impact of Event Scale Revised (IES‐R), Peritraumatic Distress Inventory, Child Depression Inventory 2 (CDI), and sociodemographic and traumatic exposure questionnaires. Results Of 872 participants, respectively 322 (36.93%); and 403 (46.21%) reported a clinically significant symptoms of PTSD and depression, which were significantly higher among girls. The best predictive variables are peritraumatic distress for PTSD (β=0.53,P<.0001) a traumatic exposure for depression (β=0.23,P<.0001). The comorbidity between PTSD and depression symptoms is 22.25%. Conclusions This first study in children on the prevalence of PTSD and depression resulting from the 2010 Haiti earthquake demonstrates a need for improvement in treatment aimed at reducing PTSD and depression. Such treatment should be geared primarily toward girls, adolescents between the ages of 14 and 17 and those children and adolescents who have lost a family member in the earthquake.

  May 29, 2014   doi: 10.1002/da.22275   open full text
• Anxiety In Major Depression And Cerebrospinal Fluid Free Gamma‐Aminobutyric Acid.
  J. John Mann, Maria A. Oquendo, Kalycia Trishana Watson, Maura Boldrini, Kevin M. Malone, Steven P. Ellis, Gregory Sullivan, Thomas B. Cooper, Shan Xie, Dianne Currier.
  Depression and Anxiety. May 27, 2014
  Background Low gamma‐aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. Methods and Materials Patients with a DSM‐IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. Results Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. Conclusions Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment‐resistant anxious major depression and in older patients.

  May 27, 2014   doi: 10.1002/da.22278   open full text
• Adjustment Among Children With Relatives Who Participated In The Manhunt Following The Boston Marathon Attack.
  Jonathan S. Comer, Caroline E. Kerns, R. Meredith Elkins, Aubrey L. Edson, Tommy Chou, Annie Dantowitz, Elizabeth Miguel, Bonnie Brown, Stefany Coxe, Jennifer Greif Green.
  Depression and Anxiety. May 27, 2014
  Background Following the Boston Marathon attack, the extraordinary interagency manhunt and shelter‐in‐place made for a truly unprecedented experience for area families. Although research on Boston youth has found robust associations between manhunt‐related experiences and post‐attack functioning, such work does little to identify the specific needs of a particularly vulnerable population—i.e., children with a relative who participated in the manhunt. Understanding the adjustment of these youth is critical for informing clinical efforts. Methods Survey of Boston‐area parents/caretakers (N = 460) reporting on their child's attack/manhunt‐related experiences, as well as psychosocial functioning in the first six post‐attack months; analyses compared youth with and without a relative in law enforcement or the armed services who participated in the manhunt. Results The proportion of youth with likely PTSD was 5.7 times higher among youth with relatives in the manhunt than among youth without. After accounting for child demographics, blast exposure, and children's own exposure to manhunt events (e.g., hearing/seeing gunfire/explosions, having officers enter/search home), having a relative in the manhunt significantly predicted child PTSD symptoms, emotional symptoms, and hyperactivity/inattention. Fear during the manhunt that a loved one could be hurt mediated relationships between having a relative in the manhunt and clinical outcomes; living within the zone of greatest manhunt activity did not moderate observed relationships. Conclusions Children with relatives called upon to participate in the unprecedented interagency manhunt following the Boston Marathon attack carried a particularly heavy mental health burden. Continued research is needed to clarify the clinical needs of youth with relatives in high‐risk occupations.

  May 27, 2014   doi: 10.1002/da.22281   open full text
• Neural Correlates Of Risky Decision Making In Anxious Youth And Healthy Controls.
  Adriana Galván, Tara S. Peris.
  Depression and Anxiety. May 27, 2014
  Background Pediatric anxiety disorders are chronic and impairing conditions that are characterized by risk aversion and avoidance; however, the neural correlates of decision making under risk in anxious youth remain poorly understood. Methods Youth with a primary diagnosis of separation anxiety, social phobia, or generalized anxiety disorder (n = 16) and healthy controls (n = 15), performed a risky decision‐making task under conditions of potential gain or loss while undergoing a functional magnetic resonance imaging (fMRI) scan. Results Analyses were conducted to examine neural response to risky versus nonrisky choices in each condition. Anxious youth made fewer risky choices during potential loss compared to controls. Both groups elicited strong frontostriatal activation during risky choice. During risky choice in the gain condition, controls exhibited greater activation in ventral putamen during risky choice than during nonrisky choice and than anxious youth. In the loss condition, controls exhibited greater activation in medial prefrontal cortex during risk‐taking while anxious youth exhibited greater engagement of amygdala and insula. Neural activation during risky choice was associated with individual differences in anxiety symptom severity, such that as anxiety symptomatology increased, there was decreased recruitment of the ventral striatum in the gain condition and increasing recruitment of the amygdala in the loss condition. Conclusions Youth with anxiety disorders differ from their nonanxious peers on both behavioral and neurobiological indices during risky decision making; these differences are exacerbated by symptom severity and they shed light on the pathophysiology of pediatric anxiety. Neural correlates of risky decision making in anxious youth and healthy controls

  May 27, 2014   doi: 10.1002/da.22276   open full text
• Cognitive‐Behavioral Therapy For Panic Disorder With Agoraphobia In Older People: A Comparison With Younger Patients.
  Gert‐Jan Hendriks, Mirjam Kampman, Ger P.J. Keijsers, Cees A. L. Hoogduin, Richard C. Oude Voshaar.
  Depression and Anxiety. May 27, 2014
  Background Older adults with panic disorder and agoraphobia (PDA) are underdiagnosed and undertreated, while studies of cognitive‐behavioral therapy (CBT) are lacking. This study compares the effectiveness of CBT for PDA in younger and older adults. Methods A total of 172 patients with PDA (DSM‐IV) received manualized CBT. Primary outcome measures were avoidance behavior (Mobility Inventory Avoidance scale) and agoraphobic cognitions (Agoraphobic Cognitions Questionnaire), with values of the younger (18–60 years) and older (≥60 years) patients being compared using mixed linear models adjusted for baseline inequalities, and predictive effects of chronological age, age at PDA onset and duration of illness (DOI) being examined using multiple linear regressions. Results Attrition rates were 2/31 (6%) for the over‐60s and 31/141 (22%) for the under‐60s group (χ2 = 3.43, df = 1, P = .06). Patients in both age groups improved on all outcome measures with moderate‐to‐large effect sizes. Avoidance behavior had improved significantly more in the 60+ group (F = 4.52, df = 1,134, P = .035), with agoraphobic cognitions showing no age‐related differences. Baseline severity of agoraphobic avoidance and agoraphobic cognitions were the most salient predictors of outcome (range standardized betas 0.59 through 0.76, all P‐values < .001). Apart from a superior reduction of agoraphobic avoidance in the 60+ participants (β = −0.30, P = .037), chronological age was not related to outcome, while in the older patients higher chronological age, late‐onset type and short DOI were linked to superior improvement of agoraphobic avoidance. Conclusions CBT appears feasible for 60+ PDA‐patients, yielding outcomes that are similar and sometimes even superior to those obtained in younger patients.

  May 27, 2014   doi: 10.1002/da.22274   open full text
• Prevalence Of Psychiatric Disorders And Functional Impairment After Loss Of A Family Member: A Longitudinal Study After The 2004 Tsunami.
  Pål Kristensen, Lars Weisæth, Ajmal Hussain, Trond Heir.
  Depression and Anxiety. May 09, 2014
  Background Bereavement following disasters is a devastating experience for family members. The aim of this study was to examine the long‐term mental health effects of losing a loved one in a natural disaster. Methods Ninety‐four Norwegians aged 18–80 years who lost close family members in the 2004 Southeast Asian tsunami were evaluated 2 and 6 years after the disaster. The participants were either staying in an affected area at the time of the disaster (i.e., directly exposed) or not (i.e., not directly exposed). The prevalence of psychiatric disorders was assessed by the MINI International Neuropsychiatric Interview (M.I.N.I). Prolonged grief disorder (PGD) was self‐reported using the Inventory of Complicated Grief (ICG), and functional impairment was self‐reported using the Work and Social Adjustment Scale (WSAS). Results We did not identify a significant decrease in the prevalence of PGD, posttraumatic stress disorder (PTSD), or major depressive disorder (MDD) from 2 to 6 years. Approximately, one‐third of the bereaved (36%) had a psychiatric disorder 6 years after the tsunami. The most common disorder was PGD (12%) followed by general anxiety disorder (GAD, 11%), agoraphobia (11%), and MDD (10%). The prevalence of PTSD and MDD was higher among family members who were directly exposed to the disaster compared to those who were not (21 vs. 0%, and 25 vs. 3%). PGD was associated with functional impairment independent of other disorders. Conclusions Loss of a close family member in a natural disaster can have a substantial adverse long‐term effect on mental health and everyday functioning.

  May 09, 2014   doi: 10.1002/da.22269   open full text
• The Relationship Between Maternal Depressive, Anxious, And Stress Symptoms During Pregnancy And Adult Offspring Behavioral And Emotional Problems.
  Kim S. Betts, Gail M. Williams, Jakob M. Najman, Rosa Alati.
  Depression and Anxiety. April 30, 2014
  Background Prenatal maternal depressive, anxious, and stress symptoms have been found to be associated with child and adolescent behavior problems. In this paper, we investigate their impact on behavior problems and depressive symptoms in adulthood. Methods Participants included 3,099 mother–offspring pairs from the Mater University Study of Pregnancy (MUSP), an Australian based, prebirth cohort study. We used latent class growth analysis (LCGA) with parallel processes to identify trajectories of maternal depressive, anxious, and stress symptoms over four time periods between the mothers’ first clinic visit and 5 years postpregnancy. We fitted the estimates from the maternal trajectories in multivariate logistic regression models to predict internalizing and externalizing behavior at age 21. We adjusted for a wide range of prenatal and postnatal factors, including maternal life events, relationship quality, contact with the new born, as well as concurrent maternal depressive and anxious symptoms and father's history of mental health problem. Results LCGA found seven groups of mothers; one group of mothers exhibited high levels of depressive, anxious, and stress symptoms during pregnancy but not at later time points. Their offspring experienced increased levels of behavior problems and depressive symptoms. Conclusions This paper provides the first evidence that high levels of maternal subjective depressive, anxious, and stress symptoms experienced in early pregnancy may predict internalizing and externalizing behavior problems and depressive symptoms in young adults.

  April 30, 2014   doi: 10.1002/da.22272   open full text
• Peer Victimization During Adolescence And Risk For Anxiety Disorders In Adulthood: A Prospective Cohort Study.
  Lexine A. Stapinski, Lucy Bowes, Dieter Wolke, Rebecca M. Pearson, Liam Mahedy, Katherine S. Button, Glyn Lewis, Ricardo Araya.
  Depression and Anxiety. April 30, 2014
  Background Peer victimization is ubiquitous across schools and cultures, and has been suggested as one developmental pathway to anxiety disorders. However, there is a dearth of prospective studies examining this relationship. The purpose of this cohort study was to examine the association between peer victimization during adolescence and subsequent anxiety diagnoses in adulthood. A secondary aim was to investigate whether victimization increases risk for severe anxiety presentations involving diagnostic comorbidity. Methods The sample comprised 6,208 adolescents from the Avon Longitudinal Study of Parents and Children who were interviewed about experiences of peer victimization at age 13. Maternal report of her child's victimization was also assessed. Anxiety disorders at age 18 were assessed with the Clinical Interview Schedule–Revised. Multivariable logistic regression was used to examine the association between victimization and anxiety diagnoses adjusted for potentially confounding individual and family factors. Sensitivity analyses explored whether the association was independent of diagnostic comorbidity with depression. Results Frequently victimized adolescents were two to three times more likely to develop an anxiety disorder than nonvictimized adolescents (OR = 2.49, 95% CI: 1.62–3.85). The association remained after adjustment for potentially confounding individual and family factors, and was not attributable to diagnostic overlap with depression. Frequently victimized adolescents were also more likely to develop multiple internalizing diagnoses in adulthood. Conclusions Victimized adolescents are at increased risk of anxiety disorders in later life. Interventions to reduce peer victimization and provide support for victims may be an effective strategy for reducing the burden associated with these disorders.

  April 30, 2014   doi: 10.1002/da.22270   open full text
• Effects Of Antenatal Yoga On Maternal Anxiety And Depression: A Randomized Controlled Trial.
  James J. Newham, Anja Wittkowski, Janine Hurley, John D. Aplin, Melissa Westwood.
  Depression and Anxiety. April 30, 2014
  Background Antenatal depression and anxiety are associated with adverse obstetric and mental health outcomes, yet practicable nonpharmacological therapies, particularly for the latter, are lacking. Yoga incorporates relaxation and breathing techniques with postures that can be customized for pregnant women. This study tested the efficacy of yoga as an intervention for reducing maternal anxiety during pregnancy. Methods Fifty‐nine primiparous, low‐risk pregnant women completed questionnaires assessing state (State Trait Anxiety Inventory; STAI‐State), trait (STAI‐Trait), and pregnancy‐specific anxiety (Wijma Delivery Expectancy Questionnaire; WDEQ) and depression (Edinburgh Postnatal Depression Scale; EPDS) before randomization (baseline) to either an 8‐week course of antenatal yoga or treatment‐as‐usual (TAU); both groups repeated the questionnaires at follow‐up. The yoga group also completed pre‐ and postsession state anxiety and stress hormone assessments at both the first and last session of the 8‐week course. Results A single session of yoga reduced both subjective and physiological measures of state anxiety (STAI‐S and cortisol); and this class‐induced reduction in anxiety remained at the final session of the intervention. Multiple linear regression analyses identified allocation to yoga as predictive of greater reduction in WDEQ scores (B = −9.59; BCa 95% CI = −18.25 to −0.43; P = .014; d = −0.57), while allocation to TAU was predictive of significantly increased elevation in EPDS scores (B = −3.06; BCa 95% CI = −5.9 to −0.17; P = .042; d = −0.5). No significant differences were observed in state or trait anxiety scores between baseline and follow‐up. Conclusion Antenatal yoga seems to be useful for reducing women's anxieties toward childbirth and preventing increases in depressive symptomatology.

  April 30, 2014   doi: 10.1002/da.22268   open full text
• Cognitive‐Emotional Training As An Intervention For Major Depressive Disorder.
  Brian M. Iacoviello, Gang Wu, Evan Alvarez, Kathryn Huryk, Katherine A. Collins, James W. Murrough, Dan V. Iosifescu, Dennis S. Charney.
  Depression and Anxiety. April 17, 2014
  Background There is an urgent need for more effective treatments for major depressive disorder (MDD). As understanding of the cognitive and affective neuroscience underlying psychiatric disorders expands, so do opportunities to develop interventions that capitalize on the capacity for brain plasticity. Cognitive training is one such strategy. In this article, we report a proof‐of‐concept study of a novel cognitive‐emotional training exercise designed to enhance cognitive control for emotional information processing and targeting components of the neural networks that have been implicated in MDD. Methods Twenty‐one participants with MDD in a current episode were randomly assigned to one of the two treatment conditions: 11 participating in a cognitive‐emotional training paradigm (emotional faces memory task (EFMT)) involving eight sessions over 4 weeks, and 10 participating in an active control condition (control training, CT). Assessments of MDD symptoms, negative affective bias in cognitive processing, and neurocognition (attention and working memory) were administered at baseline and after 4 weeks. Results Participants in the EFMT group exhibited a greater reduction in MDD symptoms compared to the CT group, and 6 of the 11 EFMT participants achieved clinical response (≥50% reduction in symptoms). EFMT participants also exhibited changes in negative affective bias in the hypothesized direction whereas the CT participants did not. Both groups exhibited similar, small improvements in attention and working memory. Conclusions Cognitive‐emotional training may represent a feasible and effective intervention strategy for MDD. This proof‐of‐concept study highlights the need for future studies to fully understand the effectiveness, and mechanisms of effect, of these training strategies.

  April 17, 2014   doi: 10.1002/da.22266   open full text
• Neurocircuitry Underlying Risk And Resilience To Social Anxiety Disorder.
  Jacqueline A. Clauss, Suzanne N. Avery, Ross M. VanDerKlok, Baxter P. Rogers, Ronald L. Cowan, Margaret M. Benningfield, Jennifer Urbano Blackford.
  Depression and Anxiety. April 17, 2014
  Background Almost half of children with an inhibited temperament will develop social anxiety disorder by late adolescence. Importantly, this means that half of children with an inhibited temperament will not develop social anxiety disorder. Studying adults with an inhibited temperament provides a unique opportunity to identify neural signatures of both risk and resilience to social anxiety disorder. Methods Functional magnetic resonance imaging (fMRI) was used to measure brain activation during the anticipation of viewing fear faces in 34 young adults (17 inhibited, 17 uninhibited). To identify neural signatures of risk, we tested for group differences in functional activation and connectivity in regions implicated in social anxiety disorder, including the prefrontal cortex, amygdala, and insula. To identify neural signatures of resilience, we tested for correlations between brain activation and both emotion regulation and social anxiety scores. Results Inhibited subjects had greater activation of a prefrontal network when anticipating viewing fear faces, relative to uninhibited subjects. No group differences were identified in the amygdala. Inhibited subjects had more negative connectivity between the rostral anterior cingulate cortex (ACC) and the bilateral amygdala. Within the inhibited group, those with fewer social anxiety symptoms and better emotion regulation skills had greater ACC activation and greater functional connectivity between the ACC and amygdala. Conclusions These findings suggest that engaging regulatory prefrontal regions during anticipation may be a protective factor, or putative neural marker of resilience, in high‐risk individuals. Cognitive training targeting prefrontal cortex function may provide protection against anxiety, especially in high‐risk individuals, such as those with inhibited temperament.

  April 17, 2014   doi: 10.1002/da.22265   open full text
• Neuropsychological Function Before And After Subcallosal Cingulate Deep Brain Stimulation In Patients With Treatment‐Resistant Depression.
  Jared L. Moreines, Shawn M. McClintock, Mary E. Kelley, Paul E. Holtzheimer, Helen S. Mayberg.
  Depression and Anxiety. April 17, 2014
  Background Treatment‐resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD. Methods Patients with TRD (N = 17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm. Results Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable. Conclusions Patients with TRD show slowed processing speed but otherwise largely preserved neuropsychological functioning. DBS of the SCCwm does not result in worsening of any aspect of neuropsychological function and may improve certain domains. Future research is warranted to better understand the effects of TRD and DBS on neuropsychological function.

  April 17, 2014   doi: 10.1002/da.22263   open full text
• Transdiagnostic Dimensions Of Anxiety And Depression Moderate Motivation‐Related Brain Networks During Goal Maintenance.
  Jeffrey M. Spielberg, Gregory A. Miller, Stacie L. Warren, Bradley P. Sutton, Marie Banich, Wendy Heller.
  Depression and Anxiety. April 17, 2014
  Background Advancing research on the etiology, prevention, and treatment of psychopathology requires the field to move beyond modular conceptualizations of neural dysfunction toward understanding disturbance in key brain networks. Although some studies of anxiety and depression have begun doing so, they typically suffer from several drawbacks, including: (1) a categorical approach ignoring transdiagnostic processes, (2) failure to account for substantial anxiety and depression comorbidity, (3) examination of networks at rest, which overlooks disruption manifesting only when networks are challenged. Accordingly, the present study examined relationships between transdiagnostic dimensions of anxiety/depression and patterns of functional connectivity while goal maintenance was challenged. Methods Participants (n = 179, unselected community members and undergraduates selected to be high/low on anxiety/depression) performed a task in which goal maintenance was challenged (color‐word Stroop) while fMRI data were collected. Analyses examined moderation by anxiety/depression of condition‐dependent coupling between regions of dorsolateral prefrontal cortex (dlPFC) previously associated with approach and avoidance motivation and amygdala/orbitofrontal cortex (OFC). Results Anxious arousal was positively associated with amygdala↔right dlPFC coupling. Depression was positively associated with OFC↔right dlPFC coupling and negatively associated with OFC↔left dlPFC coupling. Conclusions Findings advance the field toward an integrative model of the neural instantiation of anxiety/depression by identifying specific, distinct dysfunctions associated with anxiety and depression in networks important for maintaining approach and avoidance goals. Specifically, findings shed light on potential neural mechanisms involved in attentional biases in anxiety and valuation biases in depression and underscore the importance of examining transdiagnostic dimensions of anxiety/depression while networks are challenged.

  April 17, 2014   doi: 10.1002/da.22271   open full text
• Stress Exposure Across The Life Span Cumulatively Increases Depression Risk And Is Moderated By Neuroticism.
  Christiaan H. Vinkers, Marian Joëls, Yuri Milaneschi, René S. Kahn, Brenda W.J.H. Penninx, Marco P.M. Boks.
  Depression and Anxiety. April 17, 2014
  Background Even though traumatic stress is a major risk factor for depression, most people do not develop a depression. The effects of stress may particularly emerge after repeated exposure in vulnerable individuals. Therefore, we hypothesized that (1) increased exposure to stress across the life span is associated with an increased depression risk and (2) this effect is the most pronounced in individuals with high levels of neuroticism. Methods We investigated the effect of childhood maltreatment, major life events, daily hassles, and a composite index thereof (cumulative stress index) on depressive symptoms and major depressive disorder (MDD) including the possible moderating role of neuroticism in a discovery sample from the general population (N = 563) and an independent replication sample from the Netherlands Study of Depression and Anxiety (N = 2,274). Results All stress domains were independently associated with depressive symptoms in the discovery sample. In the replication sample, we confirmed these findings for childhood maltreatment and daily hassles but not for major life events with depressive symptoms as outcome. Nevertheless, all stress domains significantly contributed to the presence of MDD in the replication sample. The cumulative stress index was significantly associated with depression in the discovery (β = 1.42, P < .001) and replication sample (β = 3.79, P < .001), especially in those individuals with high levels of trait neuroticism (discovery: β = 0.013, P < .001; replication: β = 0.367, P < .001). Conclusions This is the first study to show that cumulative stress exposure across different stress domains contributes to depressive symptoms and MDD in adulthood. Moreover, we show that increased exposure to stress across the life span has more impact on vulnerable individuals with high levels of trait neuroticism.

  April 17, 2014   doi: 10.1002/da.22262   open full text
• Effectiveness Of Cognitive Behavioral Therapy For Insomnia: Influence Of Slight‐To‐Moderate Depressive Symptom Severity And Worrying.
  Astrid B. H. Hamoen, Else M. Redlich, Al W. Weerd.
  Depression and Anxiety. April 04, 2014
  Background Cognitive behavioral therapy for insomnia (CBT‐I) is a well‐known, effective treatment for primary insomnia. However, the majority of sleeping problems occur in the presence of another medical or psychiatric disorder. Depression and general anxiety disorder (with a main feature of excessive generalized worrying) are disorders that frequently co‐occur with insomnia. The purpose of this study is to evaluate whether depressive symptom severity or worrying influences the subjective effectiveness of CBT‐I. Methods Patients with a complaint of insomnia received CBT‐I. At the beginning of the therapy, patients completed a sleep evaluation list, the Beck Depression Inventory (BDI‐II‐NL, N = 92), and the Penn State Worry Questionnaire (PSWQ, N = 119). Based on the BDI and the PSWQ, the sample was divided into different groups: patients with low versus high depression scores, low worriers versus high worriers, and patients without depressive symptoms who were also classified as low worriers and patients with depressive symptoms who were also classified as high worriers. The sleep evaluation list was completed directly after the treatment and 6 months later. Results Sleep evaluation scores, subjective total sleep time, subjective sleep onset latency, and subjective wake after sleep onset all changed in a positive way after CBT‐I and remained that way over the next 6 months for all patients. These positive effects of CBT‐I did not differ between the subgroups. Conclusions Results suggest that CBT‐I improves subjective sleep experiences, regardless of depressive symptom severity or worrying.

  April 04, 2014   doi: 10.1002/da.22258   open full text
• Epidemiology And Course Of Unipolar Mania: Results From The National Epidemiologic Survey On Alcohol And Related Conditions (Nesarc).
  Ji Hyun Baek, Lori R. Eisner, Andrew A. Nierenberg.
  Depression and Anxiety. March 27, 2014
  Background Unipolar mania (UM), in which only manic episodes occur during the course of illness, may be an important clinical manifestation of bipolar disorder that is under‐recognized and understudied. The aim of this study is, for the first time, to examine the prevalence of UM and its clinical characteristics in the community. Methods Among a total of 1,411 subjects with bipolar I disorder, we evaluated the prevalence of UM using three different criteria proposed in previous studies. We compared the clinical characteristics of subjects with UM to those with a more classic bipolar presentation with mania and lifetime major depressive episode (MDE). We additionally explored the proportion of subjects with UM who later experience at least one MDE during a 3‐year follow‐up period and determined risk factors for converting from UM to classic bipolar disorder. Results The prevalence rate of UM among those with bipolar disorder ranged from 5.0 to 7.2% depending on the criteria. UM was more common in male and nonwhite subjects. About half of individuals with UM experienced subthreshold depression. Individuals with UM had lower rates of comorbid anxiety disorders or attention deficit hyperactivity disorder (ADHD). During the follow‐up, about 18% of subjects with UM experienced MDEs. Male, nonwhite, comorbid generalized anxiety disorder and ADHD predicted an increased transition from UM to classic bipolar disorder. Subthreshold depression was not associated with the risk of the transition. Conclusions UM is an infrequent but clinically distinct subtype of bipolar I disorder. Further research delineating the characteristics of UM is warranted.

  March 27, 2014   doi: 10.1002/da.22261   open full text
• C'mon Get Happy: Reduced Magnitude And Duration Of Response During A Positive‐Affect Induction In Depression.
  Michelle S. Horner, Greg J. Siegle, Robert M. Schwartz, Rebecca B. Price, Agnes E. Haggerty, Amanda Collier, Edward S. Friedman.
  Depression and Anxiety. March 18, 2014
  Background Depression involves decreased positive affect. Whether this is due to a failure to achieve or maintain positive emotion in response to discrete stimuli is unclear. Understanding the nature of decreased positive affect could help to address how to intervene in the phenomenon, for example, how to structure interventions using positive and rewarding stimuli in depression. Thus, we examined the time course of affect following exposure to positive stimuli in depressed and healthy individuals. Methods Seventy‐one adults with major depressive disorder and thirty‐four never‐depressed controls read a self‐generated highly positive script and continuously rated their affect for 7 min. Results Both groups quickly achieved increased positive affect, however, compared to controls, depressed participants did not achieve the same level of positive affect, did not maintain their positive affect, spent less time rating their affect as happy, and demonstrated larger drops in mood. Conclusions These data indicate that depressed and nondepressed individuals can generate positive reactions to happy scripts, but depressed individuals cannot achieve or sustain equivalent levels of positive affect. Interventions for depression might fruitfully focus on increasing depressed individuals’ ability to maintain initial engagement with positive stimuli over a sustained period of time.

  March 18, 2014   doi: 10.1002/da.22244   open full text
• Early Risk Factors For Psychopathology In Offspring Of Parents With Bipolar Disorder: The Role Of Obstetric Complications And Maternal Comorbid Anxiety.
  Rachel D. Freed, Martha C. Tompson, Michael W. Otto, Andrew A. Nierenberg, Dina Hirshfeld‐Becker, Christine H. Wang, Aude Henin.
  Depression and Anxiety. March 18, 2014
  Objective Offspring of parents with bipolar disorder (BD) are at increased risk for developing a range of psychiatric disorders. Although genetic factors clearly confer risk to offspring, environmental factors also play a role in increasing vulnerability. Such environmental factors may occur at the initial stages of development in the form of obstetric complications (OCs). The current investigation examined the relationship between OCs and the development of psychopathology in offspring at risk for BD and the influence of parental psychopathology in this relationship. Methods This cross‐sectional study included 206 offspring of 119 parents with BD. Probit regression analyses examined associations between: (1) OC history and offspring psychopathology; and (2) maternal lifetime comorbid anxiety diagnoses and OCs in pregnancy/delivery with their offspring. Path analyses then tested whether OCs mediate the relationship between maternal comorbid anxiety disorders and offspring lifetime psychopathology. Results Results indicated a specific association between OCs, particularly delivery complications, and increased risk for offspring anxiety disorders. Data also showed a significant relationship between maternal anxiety disorder comorbidity and OCs. Finally, path analyses suggested that delivery complications act as a mediator in the relationship between comorbid maternal anxiety disorder and offspring anxiety disorder. Conclusions Our findings lend support to the importance of identifying and reducing anxiety in pregnant woman with BD. The identification of OCs as early vulnerability factors for psychopathology in offspring at familial risk may also lead to earlier detection and intervention in these offspring.

  March 18, 2014   doi: 10.1002/da.22254   open full text
• Changes In Self‐Efficacy And Outcome Expectancy As Predictors Of Anxiety Outcomes From The Calm Study.
  Lily A. Brown, Joshua F. Wiley, Kate Wolitzky‐Taylor, Peter Roy‐Byrne, Cathy Sherbourne, Murray B. Stein, Greer Sullivan, Raphael D. Rose, Alexander Bystritsky, Michelle G. Craske.
  Depression and Anxiety. March 11, 2014
  Background Although self‐efficacy (SE) and outcome expectancy (OE) have been well researched as predictors of outcome, few studies have investigated changes in these variables across treatments. We evaluated changes in OE and SE throughout treatment as predictors of outcomes in a large sample with panic disorder, generalized anxiety disorder, social anxiety disorder, or posttraumatic stress disorder. We hypothesized that increases in SE and OE would predict reductions in anxiety and depression as well as improvement in functioning. Methods Participants (mean age = 43.3 years, SD = 13.2, 71.1% female, 55.5% white) were recruited from primary care centers throughout the United States and were randomized to receive either Coordinated Anxiety Learning and Management (CALM) treatment – composed of cognitive behavioral therapy, psychotropic medication, or both – or usual care. SE and OE ratings were collected at each session for participants in the CALM treatment (n = 482) and were entered into a structural equation model as predictors of changes in Brief Symptom Inventory, Anxiety Sensitivity Index, Patient Health Questionnaire (PHQ), and Sheehan Disability Scale outcomes at 6, 12, and 18 months after baseline. Results The best‐fitting models predict symptom levels from OE and SE and not vice versa. The slopes and intercept of OE significantly predicted change in each outcome variable except PHQ‐8. The slope and intercept of SE significantly predicted change in each outcome variable. Conclusion Over and above absolute level, increases in SE and OE were significant predictors of decreases in symptoms and increases in functioning. Implications for treatment are discussed, as well as future directions of research.

  March 11, 2014   doi: 10.1002/da.22256   open full text
• Lay Providers Can Deliver Effective Cognitive Behavior Therapy For Older Adults With Generalized Anxiety Disorder: A Randomized Trial.
  Melinda A. Stanley, Nancy L. Wilson, Amber B. Amspoker, Cynthia Kraus‐Schuman, Paula D. Wagener, Jessica S. Calleo, Jeffrey A. Cully, Ellen Teng, Howard M. Rhoades, Susan Williams, Nicholas Masozera, Matthew Horsfield, Mark E. Kunik.
  Depression and Anxiety. February 27, 2014
  Background The Institute of Medicine recommends developing a broader workforce of mental health providers, including nontraditional providers, to expand services for older adults. Cognitive behavior therapy (CBT) is effective for late‐life generalized anxiety disorder (GAD), but no study has examined outcomes with delivery by lay providers working under the supervision of licensed providers. The current study examined the effects of CBT delivered by lay, bachelor‐level providers (BLP) relative to Ph.D.‐level expert providers (PLP), and usual care (UC) in older adults with GAD. Methods Participants were 223 older adults (mean age, 66.9 years) with GAD recruited from primary care clinics at two sites and assigned randomly to BLP (n = 76), PLP (n = 74), or UC (n = 73). Assessments occurred at baseline and 6 months. CBT in BLP and PLP included core and elective modules (3 months: skills training; 3 months: skills review) delivered in person and by telephone, according to patient choice. Results CBT in both BLP and PLP groups significantly improved GAD severity (GAD Severity Scale), anxiety (Spielberger State‐Trait Anxiety Inventory; Structured Interview Guide for the Hamilton Anxiety Scale), depression (Patient Health Questionnaire), insomnia (Insomnia Severity Index), and mental health quality of life (Short‐Form‐12), relative to UC. Response rates defined by 20% reduction from pre‐ to posttreatment in at least three of four primary outcomes were higher for study completers in BLP and PLP relative to UC (BLP: 38.5%; PLP: 40.0%; UC: 19.1%). Conclusion Lay providers, working under the supervision of licensed providers, can deliver effective CBT.

  February 27, 2014   doi: 10.1002/da.22239   open full text
• Psychodynamic Psychotherapy Versus Cognitive Behavior Therapy For Social Anxiety Disorder: An Efficacy And Partial Effectiveness Trial.
  Susan M. Bögels, Paul Wijts, Frans J. Oort, Steph J. M. Sallaerts.
  Depression and Anxiety. February 27, 2014
  Objectives Comparing the overall and differential effects of psychodynamic psychotherapy (PDT) versus cognitive behavior therapy (CBT) for social anxiety disorder (SAD). Design Patients with a primary SAD (N = 47) were randomly assigned to PDT (N = 22) or CBT (N = 27). Both PDT and CBT consisted of up to 36 sessions (average PDT 31.4 and CBT 19.8 sessions). Assessments took place at waitlist: pretest, after 12 and 24 weeks for those who received longer treatment: posttest, 3‐month and 1‐year follow‐up. Methods Changes in the main outcome measure self‐reported social anxiety composite, as well as in other psychopathology, social skills, negative social beliefs, public self‐consciousness, defense mechanisms, personal goals, independent rater's judgments of SAD and general improvement, and approach behavior during an objective test, were analyzed using multilevel analysis. Results No improvement occurred during waitlist. Treatments were highly efficacious, with large within‐subject effect sizes for social anxiety, but no differences between PDT and CBT on general and treatment‐specific measures occurred. Remission rates were over 50% and similar for PDT and CBT. Personality disorders did not influence the effects of PDT or CBT. Conclusions PDT and CBT are both effective approaches for SAD. Further research is needed on the cost‐effectiveness of PDT versus CBT, on different lengths PDT, and on patient preferences and their relationship to outcome of PDT versus CBT.

  February 27, 2014   doi: 10.1002/da.22246   open full text
• Risk Factors For Anxiety Disorders: Common And Specific Effects In A National Sample.
  Carlos Blanco, José Rubio, Melanie Wall, Shuai Wang, Chelsea J. Jiu, Kenneth S. Kendler.
  Depression and Anxiety. February 27, 2014
  Background Anxiety disorders and major depressive disorder (MDD) often co‐occur and share a broad range of risk factors. The goal of this study was to examine whether the co‐occurrence of anxiety disorders and MDD could be explained by an underlying latent factor and whether the risk factors exert their effect exclusively through this factor, directly on each disorder, or through a combination of effects at both levels. Methods Data were drawn from a large, nationally representative sample. Confirmatory factor analysis was used to identify the latent structure of anxiety disorders. A multiple indicators multiple causes (MIMIC) approach was used to assess the common and specific effects of risk factors for anxiety disorders. Results A one‐factor model provided a good fit to the co‐occurrence of anxiety disorders. Low self‐esteem, family history of depression, female sex, childhood sexual abuse, White race, years of education, number of traumatic experiences, and disturbed family environment increased the risk of anxiety disorders and MDD through their effect on the latent factor. There were also several direct effects of the covariates on the disorders, indicating that the effect of the covariates differed across disorders. Conclusions Risk for anxiety disorders and MDD appears to be mediated partially by a latent variable underlying anxiety disorders and MDD, and partially by disorder‐specific effects. These findings may contribute to account for the high rates of comorbidity among disorders, identify commonalities in the etiologies of these disorders, and provide clues for the development of unified preventive interventions.

  February 27, 2014   doi: 10.1002/da.22247   open full text
• Comparing Family Accommodation In Pediatric Obsessive‐Compulsive Disorder, Anxiety Disorders, And Nonanxious Children.
  Eli R. Lebowitz, Lindsay A. Scharfstein, Johnna Jones.
  Depression and Anxiety. February 22, 2014
  Background Family accommodation describes ways in which parents modify their behavior to help a child avoid or alleviate distress caused by emotional disorders. Accommodation is associated with increased symptom severity, lower functioning, and poorer treatment outcomes. Accommodation is prevalent in childhood obsessive‐compulsive disorder (OCD) and anxiety disorders (ADs) but no studies have compared accommodation in these groups or compared them to healthy controls to ascertain if accommodation is prevalent in the general population. This study addresses these gaps by comparing patterns of accommodation, factors that maintain accommodation, and its relation to symptom severity in OCD and AD, relative to healthy controls. Method We directly compared reports of accommodation to childhood OCD (N = 26) and AD (N = 31), and a comparison group of nonanxious (NA) children (N = 30). Mothers completed measures of accommodation (Family Accommodation Scale (FAS)/Family Accommodation Scale–Anxiety (FASA)), anxiety (Screen for Childhood Anxiety Related Emotional Disorders–Parent Report (SCARED‐PR)), and OCD (Children's Yale‐Brown Obsessive Compulsive Scale (CYBOCS)). Results Family accommodation is prevalent among mothers of children with OCD and AD. Few differences were found between the two clinical groups who reported more accommodation (F[2,84] = 23.411, P < .001, partial η2 = .358), greater distress (F[2,84] = 24.050, P < .001, partial η2 = .364), and more consequences of not accommodating (F[2,84] = 18.967, P < .001, partial η2 = .311), than the NA group. Accommodation was associated with severity of anxiety in AD (r = .426, P = .017) and OCD (r = .465, P = .017), but not in the NA group. Conclusions Findings highlight family accommodation as a phenomenon that applies broadly and in a similar manner to children with AD and OCD. Evaluating accommodation provides useful information for clinical care and is an important part of the assessment of children with AD and OCD.

  February 22, 2014   doi: 10.1002/da.22251   open full text
• Focal And Aberrant Prefrontal Engagement During Emotion Regulation In Veterans With Posttraumatic Stress Disorder.
  Christine A. Rabinak, Annmarie MacNamara, Amy E. Kennedy, Mike Angstadt, Murray B. Stein, Israel Liberzon, K. Luan Phan.
  Depression and Anxiety. February 22, 2014
  Background Collectively, functional neuroimaging studies implicate frontal–limbic dysfunction in the pathophysiology of posttraumatic stress disorder (PTSD), as reflected by altered amygdala reactivity and deficient prefrontal responses. These neural patterns are often elicited by social signals of threat (fearful/angry faces) and traumatic reminders (combat sounds, script‐driven imagery). Although PTSD can be conceptualized as a disorder of emotion dysregulation, few studies to date have directly investigated the neural correlates of volitional attempts at regulating negative affect in PTSD. Methods Using functional magnetic resonance imaging and a well‐validated task involving cognitive regulation of negative affect via reappraisal and known to engage prefrontal cortical regions, the authors compared brain activation in veterans with PTSD (n = 21) and without PTSD (n = 21, combat‐exposed controls/CEC), following military combat trauma experience during deployments in Afghanistan or Iraq. The primary outcome measure was brain activation during cognitive reappraisal (i.e., decrease negative affect) as compared to passive viewing (i.e., maintain negative affect) of emotionally evocative content of aversive images Results The subjects in both groups reported similar successful reduction in negative affect following reappraisal. The PTSD group engaged the dorsolateral prefrontal cortex (dlPFC) during cognitive reappraisal, albeit to a lesser extent than the CEC group. Although the amygdala was engaged in both groups during passive viewing of aversive images, neither group exhibited attenuation of amygdala activation during cognitive reappraisal. Conclusions Veterans with combat‐related PTSD showed less recruitment of the dlPFC involved in cognitive reappraisal, suggesting focal and aberrant neural activation during volitional, self‐regulation of negative affective states.

  February 22, 2014   doi: 10.1002/da.22243   open full text
• An Investigation Of The Interactive Effects Of The Capability For Suicide And Acute Agitation On Suicidality In A Military Sample.
  Jessica D. Ribeiro, Theodore W. Bender, Jennifer M. Buchman, Matthew K. Nock, M. David Rudd, Craig J. Bryan, Ingrid C. Lim, Monty T. Baker, Chadwick Knight, Peter M. Gutierrez, Thomas E. Joiner.
  Depression and Anxiety. February 22, 2014
  Background According to the interpersonal theory of suicide (1, 2), the difficulties inherently associated with death by suicide deter many individuals from engaging in suicidal behavior. Consistent with the notion that suicide is fearsome, acute states of heightened arousal are commonly observed in individuals immediately prior to lethal and near‐lethal suicidal behavior. We suggest that among individuals who possess elevated levels of the capability for suicide, the heightened state of arousal experienced during periods of acute agitation may facilitate suicidal behavior in part because it would provide the necessary energy to approach a potentially lethal stimulus. Among individuals who are low on capability, the arousal experienced during agitation may result in further avoidance. Methods In the present project we examine how acute agitation may interact with the capability for suicide to predict suicidality in a large military sample (n = 1,208) using hierarchical multiple regression. Results Results were in line with a priori hypotheses: among individuals high on capability, as agitation increases, suicidality increases whereas as agitation increases among individuals low on capability, suicidality decreases. Results held beyond the effects of thwarted belongingness, perceived burdensomeness, and suicidal cognitions. Conclusions Beyond further substantiating the link between agitation and suicide, findings of the present study provide evidence for the construct validity of the acquired capability as well as offer initial evidence for moderating role of capability on the effect of agitation on suicide. Limitations of the current study highlight a need for future research that improves upon the techniques used in the present study. Implications for science and practice are discussed.

  February 22, 2014   doi: 10.1002/da.22240   open full text
• Oxytocin Promotes Protective Behavior In Depressed Mothers: A Pilot Study With The Enthusiastic Stranger Paradigm.
  Beth L. Mah, Marian J. Bakermans‐Kranenburg, Marinus H. IJzendoorn, Roger Smith.
  Depression and Anxiety. February 12, 2014
  Background Successful parenting requires maternal behaviors that promote infant survival such as protection from predators. In animal studies, oxytocin (OT) has been linked to maternal aggression to protect offspring. No human study has explored this topic. Mothers with a diagnosis of postnatal depression (PND) are at higher risk of neglecting their infants. We hypothesized that intranasal OT administration would increase the protective behaviors of mothers with PND, toward their infants. Methods Sixteen mothers with a diagnosis of PND participated in a double‐blind, randomized‐controlled, within‐subject pilot study. Participants received intranasal OT during one visit and placebo spray on the alternate visit. Maternal protective behavior toward their infant was measured, in the presence of a socially intrusive stranger. Results The enthusiastic stranger paradigm stimulated participants' protective responses in the presence of an intrusive stranger. Furthermore, this protective response of mothers with a diagnosis of PND was increased in the OT condition. Conclusions The study introduces a new paradigm, the enthusiastic stranger paradigm, which may be used to examine a neglected type of parental behavior, that is, protection of offspring. The protective response of mothers with PND increased, in line with the ‘tend and defend’ effects of OT in animal models. In future work it should be tested whether this protection effect can also be found in nonclinical samples, or whether it is specific for clinically depressed mothers.

  February 12, 2014   doi: 10.1002/da.22245   open full text
• Neuropsychological Performance Across Symptom Dimensions In Pediatric Obsessive Compulsive Disorder.
  Joseph F. McGuire, Erika A. Crawford, Jennifer M. Park, Eric A. Storch, Tanya K. Murphy, Michael J. Larson, Adam B. Lewin.
  Depression and Anxiety. February 12, 2014
  Background Few studies have examined neuropsychological functioning among youth with obsessive compulsive disorder (OCD), with inconclusive results. Although methodological differences may contribute to inconsistent findings, clinical factors may also account for differential performance. Symptom dimensions are associated with specific patterns of genetic transmission, comorbidity, and treatment outcome, and may also be uniquely associated with neuropsychological performance. This study examined differences in cognitive sequelae and neurocognitive impairment across symptom dimensions among youth with OCD. Method Participants included 93 treatment‐seeking youth diagnosed with OCD. A trained clinician administered the Children's Yale‐Brown Obsessive Compulsive Scale (CY‐BOCS) to parents and children together. Afterward, youth completed a battery of neuropsychological tests that assessed nonverbal memory and fluency, verbal memory, verbal fluency, verbal learning, processing speed, and inhibition/switching. Results Across five symptom dimensions, youth exhibiting Hoarding symptoms (χ2 = 5.21, P = .02) and Symmetry/Ordering symptoms had a greater occurrence of cognitive sequelae (χ2 = 4.86, P = .03). Additionally, youth with Symmetry/Ordering symptoms had a greater magnitude of cognitive impairment (Mann–Whitney U = 442.50, Z = –2.49, P < .02), with specific deficits identified on nonverbal fluency (P < .01), processing speed (P < .01), and inhibition and switching (P < .02). Conclusions Neuropsychological deficits identified in youth with Hoarding and Symmetry/Ordering symptoms may suggest that these symptoms have characteristics specific to neurocognitive impairment. Alternatively, symptoms associated with these dimensions may impede youth's performance during testing. Findings advise neuropsychological testing for youth with symptoms on either of these dimensions when concerns about neuropsychological and/or academic impairment are present.

  February 12, 2014   doi: 10.1002/da.22241   open full text
• Six‐Month Postintervention Depression And Disability Outcomes Of In‐Home Telehealth Problem‐Solving Therapy For Depressed, Low‐Income Homebound Older Adults.
  Namkee G. Choi, C. Nathan Marti, Martha L. Bruce, Mark T. Hegel, Nancy L. Wilson, Mark E. Kunik.
  Depression and Anxiety. February 05, 2014
  Background Despite their high rates of depression, homebound older adults have limited access to evidence‐based psychotherapy. The purpose of this paper was to report both depression and disability outcomes of telehealth problem‐solving therapy (tele‐PST via Skype video call) for low‐income homebound older adults over 6 months postintervention. Methods A 3‐arm randomized controlled trial compared the efficacy of tele‐PST to in‐person PST and telephone care calls with 158 homebound individuals who were aged 50+ and scored 15+ on the 24‐item Hamilton Rating Scale for Depression (HAMD). Treatment effects on depression severity (HAMD score) and disability (score on the WHO Disability Assessment Schedule [WHODAS]) were analyzed using mixed‐effects regression with random intercept models. Possible reciprocal relationships between depression and disability were examined with a parallel‐process latent growth curve model. Results Both tele‐PST and in‐person PST were efficacious treatments for low‐income homebound older adults; however the effects of tele‐PST on both depression and disability outcomes were sustained significantly longer than those of in‐person PST. Effect sizes (dGMA‐raw) for HAMD score changes at 36 weeks were 0.68 for tele‐PST and 0.20 for in‐person PST. Effect sizes for WHODAS score changes at 36 weeks were 0.47 for tele‐PST and 0.25 for in‐person PST. The results also supported reciprocal and indirect effects between depression and disability outcomes. Conclusions The efficacy and potential low cost of tele‐delivered psychotherapy show its potential for easy replication and sustainability to reach a large number of underserved older adults and improve their access to mental health services.

  February 05, 2014   doi: 10.1002/da.22242   open full text
• Challenging The Myth Of An “Epidemic” Of Common Mental Disorders: Trends In The Global Prevalence Of Anxiety And Depression Between 1990 And 2010.
  Amanda J. Baxter, Kate M. Scott, Alize J. Ferrari, Rosana E. Norman, Theo Vos, Harvey A. Whiteford.
  Depression and Anxiety. January 21, 2014
  Background Anxiety disorders and major depressive disorder (MDD) are common and disabling mental disorders. This paper aims to test the hypothesis that common mental disorders have become more prevalent over the past two decades. Methods We conducted a systematic review of prevalence, remission, duration, and excess mortality studies for anxiety disorders and MDD and then used a Bayesian meta‐regression approach to estimate point prevalence for 1990, 2005, and 2010. We also conducted a post‐hoc search for studies that used the General Health Questionnaire (GHQ) as a measure of psychological distress and tested for trends to present a qualitative comparison of study findings Results This study found no evidence for an increased prevalence of anxiety disorders or MDD. While the crude number of cases increased by 36%, this was explained by population growth and changing age structures. Point prevalence of anxiety disorders was estimated at 3.8% (3.6–4.1%) in 1990 and 4.0% (3.7–4.2%) in 2010. The prevalence of MDD was unchanged at 4.4% in 1990 (4.2–4.7%) and 2010 (4.1–4.7%). However, 8 of the 11 GHQ studies found a significant increase in psychological distress over time. Conclusions The perceived “epidemic” of common mental disorders is most likely explained by the increasing numbers of affected patients driven by increasing population sizes. Additional factors that may explain this perception include the higher rates of psychological distress as measured using symptom checklists, greater public awareness, and the use of terms such as anxiety and depression in a context where they do not represent clinical disorders.

  January 21, 2014   doi: 10.1002/da.22230   open full text
• Efficacy And Acceptability Of Acute Treatments For Persistent Depressive Disorder: A Network Meta‐Analysis.
  Levente Kriston, Alessa Wolff, Annika Westphal, Lars P. Hölzel, Martin Härter.
  Depression and Anxiety. January 21, 2014
  Background We aimed to synthesize the available evidence on the relative efficacy and acceptability of specific treatments for persistent depressive disorder. Methods We searched several databases up to January 2013 and included randomized controlled trials that compared acute pharmacological, psychotherapeutic, and combined interventions with each other or placebo. The outcome measures were the proportion of patients who responded to (efficacy) or dropped out from (acceptability) the allocated treatment. Data synthesis was performed with network meta‐analysis. Results A network of 45 trials that tested 28 drugs included data from 5,806 and 5,348 patients concerning efficacy and acceptability, respectively. A second network of 15 trials that tested five psychotherapeutic and five combined interventions included data from 2,657 and 2,719 patients concerning efficacy and acceptability, respectively. Among sufficiently tested treatments, fluoxetine (odds ratio (OR) 2.94), paroxetine (3.79), sertraline (4.47), moclobemide (6.98), imipramine (4.53), ritanserin (2.35), amisulpride (5.63), and acetyl‐l‐carnitine (5.67) were significantly more effective than placebo. Pairwise comparisons showed advantages of moclobemide (2.38) and amisulpride (1.92) over fluoxetine. Sertraline (0.57) and amisulpride (0.53) showed a lower dropout rate than imipramine. Interpersonal psychotherapy with medication outperformed medication alone in chronic major depression but not in dysthymia. Evidence on cognitive behavioral analysis system of psychotherapy plus medication was partly inconclusive. Interpersonal psychotherapy was less effective than medication (0.48) and cognitive behavioral analysis system of psychotherapy (0.45). Several other treatments were tested in single studies. Conclusions Several evidence‐based acute pharmacological, psychotherapeutic, and combined treatments for persistent depressive disorder are available with significant differences between them.

  January 21, 2014   doi: 10.1002/da.22236   open full text
• Major Depressive Disorder Subtypes To Predict Long‐Term Course.
  Hanna M. Loo, Tianxi Cai, Michael J. Gruber, Junlong Li, Peter Jonge, Maria Petukhova, Sherri Rose, Nancy A. Sampson, Robert A. Schoevers, Klaas J. Wardenaar, Marsha A. Wilcox, Ali Obaid Al‐Hamzawi, Laura Helena Andrade, Evelyn J. Bromet, Brendan Bunting, John Fayyad, Silvia E. Florescu, Oye Gureje, Chiyi Hu, Yueqin Huang, Daphna Levinson, Maria Elena Medina‐Mora, Yoshibumi Nakane, Jose Posada‐Villa, Kate M. Scott, Miguel Xavier, Zahari Zarkov, Ronald C. Kessler.
  Depression and Anxiety. January 14, 2014
  Background Variation in the course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here. Methods Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs), followed by k‐means cluster analysis are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM‐IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode, number of years with an episode lasting most of the year) and severity (hospitalization for MDD, disability due to MDD). Results Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness–worry–anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high‐risk cluster (30.0% of respondents) accounted for 52.9–69.7% of high persistence and severity, and it was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor. Conclusions Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data.

  January 14, 2014   doi: 10.1002/da.22233   open full text
• Early‐Life Predictors Of Internalizing Symptom Trajectories In Canadian Children.
  Murray Weeks, John Cairney, T. Cameron Wild, George B. Ploubidis, Kiyuri Naicker, Ian Colman.
  Depression and Anxiety. January 14, 2014
  Background Previous research examining the development of anxious and depressive symptoms (i.e., internalizing symptoms) from childhood to adolescence has often assumed that trajectories of these symptoms do not vary across individuals. The purpose of this study was to identify distinct trajectories of internalizing symptoms from childhood to adolescence, and to identify risk factors for membership in these trajectory groups. In particular, we sought to identify risk factors associated with early appearing (i.e., child onset) symptoms versus symptoms that increase in adolescence (i.e., adolescent onset). Method Drawing on longitudinal data from the National Longitudinal Survey of Children and Youth, latent class growth modeling (LCGM) was used to identify distinct trajectories of internalizing symptoms for 6,337 individuals, from age 4–5 to 14–15. Multinomial regression was used to examine potential early‐life risk factors for membership in a particular trajectory group. Results Five trajectories were identified as follows: “low stable” (68%; reference group), “adolescent onset” (10%), “moderate stable” (12%), “high childhood” (6%), and “high stable” (4%). Membership in the “adolescent onset” group was predicted by child gender (greater odds for girls), stressful life events, hostile parenting, aggression, and hyperactivity. Membership in the “high stable” and “high childhood” trajectory groups (i.e., child‐onset) was additionally predicted by maternal depression, family dysfunction, and difficult temperament. Also, several significant gender interactions were observed. Conclusions Causal mechanisms for child and adolescent depression and anxiety may differ according to time of onset, as well as child gender. Some early factors may put girls at greater risk for internalizing problems than boys.

  January 14, 2014   doi: 10.1002/da.22235   open full text
• Obsessive–Compulsive Disorder And Female Reproductive Cycle Events: Results From The Ocd And Reproduction Collaborative Study.
  Valeria Guglielmi, Nienke C. C. Vulink, Damiaan Denys, Ying Wang, Jack F. Samuels, Gerald Nestadt.
  Depression and Anxiety. January 13, 2014
  Background Women with obsessive–compulsive disorder (OCD) often report that symptoms first appear or exacerbate during reproductive cycle events; however, little is known about these relationships. The goals of this study were to examine, in a US and a European female OCD sample, onset and exacerbation of OCD in reproductive cycle events, and to investigate the likelihood of repeat exacerbation in subsequent pregnancies and postpartum periods. Methods Five hundred forty‐two women (United States, n = 352; Dutch, n = 190) who met DSM‐IV criteria for OCD, completed self‐report questionnaires designed to assess OCD onset and symptom exacerbation associated with reproductive events. Results OCD onset occurred within 12 months after menarche in 13.0%, during pregnancy in 5.1%, at postpartum in 4.7%, and at menopause in 3.7%. Worsening of pre‐existing OCD was reported by 37.6% of women at premenstruum, 33.0% during pregnancy, 46.6% postpartum, and 32.7% at menopause. Exacerbation in first pregnancy was significantly associated with exacerbation in second pregnancy (OR = 10.82, 95% CI 4.48–26.16), as was exacerbation in first postpartum with exacerbation in second postpartum (OR = 6.86, 95% CI 3.27–14.36). Results were replicated in both samples. Conclusions Reproductive cycle events are periods of increased risk for onset and exacerbation of OCD in women. The present study is the first to provide significant evidence that exacerbation in or after first pregnancy is a substantial risk factor for exacerbation in or after a subsequent pregnancy. Further research is needed to identify factors related to exacerbation, so that physicians may provide appropriate recommendations to women regarding clinical issues involving OCD and reproductive cycle events.

  January 13, 2014   doi: 10.1002/da.22234   open full text
• Data‐Driven Course Trajectories In Primary Care Patients With Major Depressive Disorder.
  Klaas J. Wardenaar, Henk‐Jan Conradi, Peter Jonge.
  Depression and Anxiety. January 03, 2014
  Background The chronic nature of MDD has been acknowledged as one of the key determinants of the burden associated with depression. Unfortunately, so far described prognostic factors have been inconsistent, possibly due to used course outcomes that are often based on arbitrary criteria/cut‐offs. Therefore, the aim of the current study was to use data‐driven trajectory groups based on closely spaced weekly severity ratings, as outcomes in prognostic research. Methods The sample consisted of primary care patients with MDD (n = 153), who were followed up for a year with 52 consecutive weekly ratings of the nine DSM‐IV MDD criterion symptoms. Growth Mixture Modeling (GMM) was used to reduce the interpersonal growth variation to an optimal set of clinically interpretable trajectory groups. Next, baseline course predictors were investigated and the prognostic (added) value of course‐group membership was investigated for clinical outcomes after 1, 2, and 3 years. Results GMM resulted in four trajectory groups: “early remission” (40.2%), “late remission” (9.8%), “remission and recurrence” (17.0%), and “chronic” (33.0%). Multivariate predictors of “chronic” group membership were a prior suicide attempt, comorbid dysthymia, and lower levels of somatic depressive symptoms. Group membership predicted differences in depression severity and/or quality of life after 1, 2, and 3 years. Conclusions The used data‐driven approach provided a parsimonious and clinically informative way to describe course variation across MDD patients. Using the trajectory groups to investigate prognostic factors of MDD provided insight in potentially useful prognostic factors. Importantly, trajectory‐group membership was itself a strong predictor of future mental well‐being.

  January 03, 2014   doi: 10.1002/da.22228   open full text
• Gender‐Specific Association Of Variants In The Akr1 C1 Gene With Dimensional Anxiety In Patients With Panic Disorder: Additional Evidence For The Importance Of Neurosteroids In Anxiety?
  Carina Quast, Andreas Reif, Tanja Brückl, Hildegard Pfister, Heike Weber, Manuel Mattheisen, Sven Cichon, Thomas Lang, Alfons Hamm, Lydia Fehm, Andreas Ströhle, Volker Arolt, Katharina Domschke, Tilo Kircher, Hans‐Ulrich Wittchen, Paul Pauli, Alexander L. Gerlach, Georg W. Alpers, Jürgen Deckert, Rainer Rupprecht, Elisabeth B. Binder, Angelika Erhardt.
  Depression and Anxiety. January 03, 2014
  Background Neurosteroids are synthesized both in brain and peripheral steroidogenic tissue from cholesterol or steroidal precursors. Neurosteroids have been shown to be implicated in neural proliferation, differentiation, and activity. Preclinical and clinical studies also suggest a modulatory role of neurosteroids in anxiety‐related phenotypes. However, little is known about the contribution of genetic variants in genes relevant for the neurosteroidogenesis to anxiety disorders. Methods We performed an association analysis of single nucleotide polymorphisms (SNPs) in five genes related to the neurosteroidal pathway with emphasis on progesterone and allopregnanolone biosynthesis (steroid‐5‐alpha‐reductase 1A (SRD5A1), aldo‐keto reductase family 1 C1‐C3 (AKR1C1‐AKR1C3) and translocator protein 18 kDA (TSPO) with panic disorder (PD) and dimensional anxiety in two German PD samples (cases N = 522, controls N = 1,115). Results Case–control analysis for PD and SNPs in the five selected genes was negative in the combined sample. However, we detected a significant association of anticipatory anxiety with two intronic SNPs (rs3930965, rs41314625) located in the gene AKR1C1 surviving correction for multiple testing in PD patients. Stratification analysis for gender revealed a female‐specific effect of the associations of both SNPs. Conclusions These results suggest a modulatory effect of AKR1C1 activity on anxiety levels, most likely through changes in progesterone and allopregnanolone levels within and outside the brain. In summary, this is the first evidence for the gender‐specific implication of the AKR1C1 gene in the expression of anticipatory anxiety in PD. Further analyses to unravel the functional role of the SNPs detected here and replication analyses are needed to validate our results.

  January 03, 2014   doi: 10.1002/da.22229   open full text
• Primum Non Nocere (First Do No Harm): Symptom Worsening And Improvement In Female Assault Victims After Prolonged Exposure For Ptsd.
  Nuwan Jayawickreme, Shawn P. Cahill, David S. Riggs, Sheila A. M. Rauch, Patricia A. Resick, Barbara O. Rothbaum, Edna B. Foa.
  Depression and Anxiety. December 30, 2013
  Background Prolonged Exposure (PE) therapy is an efficacious treatment for PTSD; despite this, many clinicians do not utilize it due to concerns it could cause patient decompensation. Method Data were pooled from four published well‐controlled studies of female assault survivors with chronic PTSD (n = 361) who were randomly assigned to PE, waitlist (WL), or another psychotherapy, including cognitive processing therapy (CPT), Eye Movement and Desensitization Reprocessing (EMDR), or the combination of PE plus stress inoculation training (SIT) or PE plus cognitive restructuring. PTSD and depression severity scores were converted to categorical outcomes to evaluate the proportion of participants who showed reliable symptom change (both reliable worsening and reliable improvement). Results The majority of participants completing one of the active treatments showed reliable improvement on both PTSD and depression compared to WL. Among treatment participants in general, as well as those who received PE, reliable PTSD worsening was nonexistent and the rate of reliable worsening of depression was low. There were no differences on any outcome measures among treatments. By comparison, participants in WL had higher rates of reliable symptom worsening for both PTSD and depression. Potential alternative explanations were also evaluated. Conclusions PE and a number of other empirically supported therapies are efficacious and safe treatments for PTSD, reducing the frequency of which symptom worsening occurs in the absence of treatment.

  December 30, 2013   doi: 10.1002/da.22225   open full text
• The Effect Of Gender, Age, And Symptom Severity In Late‐Life Depression On The Risk Of All‐Cause Mortality: The Bambuí Cohort Study Of Aging.
  Breno S. Diniz, Charles F. Reynolds, Meryl A. Butters, Mary Amanda Dew, Josélia O. A. Firmo, Maria Fernanda Lima‐Costa, Erico Castro‐Costa.
  Depression and Anxiety. December 18, 2013
  Background Increased mortality risk and its moderators is an important, but still under recognized, negative outcome of late‐life depression (LLD). Therefore, we aimed to evaluate whether LLD is a risk factor for all‐cause mortality in a population‐based study with over 10 years of follow‐up, and addressed the moderating effect of gender and symptom severity on mortality risk. Methods This analysis used data from the Bambuí Cohort Study of Aging. The study population comprised 1.508 (86.5%) of all eligible 1.742 elderly residents. Depressive symptoms were annually evaluated by the GHQ‐12, with scores of five or higher indicating clinically significant depression. From 1997 to 2007, 441 participants died during 10,648 person‐years of follow‐up. We estimated the hazard ratio for mortality risk by Cox regression analyses. Results Depressive symptoms were a risk factor for all‐cause mortality after adjusting for confounding lifestyle and clinical factors (adjusted HR = 1.24 CI95% [1.00–1.55], P = .05). Mortality risk was significantly elevated in men (adjusted HR = 1.45 CI95% [1.01–2.07], P = 0.04), but not in women (adjusted HR = 1.13 CI95% [0.84–1.48], P = 0.15). We observed a significant interaction between gender and depressive symptoms on mortality risk ((HR = 1.72 CI95% [1.18–2.49], P = 0.004). Conclusion The present study provides evidence that LLD is a risk factor for all‐cause mortality in the elderly, especially in men. The prevention and adequate treatment of LLD may help to reduce premature disability and death among elders with depressive symptoms.

  December 18, 2013   doi: 10.1002/da.22226   open full text
• Perceived Social Support Mediates Anxiety And Depressive Symptom Changes Following Primary Care Intervention.
  Halina J. Dour, Joshua F. Wiley, Peter Roy‐Byrne, Murray B. Stein, Greer Sullivan, Cathy D. Sherbourne, Alexander Bystritsky, Raphael D. Rose, Michelle G. Craske.
  Depression and Anxiety. December 12, 2013
  Background The current study tested whether perceived social support serves as a mediator of anxiety and depressive symptom change following evidence‐based anxiety treatment in the primary care setting. Gender, age, and race were tested as moderators. Methods Data were obtained from 1004 adult patients (age M = 43, SD = 13; 71% female; 56% White, 20% Hispanic, 12% Black) who participated in a randomized effectiveness trial (coordinated anxiety learning and management [CALM] study) comparing evidence‐based intervention (cognitive‐behavioral therapy and/or psychopharmacology) to usual care in the primary care setting. Patients were assessed with a battery of questionnaires at baseline, as well as at 6, 12, and 18 months following baseline. Measures utilized in the mediation analyses included the Abbreviated Medical Outcomes (MOS) Social Support Survey, the Brief Symptom Index (BSI)–Somatic and Anxiety subscales, and the Patient Health Questionnaire (PHQ‐9). Results There was a mediating effect over time of perceived social support on symptom change following treatment, with stronger effects for 18‐month depression than anxiety. None of the mediating pathways were moderated by gender, age, or race. Conclusions Perceived social support may be central to anxiety and depressive symptom changes over time with evidence‐based intervention in the primary care setting. These findings possibly have important implications for development of anxiety interventions.

  December 12, 2013   doi: 10.1002/da.22216   open full text
• Functional Polymorphism In The Brain‐Derived Neurotrophic Factor Gene Interacts With Stressful Life Events But Not Childhood Maltreatment In The Etiology Of Depression.
  George W. Brown, Thomas K. J. Craig, Tirril O. Harris, Joe Herbert, Karen Hodgson, Katherine E. Tansey, Rudolf Uher.
  Depression and Anxiety. December 12, 2013
  Background We test the hypothesis that the functional Val66Met polymorphism of BDNF interacts with recent life events to produce onset of new depressive episodes. We also explore the possibility that the Met allele of this polymorphism interacts with childhood maltreatment to increase the risk of chronic depression. Methods In a risk‐enriched combined sample of unrelated women, childhood maltreatment and current life events were measured with the Childhood Experience of Care and Abuse, and Life Events and Difficulties Schedule interviews. Chronic episodes of depression (12 months or longer) during adulthood and onset of a major depressive episode during a 12‐month follow‐up were established with the Schedules for Clinical Assessment in Neuropsychiatry interview. Results Met alleles of BDNF moderated the relationship between recent life events and adult onsets of depression in a significant gene–environment interaction (interaction risk difference 0.216, 95% CI 0.090–0.342; P =.0008). BDNF did not significantly influence the effect of childhood maltreatment on chronic depression in the present sample. Conclusions The Met allele of BDNF increases the risk of a new depressive episode following a severe life event. The BDNF and the serotonin transporter gene length polymorphism (5‐HTTLPR) and BDNF may contribute to depression through distinct mechanisms involving interactions with childhood and adulthood adversity respectively, which may, in combination, be responsible for a substantial proportion of depression burden in the general population.

  December 12, 2013   doi: 10.1002/da.22221   open full text
• Glucocorticoids Enhance In Vivo Exposure‐Based Therapy Of Spider Phobia.
  Leila M. Soravia, Markus Heinrichs, Livia Winzeler, Melanie Fisler, Wolfgang Schmitt, Helge Horn, Thomas Dierks, Werner Strik, Stefan G. Hofmann, Dominique J.‐F. Quervain.
  Depression and Anxiety. November 21, 2013
  Background Preclinical and clinical studies indicate that the administration of glucocorticoids may promote fear extinction processes. In particular, it has been shown that glucocorticoids enhance virtual reality based exposure therapy of fear of heights. Here, we investigate whether glucocorticoids enhance the outcome of in vivo exposure‐based group therapy of spider phobia. Methods In a double blind, block‐randomized, placebo‐controlled, between‐subject study design, 22 patients with specific phobia of spiders were treated with two sessions of in vivo exposure‐based group therapy. Cortisol (20 mg) or placebo was orally administered 1 hr before each therapy session. Patients returned for a follow‐up assessment one month after therapy. Results Exposure‐based group therapy led to a significant decrease in phobic symptoms as assessed with the Fear of Spiders Questionnaire (FSQ) from pretreatment to immediate posttreatment and to follow‐up. The administration of cortisol to exposure therapy resulted in increased salivary cortisol concentrations and a significantly greater reduction in fear of spiders (FSQ) as compared to placebo at follow‐up, but not immediately posttreatment. Furthermore, cortisol‐treated patients reported significantly less anxiety during standardized exposure to living spiders at follow‐up than placebo‐treated subjects. Notably, groups did not differ in phobia‐unrelated state‐anxiety before and after the exposure sessions and at follow‐up. Conclusions These findings indicate that adding cortisol to in vivo exposure‐based group therapy of spider phobia enhances treatment outcome.

  November 21, 2013   doi: 10.1002/da.22219   open full text
• Development And Validation Of A Prediction Algorithm For Use By Health Professionals In Prediction Of Recurrence Of Major Depression.
  Jian Li Wang, Scott Patten, Jitender Sareen, James Bolton, Norbert Schmitz, Glenda MacQueen.
  Depression and Anxiety. November 13, 2013
  Background There exists very little evidence to guide clinical management for preventing recurrence of major depression. The objective of this study was to develop and validate a prediction algorithm for recurrence of major depression. Methods Wave 1 and wave 2 longitudinal data from the U.S. National Epidemiological Survey on Alcohol and Related Condition (2001/2002–2003/2004) were used. Participants with a major depressive episode at baseline and who had visited health professionals for depression were included in this analysis (n = 2,711). Mental disorders were assessed based on the DSM‐IV criteria. Results With the development data (n = 1,518), a prediction model with 19 unique factors had a C statistics of 0.7504 and excellent calibration (P = .23). The model had a C statistics of 0.7195 in external validation data (n = 1,195) and 0.7365 in combined data. The algorithm calibrated very well in validation data. In the combined data, the 3‐year observed and predicted risk of recurrence was 25.40% (95% CI: 23.76%, 27.04%) and 25.34% (95% CI: 24.73%, 25.95%), respectively. The predicted risk in the 1st and 10th decile risk group was 5.68% and 60.21%, respectively. Conclusions The developed prediction model for recurrence of major depression has acceptable discrimination and excellent calibration, and is feasible to be used by physicians. The prognostic model may assist physicians and patients in quantifying the probability of recurrence so that physicians can develop specific treatment plans for those who are at high risk of recurrence, leading to personalized treatment and better use of resources.

  November 13, 2013   doi: 10.1002/da.22215   open full text
• N2 And P3 Potentials In Early‐Onset And Late‐Onset Patients With Obsessive‐Compulsive Disorder.
  Yasemin Keskin‐Ergen, Raşit Tükel, Banu Aslantaş‐Ertekin, Erhan Ertekin, Serap Oflaz, Müge Devrim‐Üçok.
  Depression and Anxiety. November 10, 2013
  Background Impaired cognitive control processes may be central in the pathogenesis of obsessive‐compulsive disorder (OCD). Our objective was to evaluate cognitive control processes with event‐related potentials in early‐onset OCD (EO) and late‐onset OCD (LO), which are suggested to have distinct characteristics. Methods Participants were unmedicated EO (n = 26) and LO patients (n = 33) without comorbid psychopathology and healthy controls (n = 54). Go/No‐go tasks with 50 and 80% Go trial probabilities were implemented to manipulate the strength of response conflict and inhibitory demands. Results LO patients had shorter N2 latencies than controls and did not show the N2 amplitude increase seen in controls with the increase in Go trial probability as suggestive of abnormal conflict monitoring processes. Both EO and LO patients showed smaller P3 increase than controls with the increase in Go trial probability, suggesting problems in modifying attentional control with changes in task demands. P3 was more anteriorly distributed in LO patients than controls. Additionally, P3 increase, with the increase in Go trial probability, was larger in frontal and central sites than in parietal sites in controls, whereas in EO patients it was almost homogenous across anteroposterior sites. Conclusions N2 processes were affected only in LO, whereas P3 processes were affected in both EO and LO, although, somewhat differently. P3 distributions suggest that EO and LO patients have differences concerning the contributions of frontal and parietal components of attentional networks to the execution of Go/No‐go tasks. Our results imply that EO and LO are distinct subtypes affecting the cognitive control systems differently.

  November 10, 2013   doi: 10.1002/da.22212   open full text
• Interpretation And Expectations Among Mothers Of Children With Anxiety Disorders: Associations With Maternal Anxiety Disorder.
  Faith Orchard, Peter J. Cooper, Cathy Creswell.
  Depression and Anxiety. November 10, 2013
  Background Models of the development and maintenance of childhood anxiety suggest an important role for parent cognitions: that is, negative expectations of children's coping abilities lead to parenting behaviors that maintain child anxiety. The primary aims of the current study were to (1) compare expectations of child vulnerability and coping among mothers of children with anxiety disorders on the basis of whether or not mothers also had a current anxiety disorder, and (2) examine the degree to which the association between maternal anxiety disorder status and child coping expectations was mediated by how mothers interpreted ambiguous material that referred to their own experience. Methods The association between interpretations of threat, negative emotion, and control was assessed using hypothetical ambiguous scenarios in a sample of 271 anxious and nonanxious mothers of 7‐ to 12‐year‐old children with an anxiety disorder. Mothers also rated their expectations when presented with real life challenge tasks. Results There was a significant association between maternal anxiety disorder status and negative expectations of child coping behaviors. Mothers’ self‐referent interpretations were found to mediate this relationship. Responses to ambiguous hypothetical scenarios correlated significantly with responses to real life challenge tasks. Conclusions Treatments for childhood anxiety disorders in the context of parental anxiety disorders may benefit from the inclusion of a component to directly address parental cognitions. Some inconsistencies were found when comparing maternal expectations in response to hypothetical scenarios with real life challenges. This should be addressed in future research.

  November 10, 2013   doi: 10.1002/da.22211   open full text
• Adequacy Of Treatment Received By Primary Care Patients With Anxiety Disorders.
  Risa B. Weisberg, Courtney Beard, Ethan Moitra, Ingrid Dyck, Martin B. Keller.
  Depression and Anxiety. November 04, 2013
  Background We examined the adequacy of pharmacotherapy and psychotherapy received by primary care patients with anxiety disorders over up to 5 years of follow‐up. Method Five hundred thirty‐four primary care patients at 15 US sites, who screened positive for anxiety symptoms, were assessed for anxiety disorders. Those meeting anxiety disorder criteria were offered participation and interviewed again at six and 12 months postintake, and yearly thereafter for up to 5 years. We utilized existing definitions of appropriate pharmacotherapy and created definitions of potentially adequate psychotherapy/cognitive‐behavioral therapy (CBT). Results At intake, of 534 primary care participants with anxiety disorders, 19% reported receiving appropriate pharmacotherapy and 14% potentially adequate CBT. Overall, 28% of participants reported receiving potentially adequate anxiety treatment, whether pharmacotherapy, psychotherapy, or both. Over up to five years of follow‐up, appropriate pharmacotherapy was received by 60% and potentially adequate CBT by 36% of the sample. Examined together, 69% of participants received any potentially adequate treatment during the follow‐up period. Over the course of follow‐up, primary care patients with MDD, panic disorder with agoraphobia, and with medicaid/medicare were more likely to receive appropriate anxiety treatment. Ethnic minority members were less likely to receive potentially adequate care. Conclusions Potentially adequate anxiety treatment was rarely received by primary care patients with anxiety disorders at intake. Encouragingly, rates improved over the course of the study. However, potentially adequate CBT remained much less utilized than pharmacotherapy and racial‐ethnic minority members were less likely to received care, suggesting much room for improved dissemination of quality treatment.

  November 04, 2013   doi: 10.1002/da.22209   open full text
• Exercise Improves Sexual Function In Women Taking Antidepressants: Results From A Randomized Crossover Trial.
  Tierney Ahrold Lorenz, Cindy May Meston.
  Depression and Anxiety. November 01, 2013
  Background In laboratory studies, exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [1]. We evaluated if exercise improves sexual desire, orgasm, and global sexual functioning in women experiencing antidepressant‐induced sexual side effects. Methods Fifty‐two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only. They were randomized to complete either three weeks of exercise immediately before sexual activity (3×/week) or 3 weeks of exercise separate from sexual activity (3×/week). At the end of the first exercise arm, participants crossed to the other. We measured sexual functioning, sexual satisfaction, depression, and physical health. Results Exercise immediately prior to sexual activity significantly improved sexual desire and, for women with sexual dysfunction at baseline, global sexual function. Scheduling regular sexual activity significantly improved orgasm function; exercise did not increase this benefit. Neither regular sexual activity nor exercise significantly changed sexual satisfaction. Conclusions Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants.

  November 01, 2013   doi: 10.1002/da.22208   open full text
• Maternal Depressive, Anxious, And Stress Symptoms During Pregnancy Predict Internalizing Problems In Adolescence.
  Kim S. Betts, Gail M. Williams, Jacob M. Najman, Rosa Alati.
  Depression and Anxiety. October 31, 2013
  Background Studies have shown a link between maternal–prenatal mental health and offspring behavior problems. In this paper, we derived longitudinal trajectories of maternal depressive, anxious, and stress symptoms over early life to predict offspring behavior in adolescence. Methods Participants included 3,925 mother–offspring pairs from the Mater University Study of Pregnancy (MUSP), an Australian‐based, prebirth cohort study. Latent class growth analysis with parallel processes was used to identify trajectories of maternal depressive, anxious, and stress symptoms over four measurement periods between the mothers’ first clinic visit and 5 years postpregnancy. The estimates from the maternal trajectories were used to fit multivariate logistic regression models and predict internalizing and externalizing behavior at age 14. We adjusted for a wide range of factors, including a number of prenatal confounders, concurrent maternal depressive and anxious symptoms, father's history of mental problems, and maternal life events relationship quality and contact with the new born. Results Seven maternal trajectories were identified one of which isolated high levels of depressive, anxious, and stress symptoms during pregnancy. After adjustment for confounders, this was the only trajectory that predicted higher internalizing behavior in adolescence. No specific maternal trajectory predicted externalizing problems. Conclusions We found evidence for a prenatal effect, whereby high levels of maternal depression, anxiety, and stress symptoms in early pregnancy uniquely increased the risk of internalizing behavior problems in adolescence.

  October 31, 2013   doi: 10.1002/da.22210   open full text
• Predictors Of Completion Of Exposure Therapy In Oef/Oif Veterans With Posttraumatic Stress Disorder.
  Daniel F. Gros, Matthew Price, Erica K. Yuen, Ron Acierno.
  Depression and Anxiety. October 21, 2013
  Background Despite large‐scale dissemination and implementation efforts of evidence‐based psychotherapy to veterans from Operation Enduring/Iraqi Freedom (OEF/OIF), little is known regarding the factors that contribute to the successful completion of these treatments in this high‐risk population. The present study investigated predictors of treatment completion during a standardized exposure‐based psychotherapy for PTSD. Methods Ninety‐two OEF/OIF combat veterans enrolled in a randomized controlled trial for an eight session exposure‐based psychotherapy for PTSD. All participants completed structured clinical interviews and several background and symptom questionnaires. Of the initial 92 participants, 28% of the sample (n = 26) discontinued treatment prior to completion of the trial. Results Predictors of discontinuation of treatment were assessed with a hierarchical logistic regression. Disability status was positively associated with treatment discontinuation, and postdeployment social support was negatively associated with discontinuation. In contrast to previous findings, other factors, such as age and PTSD symptomatology, were not identified as significant predictors. Conclusions The present study suggested that disability status at the start of treatment increases the risk for treatment discontinuation whereas increased social support buffers against discontinuation. Together, these findings highlight the importance of increased assessment and early intervention when these factors are present to potentially reduce treatment discontinuation and improve treatment outcomes in OEF/OIF veterans with PTSD.

  October 21, 2013   doi: 10.1002/da.22207   open full text
• Emotion Regulation Predicts Anxiety Over A Five‐Year Interval: A Cross‐Lagged Panel Analysis.
  Carolin M. Wirtz, Stefan G. Hofmann, Heleen Riper, Matthias Berking.
  Depression and Anxiety. October 21, 2013
  Background Emotion regulation (ER) deficits have been linked to symptoms of anxiety in cross‐sectional studies. However, the direction of the relationship between ER and anxiety symptom severity (ASS) is unclear. Methods In order to clarify the relationship between ER skills and ASS symptoms, we assessed skills and symptoms in 131 individuals twice over a 5‐year interval. Cross‐lagged panel analyses were conducted to test whether ER skills were a significant predictor of subsequent ASS or vice versa. Additionally, we explored whether specific ER skills differed in regard to the strength of prospective associations with subsequent ASS. Results ER skills negatively predicted subsequent ASS over and above the effects of baseline ASS (whereas anxiety symptoms did not predict subsequent ER deficits). Acceptance, tolerance, and willingness to confront had the strongest prospective effects on lower subsequent ASS. Conclusions General ER skills may play an important role in the development and maintenance of anxiety disorders.

  October 21, 2013   doi: 10.1002/da.22198   open full text
• Corticotropin Releasing Hormone Receptor 2 (Crhr‐2) Gene Is Associated With Decreased Risk And Severity Of Posttraumatic Stress Disorder In Women.
  Erika J. Wolf, Karen S. Mitchell, Mark W. Logue, Clinton T. Baldwin, Annemarie F. Reardon, Donald E. Humphries, Mark W. Miller.
  Depression and Anxiety. October 09, 2013
  Background The corticotropin releasing hormone (CRH) system has been implicated in a variety of anxiety and mood‐based symptoms and disorders. CRH receptor‐2 (CRHR‐2) plays a role in attenuating biological responses to stressful life events and trauma, making the CRHR‐2 gene a strong candidate to study in relationship to PTSD. Methods The sample was 491 trauma‐exposed white non‐Hispanic veterans and their cohabitating intimate partners assessed via structured interview for lifetime DSM‐IV PTSD; just over 60% met criteria for the disorder. Thirty‐one single nucleotide polymorphisms (SNPs) in and near CRHR‐2, obtained from an array of 2.5 million markers, were tested for association with PTSD diagnosis and symptom severity in the whole sample and in men and women separately. Results Ten SNPs showed nominally significant evidence of association with PTSD in the full sample and two SNPs (rs8192496 and rs2190242) were significant after permutation‐based multiple testing correction (uncorrected ps = .0004 and .0005, odds ratios = .60 and .58, respectively). Analyses stratified by sex revealed that the effect was specific to women, who comprised 35% of the sample (uncorrected ps = .0003 and .0002, odds ratios = .41 and .35, respectively). Two additional SNPs (rs2267715 and rs2284218) also showed significant association with PTSD in women (both uncorrected ps = .001, both odds ratios = .48). Conclusions Results suggest that CRHR‐2 variants may affect risk for PTSD in women by attenuating the stress response and reducing symptoms of the disorder.

  October 09, 2013   doi: 10.1002/da.22176   open full text
• Season Of Birth In Obsessive‐Compulsive Disorder.
  Chin Cheng, Ching‐Heng Lin, Po‐Han Chou, Chia‐Jui Tsai, Tsuo‐Hung Lan, Gerald Nestadt.
  Depression and Anxiety. October 09, 2013
  Background Effects of season of birth (SOB) have been documented in numerous neuropsychiatric disorders. To date, few studies have evaluated this issue in obsessive‐compulsive disorder (OCD). The aim of this study was to investigate the birth seasonality in OCD. Methods This study was based on Taiwan National Health Insurance Research Database. Data for the birth‐year period 1956–1991 were extracted for analysis (273,837 males and 292,207 females). The International Classification of Diseases, 9th Revision, Clinical Modification (ICD‐9‐CM), code 300.3 was used as the diagnosis of OCD. Birth seasonality was compared between the OCD patients (519 males and 528 females) and the general population. Results The birth distributions across the 12 months were significantly different between the OCD patients and the general population (P‐value for the Walter & Elwood's test = .04). A significant decrease of births from March to July and an excess from August to November in OCD patients as compared to the general population was noted (the relative risk of these months vs. the rest months of the year: 0.85 (95% CI 0.74–0.96) and 1.19 (95% CI 1.05–1.36). Effects of SOB in OCD were present in males (P‐value for the Walter & Elwood's test = .03) but not in females. Conclusion The findings support an effect of SOB in people with OCD, especially for men.

  October 09, 2013   doi: 10.1002/da.22200   open full text
• Neighborhood Characteristics And Differential Risk For Depressive And Anxiety Disorders Across Racial/Ethnic Groups In The United States.
  Margarita Alegría, Kristine M. Molina, Chih‐Nan Chen.
  Depression and Anxiety. October 07, 2013
  Background The prevalence of psychiatric disorders varies depending on the person's neighborhood context, their racial/ethnic group, and the specific diagnoses being examined. Less is known about specific neighborhood features that represent differential risk for depressive and anxiety disorders (DAD) across racial/ethnic groups in the United States. This study examines whether neighborhood etiologic factors are associated with DAD, above and beyond individual‐level characteristics, and whether these associations are moderated by race/ethnicity. Methods We utilized nationally representative data (N = 13,837) from the Collaborative Psychiatric Epidemiology Studies (CPES‐Geocode file). Separate weighted multilevel logistic regression models were fitted for any past‐year depressive and/or anxiety disorder, any depressive disorder only, and any anxiety disorder only. Results After adjusting for individual‐level characteristics, African Americans living in a neighborhood with greater affluence and Afro‐Caribbeans residing in more residentially unstable neighborhoods were at increased risk for any past‐year depressive disorder as compared to their non‐Latino white counterparts. Further, Latinos residing in neighborhoods with greater levels of Latino/immigrant concentration were at increased risk of any past‐year anxiety disorder. Lastly, Asians living in neighborhoods with higher levels of economic disadvantage were at decreased risk of any past‐year depressive and/or anxiety disorders compared to non‐Latino whites, independent of individual‐level factors. Differences across subethnic groups are also evident. Conclusions Results suggest neighborhood characteristics operate differently on risk for DAD across racial/ethnic groups. Our findings have important implications for designing and targeting interventions to address DAD risk among racial/ethnic minorities.

  October 07, 2013   doi: 10.1002/da.22197   open full text
• The Remission From Depression Questionnaire As An Outcome Measure In The Treatment Of Depression.
  Mark Zimmerman, Jennifer H. Martinez, Naureen Attiullah, Michael Friedman, Cristina Toba, Daniela A. Boerescu.
  Depression and Anxiety. October 02, 2013
  Background The Remission from Depression Questionnaire (RDQ) assesses multiple domains considered by depressed patients to be relevant to the construct of remission. The present study is the first to examine the validity of the RDQ as an outcome measure. Methods One hundred fifty‐three depressed patients who presented for treatment, or who were in ongoing treatment and had their medication changed, were evaluated at baseline and at 4‐month follow‐up. In addition to the RDQ, the patients completed the Quick Inventory of Depressive Symptomatology (QIDS), and they were rated on 17‐item Hamilton Rating Scale for Depression (HAMD). Results The patients showed significant levels of improvement from baseline to 4 months on each scale. The effect size of the RDQ total score was similar to the effect sizes of the HAMD and QIDS. Both the RDQ and QIDS were significantly associated with patients’ self‐reported remission status. However, the RDQ remained significantly associated with remission status after controlling for QIDS scores, whereas the QIDS was not associated with remission status after controlling for RDQ scores. Discussion The RDQ is as sensitive to change as purely symptom‐based scales such as the QIDS and HAMD. Moreover, the RDQ accounts for variation in patients’ self‐perceived remission status after controlling for QIDS scores, but the reverse was not true. The RDQ allows clinicians and researchers to gain a broader perspective of depressed patients’ status than purely symptom measures, and is more consistent with a biopsychosocial approach toward the treatment of depression.

  October 02, 2013   doi: 10.1002/da.22178   open full text
• Augmentation Of Fluoxetine With Lovastatin For Treating Major Depressive Disorder, A Randomized Double‐Blind Placebo Controlled‐Clinical Trial.
  Ahmad Ghanizadeh, Arvin Hedayati.
  Depression and Anxiety. September 30, 2013
  Backgrounds There are contradictory evidence about the effect of statins on depression. This 6‐week‐randomized placebo‐controlled clinical trial assessed the efficacy and safety of lovastatin as an adjuvant agent for treating major depressive disorder (MDD). Methods The participants were 68 patients with MDD according to DSM‐IV diagnostic criteria. The sample was randomly allocated into fluoxetine (up to 40 mg/day) plus lovastatin (30 mg/day) group or fluoxetine plus placebo group. Hamilton Depression Rating scale was used to measure depression score at baseline, week 2, and week 6. Results Both groups showed a significant decrease of depression score on the Hamilton Depression scale. However, the treatment group decreased depression score more than placebo group [12.8(6.3) vs. 8.2(4.0), t = 3.4, df = 60, P < .001]. Any serious adverse effect was not found. Discussion These results suggest that lovastatin as an adjuvant treatment may be effective for treating patients with MDD.

  September 30, 2013   doi: 10.1002/da.22195   open full text
• Mothers' Own Recollections Of Being Parented And Risk Of Offspring Depression 18 Years Later: A Prospective Cohort Study.
  Liam Mahedy, Jon Heron, Lexine A. Stapinski, Rebecca M. Pearson, Jonathan Evans, Carol Joinson, Lucy Bowes, Glyn Lewis.
  Depression and Anxiety. September 19, 2013
  Background Although the relationship between maternal bonding and risk of offspring depression has been demonstrated, it is unclear whether this risk exists for subsequent generations. This study examines the association between maternal reports of her own mother's parenting and later risk of depression in offspring at age 18. Method This study is based on data from the Avon Longitudinal Study of Parents and Children. Mothers enrolled in the study, completed the Parental Bonding Instrument to provide an assessment of how they were parented by their own mothers up to the age of 16. Offspring depression was assessed at age of 18 using the Clinical Interview Schedule‐Revised. The sample comprised 10,405 respondents who had completed the Parental Bonding Instrument during the antenatal period. Results were adjusted for grandmother's history of depression, maternal depression, and a range of socioeconomic variables. Results A one standard deviation increase in mothers’ perceived lack of care in their own childhood was associated with a 16% increase in the odds of offspring depression at age 18 (odds ratios = 1.16, 95% confidence intervals = [1.04, 1.30]). This effect remained following adjustment for potential confounders (odds ratios = 1.14, 95% confidence intervals = [1.02, 1.27]). There was no evidence for an association between overprotection and offspring depression. Conclusions This study is consistent with the hypothesis that sensitive caregiving is important to future risk of depression across generations. Preventative interventions could be aimed at promoting positive parenting practices, which may help to reduce the risk of depression in subsequent generations.

  September 19, 2013   doi: 10.1002/da.22174   open full text
• Longitudinal Follow‐Up Study Of Adolescents Who Report A Suicide Attempt: Aspects Of Suicidal Behavior That Increase Risk Of A Future Attempt.
  Regina Miranda, Eva Jaegere, Kathleen Restifo, David Shaffer.
  Depression and Anxiety. September 18, 2013
  Background Previous studies have noted that a past suicide attempt (SA) predicts a future SA, but few studies have reported whether previous SAs that predict a future attempt differ from those that do not. Knowing which characteristics of previous SAs predict future attempts would assist in evaluating adolescents at risk of attempt repetition. This longitudinal study of an unreferred sample examined which characteristics of adolescent SAs increased risk for repeat attempts. Methods Fifty‐four adolescents who had attempted suicide were identified through a two‐stage screening of 1,729 high school students. Adolescents reported details of their past SA on the Adolescent Suicide Interview and were reassessed 4–6 years later by telephone. Results Eighteen of the 54 teens (33%) reported that they had made another SA since baseline, and 17 of these reported characteristics of their later attempt. The odds of a further attempt were significantly increased by being alone (OR = 6.1, 95% CI = 1.1–34.8), retrospectively reporting a serious wish to die (OR = 5.2, 95% CI = 1.2–22.7), and planning the attempt for an hour or more (OR = 5.1, 95% CI = 1.1–25.0). The method of attempt remained consistent from baseline to follow‐up attempt (κ = .67). Conclusions Screening high school students to identify those who are at risk for making future SAs should include questions about number of previous SAs and such indicators of risk as isolation, wish to die, and extent of planning prior to a SA.

  September 18, 2013   doi: 10.1002/da.22194   open full text
• Developmental Inter‐Relations Between Early Maternal Depression, Contextual Risks, And Interpersonal Stress, And Their Effect On Later Child Cognitive Functioning.
  Sarah K. G. Jensen, Iroise Dumontheil, Edward D. Barker.
  Depression and Anxiety. September 11, 2013
  Background Maternal depression and contextual risks (e.g. poverty) are known to impact children's cognitive and social functioning. However, few published studies have examined how stress in the social environment (i.e. interpersonal stress) might developmentally inter‐relate with maternal depression and contextual risks to negatively affect a child in these domains. This was the purpose of the current study. Method Mother‐child pairs (n = 6979) from the Avon Longitudinal Study of Parents were the study participants. Mothers reported on depression, contextual risks, and interpersonal stress between pregnancy and 33 months child age. At age 8, the children underwent cognitive assessments and the mothers reported on the children's social cognitive skills. Results Maternal depression, contextual risks, and interpersonal stress showed strong continuity and developmental inter‐relatedness. Maternal depression and contextual risks directly predicted a range of child outcomes, including executive functions and social cognitive skills. Interpersonal stress worked indirectly via maternal depression and contextual risks to negatively affect child outcomes. Conclusion Maternal depression and contextual risks each increased interpersonal stress in the household, which, in turn, contributed to reduced child cognitive and social functioning.

  September 11, 2013   doi: 10.1002/da.22147   open full text
• Energy Drink Consumption Is Associated With Anxiety In Australian Young Adult Males.
  Georgina S.A. Trapp, Karina Allen, Therese A. O'Sullivan, Monique Robinson, Peter Jacoby, Wendy H. Oddy.
  Depression and Anxiety. September 09, 2013
  Background Energy drinks are predominantly targeted to young adult consumers; however, there has been limited research into their effects on psychological functioning in this demographic group. This study examined cross‐sectional associations between energy drink consumption and mental health in a population‐based sample of young adults participating in the Western Australian Pregnancy Cohort (Raine) Study. Methods We used self‐report questionnaires to assess energy drink consumption and mental health (Depression Anxiety Stress Scale‐21; DASS‐21) at the 20‐year cohort follow‐up. In the regression analyses, we considered associations between energy drink consumption (mL/day) and continuous DASS‐21 scores, adjusting for sociodemographic variables, alcohol and drug use, physical activity, body mass index (BMI), and dietary intake. Our sample included 502 males and 567 females (mean age 20 ± 3 years). Results After adjusting for potential confounding factors and controlling for coexisting mental health problems, energy drink consumption (per 100 mL/day) was significantly associated with anxiety (but not depression or stress), and this relationship was found only in males (β = 0.32; 95% CI = 0.05, 0.58). Conclusions Our study found that energy drink consumption was associated with increased anxiety in young adult males. Further research into the possible contribution of energy drink use to the development of mental health problems in young adults is needed.

  September 09, 2013   doi: 10.1002/da.22175   open full text
• Cumulative Traumas And Risk Thresholds: 12‐Month Ptsd In The World Mental Health (Wmh) Surveys.
  Elie G. Karam, Matthew J. Friedman, Eric D. Hill, Ronald C. Kessler, Katie A. McLaughlin, Maria Petukhova, Laura Sampson, Victoria Shahly, Matthias C. Angermeyer, Evelyn J. Bromet, Giovanni Girolamo, Ron Graaf, Koen Demyttenaere, Finola Ferry, Silvia E. Florescu, Josep Maria Haro, Yanling He, Aimee N. Karam, Norito Kawakami, Viviane Kovess‐Masfety, María Elena Medina‐Mora, Mark A. Oakley Browne, José A. Posada‐Villa, Arieh Y. Shalev, Dan J. Stein, Maria Carmen Viana, Zahari Zarkov, Karestan C. Koenen.
  Depression and Anxiety. August 27, 2013
  Background Clinical research suggests that posttraumatic stress disorder (PTSD) patients exposed to multiple traumatic events (TEs) rather than a single TE have increased morbidity and dysfunction. Although epidemiological surveys in the United States and Europe also document high rates of multiple TE exposure, no population‐based cross‐national data have examined this issue. Methods Data were analyzed from 20 population surveys in the World Health Organization World Mental Health Survey Initiative (n = 51,295 aged 18+). The Composite International Diagnostic Interview (3.0) assessed 12‐month PTSD and other common DSM‐IV disorders. Respondents with 12‐month PTSD were assessed for single versus multiple TEs implicated in their symptoms. Associations were examined with age of onset (AOO), functional impairment, comorbidity, and PTSD symptom counts. Results 19.8% of respondents with 12‐month PTSD reported that their symptoms were associated with multiple TEs. Cases who associated their PTSD with four or more TEs had greater functional impairment, an earlier AOO, longer duration, higher comorbidity with mood and anxiety disorders, elevated hyperarousal symptoms, higher proportional exposures to partner physical abuse and other types of physical assault, and lower proportional exposure to unexpected death of a loved one than cases with fewer associated TEs. Conclusions A risk threshold was observed in this large‐scale cross‐national database wherein cases who associated their PTSD with four or more TEs presented a more “complex” clinical picture with substantially greater functional impairment and greater morbidity than other cases of PTSD. PTSD cases associated with four or more TEs may merit specific and targeted intervention strategies.

  August 27, 2013   doi: 10.1002/da.22169   open full text
• Recurrence Of Major Depressive Episodes Is Strongly Dependent On The Number Of Previous Episodes.
  Andrew Bulloch, Jeanne Williams, Dina Lavorato, Scott Patten.
  Depression and Anxiety. August 26, 2013
  Background A history of past major depressive episodes (MDEs) is known to be a risk factor for future MDEs. Additional information about the relationship between past and future episodes would be useful in clinical practice, it is therefore important to fully understand the epidemiology of major depression. We asked whether the number of previous MDEs is related to the probability of recurrence in the general population. Methods Data were used from the Canadian National Population Health Survey (NPHS) that was repeated every 2 years from 1994/1995 to 2009/2010 (i.e., nine cycles). Prior year depression was assessed with the Composite International Diagnostic Interview Short Form (CIDI‐SF). We estimated the total number of MDEs in individuals over the first eight cycles and examined recurrence in the ninth cycle. These analyses employed a generalized linear model (identity link) where recurrence in cycle 9 was the outcome and the predictor variables were age, gender, and the number of MDEs in the first eight cycles. Results The risk for recurrence of depression in cycle 9 was found to progressively increase with the number of prior episodes, reaching a value of greater than 46% when the number of prior episodes was five to eight. Independent of this association, the risk of recurrence was greater in younger people and women, but the strength of association of these variables was much weaker for past episodes. Conclusions MDE recurrence strongly depended on the number of preceding episodes. Those at highest risk of recurrence can be easily identified by their number of past episodes.

  August 26, 2013   doi: 10.1002/da.22173   open full text
• Does Relational Dysfunction Mediate The Association Between Anxiety Disorders And Later Depression? Testing An Interpersonal Model Of Comorbidity.
  Lisa R. Starr, Constance Hammen, Nicole Phillips Connolly, Patricia A. Brennan.
  Depression and Anxiety. August 26, 2013
  Background Anxiety disorders tend to precede onset of comorbid depression. Several researchers have suggested a causal role for anxiety in promoting depressive episodes, but few studies have identified specific mechanisms. The current study proposes an interpersonal model of comorbidity, where anxiety disorders disrupt interpersonal functioning, which in turn elevates risk for depression. Methods At age 15 (T1), 815 adolescents oversampled for maternal depression completed diagnostic interviews, social chronic stress interviews, and self‐report measures. At age 20 (T2), participants repeated all measures and reported on self‐perceived interpersonal problems. At approximately age 23 (T3), a subset of participants (n = 475) completed a self‐report depressive symptoms measure. Results Consistent with other samples, anxiety disorders largely preceded depressive disorders. Low sociability and interpersonal oversensitivity mediated the association between T1 social anxiety disorder and later depression (including T2 depressive diagnosis and T3 depressive symptoms), controlling for baseline. Interpersonal oversensitivity and social chronic stress similarly mediated the association between generalized anxiety disorder before age 15 and later depression. Conclusions Interpersonal dysfunction may be one mechanism through which anxiety disorders promote later depression, contributing to high comorbidity rates.

  August 26, 2013   doi: 10.1002/da.22172   open full text
• Sleep Quality Predicts Treatment Outcome In Cbt For Social Anxiety Disorder.
  Alyson K. Zalta, Sheila Dowd, David Rosenfield, Jasper A. J. Smits, Michael W. Otto, Naomi M. Simon, Alicia E. Meuret, Luana Marques, Stefan G. Hofmann, Mark H. Pollack.
  Depression and Anxiety. August 26, 2013
  Background Sleep quality may be an important, yet relatively neglected, predictor of treatment outcome in cognitive‐behavioral therapy (CBT) for anxiety disorders. Specifically, poor sleep quality may impair memory consolidation of in‐session extinction learning. We therefore examined sleep quality as a predictor of treatment outcome in CBT for social anxiety disorder and the impact of d‐cycloserine (DCS) on this relationship. Methods One hundred sixty‐nine participants with a primary diagnosis of DSM‐IV generalized social anxiety disorder were recruited across three sites. Participants were enrolled in 12 weeks of group CBT. Participants randomly received 50 mg of DCS (n = 87) or pill placebo (n = 82) 1 hr prior to sessions 3–7. Participants completed a baseline measure of self‐reported sleep quality and daily diaries recording subjective feelings of being rested upon wakening. Outcome measures including social anxiety symptoms and global severity scores were assessed at each session. Results Poorer baseline sleep quality was associated with slower improvement and higher posttreatment social anxiety symptom and severity scores. Moreover, patients who felt more “rested” after sleeping the night following a treatment session had lower levels of symptoms and global severity at the next session, controlling for their symptoms and severity scores the previous session. Neither of these effects were moderated by DCS condition. Conclusions Our findings suggest that poor sleep quality diminishes the effects of CBT for social anxiety disorder and this relation is not attenuated by DCS administration. Therapeutic attention to sleep quality prior to initiation of CBT and during the acute treatment phase may be clinically indicated.

  August 26, 2013   doi: 10.1002/da.22170   open full text
• Acute And Chronic Stress Exposure Predicts 1‐Year Recurrence In Adult Outpatients With Residual Depression Symptoms Following Response To Treatment.
  Kate L. Harkness, Jordan E. Theriault, Jeremy G. Stewart, R. Michael Bagby.
  Depression and Anxiety. August 23, 2013
  Background One of the strongest predictors of depression recurrence in those who respond to treatment is the presence of residual depressive symptoms. Our goal was to examine stressful life event exposure as a mechanism of recurrence in previously depressed patients with residual depression symptoms. That is, we predicted that higher levels of residual symptoms will significantly predict exposure to acute life events that will then heighten prospective recurrence risk. Methods Participants included 68 adult outpatients with major depression (42 women; age 18–60) who completed a 12‐month naturalistic follow‐up after achieving remission in a 20‐week randomized, open label trial of interpersonal psychotherapy, cognitive‐behavioral therapy, or antidepressant medication. Depression recurrence was defined as the reemergence of an episode of major depression as determined by structured interview. Acute life events and chronic stressors were assessed at the end of follow‐up using a contextual interview. Results Posttreatment depression scores significantly prospectively predicted an increased risk for recurrence, and acute life events in the follow‐up period. Cox regression survival analyses modeling life events as time‐dependent covariates showed that life event exposure mediated the relation of residual symptoms to recurrence even controlling for chronic stress. Conclusions Our findings implicate residual symptoms in heightening depression recurrence risk through exposure to stressful life events. Depression recurrence adds significantly to the burden of the disorder. Therefore, rigorous follow‐up of patients targeting the stressful context has the potential to prevent a lifelong pattern of illness.

  August 23, 2013   doi: 10.1002/da.22177   open full text
• Enhancing Hispanic Participation In Mental Health Clinical Research: Development Of A Spanish‐Speaking Depression Research Site.
  Vivianne Aponte‐Rivera, Boadie W. Dunlop, Cynthia Ramirez, Mary E. Kelley, Rebecca Schneider, Beatriz Blastos, Jacqueline Larson, Flavia Mercado, Helen Mayberg, W. Edward Craighead.
  Depression and Anxiety. August 19, 2013
  Background Hispanics, particularly those with limited English proficiency, are underrepresented in psychiatric clinical research studies. We developed a bilingual and bicultural research clinic dedicated to the recruitment and treatment of Spanish‐speaking subjects in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study, a large clinical trial of treatment‐naïve subjects with major depressive disorder (MDD). Methods Demographic and clinical data derived from screening evaluations of the first 1,174 subjects presenting for participation were compared between the Spanish‐speaking site (N = 275) and the primary English‐speaking site (N = 899). Reasons for ineligibility (N = 888) for the PReDICT study were tallied for each site. Results Compared to English speakers, Spanish speakers had a lower level of education and were more likely to be female, uninsured, and have uncontrolled medical conditions. Clinically, Spanish speakers demonstrated greater depression severity, with higher mean symptom severity scores, and a greater number of previous suicide attempts. Among the subjects who were not randomized into the PReDICT study, Spanish‐speaking subjects were more likely to have an uncontrolled medical condition or refuse participation, whereas English‐speaking subjects were more likely to have bipolar disorder or a non‐MDD depressive disorder. Conclusion Recruitment of Hispanic subjects with MDD is feasible and may enhance efforts at signal detection, given the higher severity of depression among Spanish‐speaking participants presenting for clinical trials. Specific approaches for the recruitment and retention of Spanish‐speaking participants are required.

  August 19, 2013   doi: 10.1002/da.22153   open full text
• Postdeployment Threat‐Related Attention Bias Interacts With Combat Exposure To Account For Ptsd And Anxiety Symptoms In Soldiers.
  Maurice L. Sipos, Yair Bar‐Haim, Rany Abend, Amy B. Adler, Paul D. Bliese.
  Depression and Anxiety. August 19, 2013
  Background Recent studies suggest that assessment of threat‐related attention bias may be useful in identifying soldiers at risk for clinical symptoms. The present study assessed the degree to which soldiers experienced combat events and showed attentional threat avoidance affected their reported levels of post‐traumatic stress disorder (PTSD) and anxiety symptoms. Methods Four months after a combat deployment to Iraq, 63 US soldiers completed a survey assessing combat exposures and clinical symptoms as well as a dot‐probe task assessing threat‐related attention bias. Results Significant three‐way interactions regressing threat reaction times (RTs), neutral RTs, and combat exposure on PTSD and anxiety symptoms were observed. Specifically, soldiers with high levels of combat exposure, who were more likely to demonstrate attentional bias away from threat, were also more symptomatic. Conclusion These results demonstrate the potential of threat‐related attention bias as a behavioral marker of PTSD and anxiety symptoms in a high‐risk military occupational context.

  August 19, 2013   doi: 10.1002/da.22157   open full text
• Is Dental Phobia A Blood‐Injection‐Injury Phobia?
  C.M.H.H. Houtem, I.H.A. Aartman, D.I. Boomsma, L. Ligthart, C.M. Visscher, A. Jongh.
  Depression and Anxiety. August 19, 2013
  Background Dental phobia is part of the Blood‐Injection‐Injury (B‐I‐I) phobia subtype of specific phobia within DSM‐IV‐TR. To investigate the conceptual validity of this classification, the purpose of the present study was to determine the co‐occurrence of dental phobia, typical dental (and B‐I‐I related) fears, vasovagal fainting, and avoidance of dental care. Method Data were collected by an online survey in Dutch twin families (n = 11,213). Results Individuals with a positive screen of dental phobia (0.4% of the sample) rated typical B‐I‐I‐related stimuli as relatively little anxiety provoking (e.g. of all 28 fears the stimulus “the sight of blood” was ranked lowest). Presence of dental phobia was significantly associated with a history of dizziness or fainting during dental treatment (OR = 3.4; 95% CI: 1.5–8.1), but of the dental phobic individuals only 13.0% reported a history of dizziness or fainting during dental treatment. Presence of dental phobia (OR = 5.0; 95% CI: 2.8–8.8) was found to be associated with avoidance of dental care, but a history of dizziness or fainting during dental treatment was not (OR = 1.0; 95% CI: 0.8–1.2). Conclusions The present findings converge to the conclusion that dental phobia should be considered a specific phobia subtype independent of the B‐I‐I cluster within the DSM classification system.

  August 19, 2013   doi: 10.1002/da.22168   open full text
• Depression And Exposure To Suicide Predict Suicide Attempt.
  Sonali Nanayakkara, Diane Misch, Laura Chang, David Henry.
  Depression and Anxiety. August 15, 2013
  Objective To examine the role of depression and exposure to peer or family suicide and their interaction as risk factors for adolescent suicide attempts. Methods The study used the public‐use data set of the National Longitudinal Study of Adolescent Health (Add Health), which is a nationally representative stratified sample of U.S. high school students. Sample size was 4,719. Analyses predicted suicide attempts from preexisting depression and exposure to suicide of a friend or family member, controlling for previous suicide attempts, exposure, and depression. Results The greatest risk for future suicide attempts (relative risk = 3.3), was attributable to an attempt in the preceding year, controlling for preexisting and current depression and exposure. There was a main effect of exposure with the next highest relative risk of 3.2. A similar risk ratio, 3.2, was found for the difference between no depression and current severe depression, controlling for past depression and attempts. There was no evidence of an interaction between exposure to a peer or family member suicide attempt and depression. Supplementary analyses found that exposure to a friend or family member suicide attempt or completed suicide each added significantly to risk for adolescents regardless of depression levels. Conclusion Exposure to suicidal behavior in a friend or family member poses risk equivalent to the risk posed by becoming severely depressed. Attending to such risks could benefit clinical practice with adolescence and public health suicide prevention efforts.

  August 15, 2013   doi: 10.1002/da.22143   open full text
• Family Aggregation And Risk Factors Of Obsessive–Compulsive Disorders In A Nationwide Three‐Generation Study.
  Hans‐Christoph Steinhausen, Charlotte Bisgaard, Povl Munk‐Jørgensen, Dorte Helenius.
  Depression and Anxiety. August 06, 2013
  Background This nationwide register‐based study investigates how often obsessive–compulsive disorders (OCD) with different age at diagnosis occur in affected families compared to control families. Furthermore, the study addresses the impact of certain risk factors, that is, sex, degree of urbanization, year of birth, and maternal and paternal age at birth. Methods A total of N = 2,057 child and adolescent psychiatric subjects born between 1952 and 2000 and registered in the Danish Psychiatric Central Research Register developed OCD before the age of 18. In addition, N = 6,055 controls without any psychiatric diagnosis before age 18 and matched for age, sex, and residential region were included. Psychiatric diagnoses were also obtained for the first‐degree relatives as a part of the Danish Three‐Generation Study. A family load component was obtained by using various mixed regression models. Results OCD occurred significantly more often in case than in control families. Having a mother, father, sibling, or an offspring with the disorder was proven to be a risk factor. Maternal age above 35 years, male sex by tendency, and ascending year of birth were associated with having OCD. Furthermore, case relatives did not develop OCD earlier than control relatives. The risk of OCD in the case probands was significantly increased when first‐degree family members had either OCD, or tic disorders, or affective disorders, or anxiety disorders. Conclusions These findings based on a very large and representative dataset provide further and very solid evidence for the high family aggregation of OCD.

  August 06, 2013   doi: 10.1002/da.22163   open full text
• Synchronous Telehealth Technologies In Psychotherapy For Depression: A Meta‐Analysis.
  Janyce E. Osenbach, Karen M. O'Brien, Matthew Mishkind, Derek J. Smolenski.
  Depression and Anxiety. August 06, 2013
  Background Many patients suffering from depression lack immediate access to care. The use of synchronous telehealth modalities to deliver psychotherapy is one solution to this problem. This meta‐analysis examined differences in treatment efficacy for psychotherapy administered via synchronous telehealth as compared to standard nontelehealth approaches. Method We located 14 articles that met inclusion criteria of the use of a synchronous telehealth modality for treatment compared to a standard nontelehealth modality comparison group. Results Overall, a statistically significant systematic difference between modes of delivery was not identified (g = 0.14, SE = 0.08, 95% CI = [−0.03, 0.30], P = .098, I2 = 49.74%). Stratification methods and metaregression were used to analyze the contributions of type of comparison group, intervention modality, and targeted mental health outcome to moderation of effect size (ES) estimates and heterogeneity. Type of comparison group (face‐to‐face versus care‐as‐usual) had the strongest influence on observed heterogeneity and moderated the summary ES. The only detectable difference in efficacy was restricted to studies that used care‐as‐usual as the comparison group (g = 0.29, SE = 0.06, 95% CI = [0.16, 0.41], P < .001, I2 = 5.14%). Conclusions Overall, we found no evidence to suggest that the delivery of psychotherapy via synchronous telehealth modalities is less effective than nontelehealth means in reducing depression symptoms.

  August 06, 2013   doi: 10.1002/da.22165   open full text
• Psychological Distress And Comorbid Physical Conditions: Disease Or Disability?
  Julie E. Byles, Ian Robinson, Emily Banks, Richard Gibson, Lucy Leigh, Bryan Rodgers, Cassie Curryer, Louisa Jorm.
  Depression and Anxiety. August 06, 2013
  Background The relationship between comorbidity and psychological distress is well documented, however the mechanism of this association is unclear. We aim to assess the extent to which the association between common chronic conditions and high scores on the Kessler Psychological Distress Scale (K10) measure of psychological distress vary according to comorbid conditions, disability, and sociodemographic circumstances. Methods Analysis of self‐reported cross‐sectional data from the New South Wales 45 and Up Study, Australia, for 236,508 participants aged 45 years and over, using logistic regression modeling. Results Self‐reported heart attack/angina, other heart disease, stroke, and diabetes were all significantly associated with higher risk of high/very high K10 scores. These associations were attenuated, but remained statistically significant, when comorbidity, disability, and sociodemographic factors were added to the model. Men reporting needing help for daily tasks were nine times as likely to report high/very high K10 scores as those without this need, and women reporting needing help were seven times more likely to have high/very high K10 scores. Conclusions Heart attack/angina, other heart disease, stroke, and diabetes are all significantly associated with psychological distress. However, these effects are partly explained by other comorbid conditions, limitations on physical functioning, and sociodemographic factors. These findings highlight the importance of developing public health policies that encompass psychological, physiological, and social domains, and provide crucial insights for clinicians in identifying and supporting those people at risk of psychological distress.

  August 06, 2013   doi: 10.1002/da.22162   open full text
• Comparison Of Criminal Activity Between Israeli Veterans With And Without Ptsd.
  Shany Sherman, Leah Fostick, Joseph Zohar,.
  Depression and Anxiety. August 02, 2013
  Background The literature, based on US Vietnam veterans, suggests that posttraumatic stress disorder (PTSD) is associated with increased criminal activity, especially violence, alcohol, and drug abuse, although more recent studies, which tested data from the United States as well as the United Kingdom, suggest a more moderate effect for this relationship. The current study examines Israeli veterans, who differ socioeconomically and have lower rates of substance abuse than veterans in previous studies. Methods In this study, the social security numbers of 2,235 male veterans with PTSD and 2,235 matched control male veterans without a PTSD diagnosis were checked for criminal records in the Israeli Police criminal records database. Severity measures were also obtained for 273 veterans who are currently treated for PTSD by the Ministry of Defense. Results PTSD diagnosed veterans, as compared to controls, were slightly more likely to have criminal records (43%, n = 957/2235 versus 36%, n = 803/2235, Chi‐ square = 22.23, P < 0.001, OR = 1.33). This was due to a small difference in “Violence” and “Crimes against public order and legal authority.” No difference was found in drugs or any other categories. In addition, criminal activity was not related to symptoms severity. More veterans with PTSD had their first criminal record after the traumatic event. Conclusions Contrary to previous findings, in this large national cohort, only slight association was found between PTSD and criminal activity. The unique sample of Israeli veterans might account for this difference and suggest that PTSD per se might not be linked to increased criminal activity, violence, or substance abuse.

  August 02, 2013   doi: 10.1002/da.22161   open full text
• Cortisol Awakening Response In Adolescents With Acute Sexual Abuse Related Posttraumatic Stress Disorder.
  Brooks R. Keeshin, Jeffrey R. Strawn, Dorothee Out, Douglas A. Granger, Frank W. Putnam.
  Depression and Anxiety. July 24, 2013
  Background Little is known regarding changes in the hypothalamic‐pituitary‐adrenal axis (HPA axis) of adolescent girls with and without posttraumatic stress disorder (PTSD) who have recently experienced sexual abuse. Therefore, in this pilot study, we utilized non‐stressed home saliva collection three times a day for three days to assess the levels, diurnal variation and awakening response of cortisol in recently sexually abused adolescent girls. Methods Twenty‐four adolescent girls (mean age: 15 ± 1.5 years) with a history of recent sexual abuse (sexual abuse occurred 1–6 months prior to study enrollment) and 12 healthy, nontraumatized comparison subjects (mean age: 14.8 ± 1.3 years) collected saliva at home upon awakening, 30 min after waking, and in the late afternoon on three consecutive school days. Results Among sexually abused girls, flattening of the morning cortisol awakening response was associated with PTSD severity (r = −.41, P < .05) as well as intrusive symptoms (r = −.42, P < .05). Increased adversity prior to sexual abuse was also associated with flattening of the cortisol awakening response (r = −.53, P < .01). Conclusions Attenuation of the cortisol awakening response in recently sexually abused girls suggests that alterations in HPA‐axis functioning may occur relatively proximate to the traumatic event and correlate with symptom severity of PTSD, intrusive symptoms, and hyperarousal symptoms. These data raise the possibility that subacute alterations in the dynamic secretion of cortisol are directly related to the pathophysiology of sexual abuse‐related PTSD symptoms in adolescent girls.

  July 24, 2013   doi: 10.1002/da.22154   open full text
• Posttraumatic Stress Disorder Increases Risk For Suicide Attempt In Adults With Recurrent Major Depression.
  Daniel Stevens, Holly C. Wilcox, Dean F. MacKinnon, Francis M. Mondimore, Barbara Schweizer, Dunya Jancic, William H. Coryell, Myrna M. Weissman, Douglas F. Levinson, James B. Potash.
  Depression and Anxiety. July 24, 2013
  Background Genetics of Recurrent Early‐Onset Depression study (GenRED II) data were used to examine the relationship between posttraumatic stress disorder (PTSD) and attempted suicide in a population of 1,433 individuals with recurrent early‐onset major depressive disorder (MDD). We tested the hypothesis that PTSD resulting from assaultive trauma increases risk for attempted suicide among individuals with recurrent MDD. Methods Data on lifetime trauma exposures and clinical symptoms were collected using the Diagnostic Interview for Genetic Studies version 3.0 and best estimate diagnoses of MDD, PTSD, and other DSM‐IV Axis I disorders were reported with best estimated age of onset. Results The lifetime prevalence of suicide attempt in this sample was 28%. Lifetime PTSD was diagnosed in 205 (14.3%) participants. We used discrete time‐survival analyses to take into account timing in the PTSD‐suicide attempt relationship while adjusting for demographic variables (gender, race, age, and education level) and comorbid diagnoses prior to trauma exposure. PTSD was an independent predictor of subsequent suicide attempt (HR = 2.5, 95% CI: 1.6, 3.8; P < .0001). Neither assaultive nor nonassaultive trauma without PTSD significantly predicted subsequent suicide attempt after Bonferroni correction. The association between PTSD and subsequent suicide attempt was driven by traumatic events involving assaultive violence (HR = 1.7, 95% CI: 1.3, 2.2; P< .0001). Conclusions Among those with recurrent MDD, PTSD appears to be a vulnerability marker of maladaptive responses to traumatic events and an independent risk factor for attempted suicide. Additional studies examining differences between those with and without PTSD on biological measures might shed light on this potential vulnerability.

  July 24, 2013   doi: 10.1002/da.22160   open full text
• Role Of Allelic Variants Of Fk506‐Binding Protein 51 (Fkbp5) Gene In The Development Of Anxiety Disorders.
  Alessandra Minelli, Elisabetta Maffioletti, Claude Robert Cloninger, Chiara Magri, Riccardo Sartori, Marco Bortolomasi, Chiara Congiu, Stefano Bignotti, Matilde Segala, Mario Giacopuzzi, Massimo Gennarelli.
  Depression and Anxiety. July 16, 2013
  Background Anxiety disorders exhibit remarkably high rates of comorbidity with major depressive disorder (MDD). Mood and anxiety disorders are considered stress‐related diseases. Genetic variations in the co‐chaperone FK506‐binding protein 51, FKBP5, which modulates the function of glucocorticoid receptors, have been associated with an increased risk for the development of posttraumatic stress disorder, but data regarding its role in MDD are controversial. The aims of this study were to clarify the role of the FKBP5 gene in depression and anxiety disorders through a case–control study and an association study with personality traits using the Temperament and Character Inventory (TCI) in healthy subjects. Methods Six hundred fifty‐seven MDD patients, with or without an anxiety disorder in comorbidity, and 462 healthy volunteers were enrolled in the study. Two hundred fifty‐six controls agreed to fill out the TCI. Results The results showed that the T allele of rs1360780 was more frequent among the patients affected by MDD with a comorbidity of anxiety disorders, compared to those without (P < .001). Among the controls, we found that the T allele more often exhibited personality traits associated with an increased vulnerability to anxiety. Conclusions These results support the hypothesis that allelic variants of FKBP5 are a risk factor for anxiety disorders. The identification of genetic variants involved in anxiety may have implications for the optimization of therapeutic interventions.

  July 16, 2013   doi: 10.1002/da.22158   open full text
• Enduring Influence Of Early Temperament On Neural Mechanisms Mediating Attention–Emotion Conflict In Adults.
  Johanna M. Jarcho, Nathan A. Fox, Daniel S. Pine, Ellen Leibenluft, Tomer Shechner, Kathryn A. Degnan, Koraly Perez‐Edgar, Monique Ernst.
  Depression and Anxiety. July 16, 2013
  Background Behavioral inhibition, a temperament identified in early childhood, is often associated with dysregulated attention and affective processing, particularly in response to threat. Longitudinal studies find that the manifestation of perturbed attention and affective processing often dissipates with age. Yet, childhood behavioral inhibition continues to predict perturbed brain function into adulthood. This suggests that adults with childhood behavioral inhibition may engage compensatory processes to effectively regulate emotion‐related attention. However, it is unknown whether perturbations in brain function reflect compensation for attention bias to emotional stimuli generally, or to threatening contexts more specifically. The present study tests these possibilities. Methods Adults with and without a history of stable childhood behavioral inhibition completed an attention‐control task in the context of threatening and nonthreatening stimuli while undergoing functional magnetic resonance imaging. Participants were asked to identify the gender of fearful (threatening) and happy (nonthreatening) faces, while ignoring both the face emotion and overlaid congruent (low attention control, LAC) or incongruent (high attention control, HAC) gender words. Results When fearful faces were present, adults with stable childhood behavioral inhibition exhibited more activity in striatum, cingulate, and dorsolateral prefrontal cortex for HAC trials compared with LAC trials, relative to those without behavioral inhibition. When happy faces were present, the opposite activation pattern emerged. No group differences in behavior were observed. Conclusions Among adults, stable childhood behavioral inhibition predicts neural, but not behavioral, responding when attention control is engaged in discrete emotional contexts. This suggests a mechanism by which adults may compensate for the behavioral manifestation of threat‐based attention biases.

  July 16, 2013   doi: 10.1002/da.22140   open full text
• Patient‐Reported Outcomes Of Quality Of Life, Functioning, And Depressive Symptom Severity In Major Depressive Disorder Comorbid With Panic Disorder Before And After Ssri Treatment In The Star*D Trial.
  Waguih William IsHak, James Mirocha, Scott Christensen, Fan Wu, Richard Kwock, Joseph Behjat, Sarah Pi, Araks Akopyan, Eric D. Peselow, Robert M. Cohen, David Elashoff.
  Depression and Anxiety. July 16, 2013
  Background Panic disorder (PD) is highly comorbid with major depressive disorder (MDD) with potential impact on patient‐reported outcomes of quality of life (QOL), functioning, and depressive symptom severity. Methods Using data from the sequenced treatment alternatives to relieve depression (STAR*D) trial, we compared entry and post‐SSRI‐treatment QOL, functioning, and depressive symptom severity scores in MDD patients with comorbid PD (MDD+PD) to MDD patients without PD (MDDnoPD). We also compared pre‐ and posttreatment proportions of patients with severe impairments in quality of life and functioning. Results MDD+PD patients experienced significantly lower QOL and functioning and more severe depressive symptoms than MDDnoPD patients at entry. Following treatment with citalopram, both groups showed significant improvements, however, nearly 30–60% of patients still suffered from severe quality of life and functioning impairments. MDD+PD patients exited with lower QOL and functioning than MDDnoPD patients, a difference that became statistically insignificant after adjusting for baseline measures of depressive symptom severity, functioning, and QOL, comorbid anxiety disorders (PTSD, GAD, social, and specific phobias), age, and college education. Conclusions Functional outcomes using QOL and functioning measures should be utilized in treating and researching MDD so that shortfalls in traditional treatment can be identified and additional interventions can be designed to address severe baseline QOL and functioning deficits in MDD comorbid with PD.

  July 16, 2013   doi: 10.1002/da.22152   open full text
• Insula And Anterior Cingulate Gaba Levels In Posttraumatic Stress Disorder: Preliminary Findings Using Magnetic Resonance Spectroscopy.
  Isabelle M. Rosso, Melissa R. Weiner, David J. Crowley, Marisa M. Silveri, Scott L. Rauch, J. Eric Jensen.
  Depression and Anxiety. July 16, 2013
  Background Increased reactivity of the insular cortex and decreased activity of the dorsal anterior cingulate cortex (ACC) are seen in functional imaging studies of posttraumatic stress disorder (PTSD), and may partly explain the persistent fear and anxiety proneness that characterize the disorder. A possible neurochemical correlate is altered function of the inhibitory neurotransmitter gamma‐aminobutyric acid (GABA). We report results from what we believe is the first study applying proton magnetic resonance spectroscopy (1H‐MRS) to measure brain GABA in PTSD. Methods Thirteen adults with DSM‐IV PTSD and 13 matched healthy control subjects underwent single voxel 1H‐MRS at 4 Tesla. GABA was measured in the right anterior insula and dorsal ACC, using Mescher‐Garwood Point‐Resolved Echo Spectroscopy Sequence (MEGAPRESS) spectral editing. Subjects were interviewed with the Structured Clinical Interview for DSM‐IV and the Clinician Administered PTSD Scale, and also completed the State and Trait Anxiety Inventory. Results Insula GABA was significantly lower in PTSD subjects than in controls, and dorsal ACC GABA did not differ significantly between the groups. Insula GABA was not significantly associated with severity of PTSD symptoms. However, lower insula GABA was associated with significantly higher state and trait anxiety in the subject sample as a whole. Conclusions PTSD is associated with reduced GABA in the right anterior insula. This preliminary evidence of the 1H‐MRS GABA metabolite as a possible biomarker of PTSD encourages replication in larger samples and examination of relations with symptom dimensions. Future studies also should examine whether insula GABA is a marker of anxiety proneness, cutting across clinical diagnostic categories.

  July 16, 2013   doi: 10.1002/da.22155   open full text
• Cortico‐Limbic Responses To Masked Affective Faces Across Ptsd, Panic Disorder, And Specific Phobia.
  William D. S. Killgore, Jennifer C. Britton, Zachary J. Schwab, Lauren M. Price, Melissa R. Weiner, Andrea L. Gold, Isabelle M. Rosso, Naomi M. Simon, Mark H. Pollack, Scott L. Rauch.
  Depression and Anxiety. July 16, 2013
  Background Exaggerated amygdala and reduced ventromedial prefrontal cortex (vmPFC) responsiveness during emotional processing have been reported in studies examining individual anxiety disorders. Studies are needed, however, which directly compare activation of amygdalo‐cortical circuitry across multiple anxiety disorders within the same study. Here we compared cortico‐limbic neurocircuitry across three different anxiety disorders using a well‐validated emotional probe task. Methods Sixty‐five adult volunteers, including 22 healthy controls (HC) and participants meeting DSM‐IV criteria for either posttraumatic stress disorder (14 PTSD), panic disorder (14 PD), or specific animal phobia (15 SP), underwent functional magnetic resonance imaging (fMRI) at 3 T while passively viewing backward‐masked images of faces expressing fear, happy, and neutral emotions. Results A group comprising all three anxiety disorders showed greater activation within the left amygdala and reduced activation within the vmPFC compared to the HC group during the masked fear versus neutral condition. Pairwise group comparisons showed that amygdala activation only reached significance for the PTSD versus HCs, whereas decreased vmPFC was only evident for SP and PD groups versus the HC group. Furthermore, activation did not differ among the anxiety groups when contrasted directly with one another. A similar pattern was observed for masked happy versus neutral faces. Conclusions Exclusive of specific diagnostic category, anxiety disorders were generally associated with increased activation of the amygdala and reduced activation within vmPFC. Categorical distinctions were generally weak or not observed and suggest that functional differences may reflect the magnitude of responses within a common neurocircuitry across disorders rather than activation of distinct systems.

  July 16, 2013   doi: 10.1002/da.22156   open full text
• Irritability In Child And Adolescent Anxiety Disorders.
  Joel Stoddard, Argyris Stringaris, Melissa A. Brotman, Daniel Montville, Daniel S. Pine, Ellen Leibenluft.
  Depression and Anxiety. July 01, 2013
  Background Our objective was to compare self‐ and parent‐reported irritability in youths with anxiety disorders, healthy youths, and those with mood disorders characterized by irritability. Irritability is a common but relatively understudied psychiatric symptom in child and adolescent anxiety disorders. In anxious youths, little is known about the severity of irritability, its impact on functioning, or the effect of informant source on reports of irritability. Methods We compared parent‐ and self‐report forms of the Affective Reactivity Index (ARI), a validated measure of irritability, in youths ages 8–17 years with no psychopathology (healthy comparison, HC; n = 38), anxiety disorders (ANX; n = 42), bipolar disorder (BD; n = 35), or severe mood dysregulation (SMD; n = 61; a phenotype characterized by chronic, severely impairing irritability). Results Irritability was significantly higher in ANX than HC youths by both parent and self‐report (partial η2 = 0.24 and 0.22, respectively, P's < 0.001). Informant effects differed among ANX, BD, and SMD. Overall, parent‐reported irritability was higher in BD with comorbid anxiety disorders and SMD with or without comorbid anxiety disorders than ANX (P's < 0.007), but self‐reported irritability was not significantly different among the three patient groups. Discussion By both parent and self‐report, youths with anxiety disorders exhibit significantly more irritability and associated impairment than healthy subjects. Self‐reported irritability in youths with anxiety disorders is comparable to that observed in youths with severe mood disorders, although parental reports of irritability differ among the disorders. Future research should examine the pathophysiology of anxiety‐associated irritability, as well as its prognostic and treatment implications.

  July 01, 2013   doi: 10.1002/da.22151   open full text
• Demographic And Clinical Characteristics Of Consistent And Inconsistent Longitudinal Reporters Of Lifetime Suicide Attempts In Adolescence Through Young Adulthood.
  Shelley R. Hart, Rashelle J. Musci, Nicholas Ialongo, Elizabeth D. Ballard, Holly C. Wilcox.
  Depression and Anxiety. June 26, 2013
  Background Within the context of the recent release of the 2012 National Suicide Prevention Strategy, and as the third leading cause of death for individuals 10‐ to 24‐years‐old, suicide prevention is a national priority. A consistently reported and robust risk factor for suicide is a prior suicide attempt; however few studies have investigated the consistency of self‐reported lifetime suicide attempts. The goal of this study is to describe the prevalence and characteristics of inconsistent reporting of suicide attempt in a longitudinal cohort of participants annually assessed in 12 waves of data collected from middle school (age 12) to early adulthood (age 22). Methods Among this cohort (n = 678), we compared those who consistently, inconsistently, and never reported a suicide attempt according to demographic and clinical variables. Results Almost 90% (88.5%) of our sample inconsistently reported a lifetime suicide attempt. Consistent and inconsistent reporters of lifetime suicide attempt did not differ on demographic or clinical variables with the exception of higher rates of lifetime suicidal ideation among consistent reporters (P < .001). Significant clinical differences were evident between inconsistent reporters and nonattempters. Conclusions Some level of inconsistent reporting of suicide attempt is inevitable when schools or health care systems systematically screen for suicide risk in adolescents. Inconsistent and consistent reporters of suicide attempt differ on few demographic or clinical variables; further prospective research should investigate the reasons for inconsistent reporting as well as the validity and stability of reporting in predicting future suicidal behavior.

  June 26, 2013   doi: 10.1002/da.22135   open full text
• Utility Of The Dimensions Of Anger Reactions–5 (Dar‐5) Scale As A Brief Anger Measure.
  David Forbes, Nathan Alkemade, Damon Mitchell, Jon D. Elhai, Tony McHugh, Glen Bates, Raymond W. Novaco, Richard Bryant, Virginia Lewis.
  Depression and Anxiety. June 25, 2013
  Background Anger is a common emotional sequel in the aftermath of traumatic experience. As it is associated with significant distress and influences recovery, anger requires routine screening and assessment. Most validated measures of anger are too lengthy for inclusion in self‐report batteries or as screening tools. This study examines the psychometric properties of a shortened 5‐item version of the Dimensions of Anger Reactions (DAR), an existing screening tool. Methods Responses to the DAR‐5 were analysed from a sample of 486 college students with and without a history of trauma exposure. Results The DAR‐5 demonstrated strong internal reliability and concurrent validity with the State Trait Anger Expression Inventory‐2 (STAXI‐2). Confirmatory factor analysis supported a single factor model of the DAR‐5 for the trauma‐exposed and nontrauma subsamples. A screening cut‐off point of 12 on the DAR‐5 successfully differentiated high and low scorers on STAXI‐2 Trait Anger and PCL posttraumatic stress scores. Further discriminant validity was found with depression symptom scores. Conclusions The results support use of the DAR‐5 for screening for anger when a short scale is required.

  June 25, 2013   doi: 10.1002/da.22148   open full text
• Trajectories Of Change In Anxiety Severity And Impairment During And After Treatment With Evidence‐Based Treatment For Multiple Anxiety Disorders In Primary Care.
  Jutta M. Joesch, Daniela Golinelli, Cathy D. Sherbourne, Greer Sullivan, Murray B. Stein, Michelle G. Craske, Peter P. Roy‐Byrne.
  Depression and Anxiety. June 25, 2013
  Background Coordinated Anxiety Learning and Management (CALM) is a model for delivering evidence‐based treatment for anxiety disorders in primary care. Compared to usual care, CALM produced greater improvement in anxiety symptoms. However, mean estimates can obscure heterogeneity in treatment response. This study aimed to identify (1) clusters of participants with similar patterns of change in anxiety severity and impairment (trajectory groups); and (2) characteristics that predict trajectory group membership. Methods The CALM randomized controlled effectiveness trial was conducted in 17 primary care clinics in four US cities in 2006–2009. 1,004 English‐ or Spanish‐speaking patients age 18–75 with panic, generalized anxiety, social anxiety, and/or posttraumatic stress disorder participated. The Overall Anxiety Severity and Impairment Scale was administered repeatedly to 482 participants randomized to CALM treatment. Group‐based trajectory modeling was applied to identify trajectory groups and multinomial logit to predict trajectory group membership. Results Two predicted trajectories, representing about two‐thirds of participants, were below the cut‐off for clinically significant anxiety a couple of months after treatment initiation. The predicted trajectory for the majority of remaining participants was below the cut‐off by 9 months. A small group of participants did not show consistent improvement. Being sicker at baseline, not working, and reporting less social support were associated with less favorable trajectories. Conclusions There is heterogeneity in patient response to anxiety treatment. Adverse circumstances appear to hamper treatment response. To what extent anxiety symptoms improve insufficiently because adverse patient circumstances contribute to suboptimal treatment delivery, suboptimal treatment adherence, or suboptimal treatment response requires further investigation.

  June 25, 2013   doi: 10.1002/da.22149   open full text
• Gaze Avoidance In Social Anxiety Disorder.
  Justin W. Weeks, Ashley N. Howell, Philippe R. Goldin.
  Depression and Anxiety. June 24, 2013
  Background The relationship between gaze avoidance and social anxiety has been examined previously using eye‐tracking and static social images. Overall, findings to date highlight increased gaze avoidance as a behavioral marker of social anxiety. The purpose of the present study was to better elucidate the relationship between gaze avoidance and social anxiety disorder (SAD) symptoms via covert eye tracking of gaze tendencies in response to a dynamic computerized social interaction simulation. On the basis of the bivalent fear of evaluation (BFOE) model of social anxiety,[1] it was expected that participants with SAD, compared to nonsocially anxious control (NSAC) participants, would exhibit gaze avoidance in response to both positive and negative social feedback. Methods Participants with SAD (n = 20), and a sample of demographically equivalent NSAC (n = 19), were administered clinical diagnostic interviews and a computerized social simulation task. The simulation task consisted of viewing 26 dynamic videos (13 positive and 13 negative), each 12 s in duration. All participants were covertly eye tracked during the simulation. Results SAD participants exhibited greater global gaze avoidance in response to both the positive and negative video clips in comparison to the controls. Moreover, the SAD group exhibited equivalent gaze avoidance in response to stimuli of both emotional valences. Conclusions These results provide additional support for gaze avoidance as a behavioral marker of SAD, as well as additional support for the BFOE model. Implications for the assessment of SAD are discussed.

  June 24, 2013   doi: 10.1002/da.22146   open full text
• Attention Bias To Threat Faces In Severe Mood Dysregulation.
  Rebecca E. Hommer, Allison Meyer, Joel Stoddard, Megan E. Connolly, Karin Mogg, Brendan P. Bradley, Daniel S. Pine, Ellen Leibenluft, Melissa A. Brotman.
  Depression and Anxiety. June 24, 2013
  Background We used a dot‐probe paradigm to examine attention bias toward threat (i.e., angry) and happy face stimuli in severe mood dysregulation (SMD) versus healthy comparison (HC) youth. The tendency to allocate attention to threat is well established in anxiety and other disorders of negative affect. SMD is characterized by the negative affect of irritability, and longitudinal studies suggest childhood irritability predicts adult anxiety and depression. Therefore, it is important to study pathophysiologic connections between irritability and anxiety disorders. Methods SMD patients (N = 74) and HC youth (N = 42) completed a visual probe paradigm to assess attention bias to emotional faces. Diagnostic interviews were conducted and measures of irritability and anxiety were obtained in patients. Results SMD youth differed from HC youth in having a bias toward threatening faces (P < .01). Threat bias was positively correlated with the severity of the SMD syndrome and depressive symptoms; degree of threat bias did not differ between SMD youth with and without co‐occurring anxiety disorders or depression. SMD and HC youth did not differ in bias toward or away from happy faces. Conclusions SMD youth demonstrate an attention bias toward threat, with greater threat bias associated with higher levels of SMD symptom severity. Our findings suggest that irritability may share a pathophysiological link with anxiety and depressive disorders. This finding suggests the value of exploring further whether attention bias modification treatments that are effective for anxiety are also helpful in the treatment of irritability.

  June 24, 2013   doi: 10.1002/da.22145   open full text
• Factors Impacting Decisions To Decline Or Adhere To Antidepressant Medication In Perinatal Women With Mood And Anxiety Disorders.
  Shaila Misri, Andrea B. Eng, Jasmin Abizadeh, Ekin Blackwell, Alicia Spidel, Tim F. Oberlander.
  Depression and Anxiety. June 18, 2013
  Purpose To identify specific quantitative and qualitative factors that govern the decision to adhere or decline antidepressant medication in antenatal women with moderate‐to‐severe mood and anxiety disorders. Methods Fifty women (30 adherers, 20 decliners) were recruited between 18 and 34 weeks gestation in a tertiary care clinic for perinatal mothers. They were prospectively monitored 4 weeks apart up to 1‐month postpartum on the: Hamilton Anxiety Scale, Hamilton Depression Scale, Mood Disorders Insight Scale, Antidepressant Compliance Questionnaire, Penn State Worry Questionnaire, and NEO Personality Inventory. Qualitative interviews were conducted at baseline. Hierarchical linear modeling determined illness trajectories of the two groups. Results Significantly different course of illness was observed in adherers versus decliners. Adherers had healthier attitudes toward depression and compliance with medication (P < .005). Decliners had less illness insight (P < .001) and cited fear of fetal exposure, and thought medication was unwarranted. Conclusions Pregnant women experienced significantly divergent illness trajectories depending on if they accepted antidepressant medication therapy for their illness. Risk perception, attitudes, and illness insight impacted decisions surrounding adherence and decline.

  June 18, 2013   doi: 10.1002/da.22137   open full text
• The Latent Structure And Comorbidity Patterns Of Generalized Anxiety Disorder And Major Depressive Disorder: A National Study.
  Carlos Blanco, José M. Rubio, Melanie Wall, Roberto Secades‐Villa, Katja Beesdo‐Baum, Shuai Wang.
  Depression and Anxiety. June 14, 2013
  Background There is controversy on whether generalized anxiety disorder (GAD) and major depressive disorder (MDD) constitute the same or separate disorders. This study sought to examine the factor structure of the DSM‐IV diagnostic criteria of GAD and MDD and the patterns of comorbidity associated with both disorders. Methods Data were drawn from the National Epidemiological Survey on Alcohol and Related conditions (NESARC), a representative sample of the adult general population in the United States (N = 43,093). Sociodemographic and psychiatric comorbidity correlates of GAD, MDD, and co‐occurring GAD‐MDD were obtained. Exploratory and confirmatory factor analyses of the DSM‐IV diagnostic criteria for GAD and MDD were conducted, followed by a Multiple Indicators Multiple Causes (MIMIC) model to examine the invariance of the model across several sociodemographic covariates. Results A bifactor model with one general factor underlying all the MDD and GAD diagnostic criteria and another factor with large loadings only for the GAD criteria best represented the latent structure. This model showed excellent fit indices (CFI = 1.00, TLI = 1.00, RMSEA < 0.02), and a high degree of invariance across sociodemographic covariates. The comorbidity patterns of individuals with MDD only (n = 4,885), GAD only (n = 947) and GAD‐MDD (n = 810) were clearly distinguishable. Conclusions The latent structure of the diagnostic criteria of MDD and GAD and their comorbidity patterns suggests that GAD and MDD are closely related but different nosological entities, with distinct latent structures, clinical manifestations, and patterns of comorbidity.

  June 14, 2013   doi: 10.1002/da.22139   open full text
• Maintenance Treatment With Quetiapine When Combined With Either Lithium Or Divalproex In Bipolar I Disorder: Analysis Of Two Large Randomized, Placebo‐Controlled Trials.
  Trisha Suppes, Eduard Vieta, Urban Gustafsson, Birgit Ekholm.
  Depression and Anxiety. June 12, 2013
  Background To determine the efficacy and safety of quetiapine combined with lithium or divalproex for preventing mood events in patients with bipolar I disorder. In this pooled analysis of two similar long‐term studies (D1447C00126 [NCT00107731] and D1447C00127 [NCT00081380]), lithium and divalproex treatment groups were analyzed separately. Methods Patients received open‐label quetiapine (400–800 mg/d) plus lithium or divalproex to achieve ≥12 weeks of clinical stability before being randomized to double‐blind combination treatment with quetiapine (400–800 mg/d) or placebo plus lithium or divalproex for up to 104 weeks. The primary endpoint was time to first mood event postrandomization following open stabilization. Results Of 3,414 patients in the stabilization phase, 1,326 were randomized. There were no differences in the risk of recurrence of mood, mania, or depression between quetiapine plus lithium or quetiapine plus divalproex. Among patients co‐treated with placebo and lithium, the risk of recurrence of a mania event was significantly higher than among patients co‐treated with placebo and divalproex. In patients with an index episode of mania, placebo plus lithium was associated with a significantly higher risk of recurrence of a mania event than placebo plus divalproex. Safety data were generally consistent with recognized safety profiles. Conclusions In patients with bipolar I disorder previously stabilized on quetiapine and lithium or divalproex, maintenance therapy with quetiapine significantly increased the time to recurrence of a mood event (mania or depression) versus placebo, regardless of whether it was combined with lithium or divalproex.

  June 12, 2013   doi: 10.1002/da.22136   open full text
• Gatekeeper Training For Suicide Prevention In First Nations Community Members: A Randomized Controlled Trial.
  Jitender Sareen, Corinne Isaak, Shay‐Lee Bolton, Murray W. Enns, Brenda Elias, Frank Deane, Garry Munro, Murray B. Stein, Dan Chateau, Madelyn Gould, Laurence Y. Katz.
  Depression and Anxiety. June 12, 2013
  Background Gatekeeper training aims to train people to recognize and identify those who are at risk for suicide and assist them in getting care. Applied Suicide Intervention Skills Training (ASIST), a form of gatekeeper training, has been implemented around the world without a controlled evaluation. We hypothesized that participants in 2 days of ASIST gatekeeper training would have increased knowledge and preparedness to help people with suicidal ideation in comparison to participants who received a 2‐day Resilience Retreat that did not focus on suicide awareness and intervention skills (control condition). Methods First Nations on reserve people in Northwestern Manitoba, aged 16 years and older, were recruited and randomized to two arms of the study. Self‐reported measures were collected at three time points—immediately pre‐, immediately post‐, and 6 months post intervention. The primary outcome was the Suicide Intervention Response Inventory, a validated scale that assesses the capacity for individuals to intervene with suicidal behavior. Secondary outcomes included self‐reported preparedness measures and gatekeeper behaviors. Results In comparison with the Resilience Retreat (n = 24), ASIST training (n = 31) was not associated with a significant impact on all outcomes of the study based on intention‐to‐treat analysis. There was a trend toward an increase in suicidal ideation among those who participated in the ASIST in comparison to those who were in the Resilience Retreat. Conclusions The lack of efficacy of ASIST in a First Nations on‐reserve sample is concerning in the context of widespread policies in Canada on the use of gatekeeper training in suicide prevention.

  June 12, 2013   doi: 10.1002/da.22141   open full text
• Apolipoprotein E Gene Polymorphism, Alcohol Use, And Their Interactions In Combat‐Related Posttraumatic Stress Disorder.
  Tae Yong Kim, Hae Gyung Chung, Han‐Sang Shin, Se Joo Kim, Jin Hee Choi, Moon Yong Chung, Suk Kyoon An, Tai Kiu Choi, Hyoung Seok So, Hyun‐Sang Cho.
  Depression and Anxiety. June 12, 2013
  Background The symptomatology of posttraumatic stress disorder (PTSD) is related not only to the intensity of the causative trauma, but also to alcohol use and genetic factors. Among the many candidate genes, the apolipoprotein E gene (APOE) is thought to be associated with stress reactivity. Methods Korean veterans of the Vietnam War with (n = 128) or without (n = 128) PTSD participated in this study. The Clinician‐Administered PTSD Scale and Combat Exposure Scale were administered, and the severity of alcohol use was assessed among these veterans. The APOE polymorphism and clinical variables of the subjects were compared, and associations between PTSD and potential explanatory variables were tested using logistic regression analysis. Results Higher frequencies of APOE ε2 alleles and a greater number of individuals with the ε2 allele were found in the PTSD group. Among patients with PTSD, ε2‐allele noncarriers consumed alcohol in greater amounts and more frequently than did ε2‐allele carriers. Regression analysis revealed a significant interactional effect between harmful drinking and the absence of the ε2 allele associated with PTSD risk. Conclusions These results suggest that the APOE ε2 allele operates as a susceptibility gene for combat‐related PTSD, with the relationship between alcohol use and PTSD differing according to the ε2‐allele status. Future studies should determine the role of the APOE in adaptation to extreme stress, the development of PTSD, and comorbid alcohol‐related disorders.

  June 12, 2013   doi: 10.1002/da.22138   open full text
• DIFFICULT‐TO‐TREAT PEDIATRIC OBSESSIVE‐COMPULSIVE DISORDER: FEASIBILITY AND PRELIMINARY RESULTS OF A RANDOMIZED PILOT TRIAL OF d‐CYCLOSERINE‐AUGMENTED BEHAVIOR THERAPY.
  Lara J. Farrell, Allison M. Waters, Mark J. Boschen, Laetitia Hattingh, Harry McConnell, Ella L. Milliner, Nigel Collings, Melanie Zimmer‐Gembeck, Doug Shelton, Thomas H. Ollendick, Chris Testa, Eric A. Storch.
  Depression and Anxiety. May 30, 2013
  Background This study examined the feasibility and preliminary effectiveness of d‐cycloserine (DCS)–augmented cognitive behavioral therapy (CBT) for children and adolescents with difficult‐to‐treat Obsessive Compulsive Disorder, in a double‐blind randomized controlled pilot trial (RCT). Methods Seventeen children and adolescents (aged 8–18 years) with a primary diagnosis of OCD, which was deemed difficult‐to‐treat, were randomly assigned to either nine sessions of CBT including five sessions of DCS‐augmented exposure and response prevention (ERP) [ERP + DCS] or nine sessions of CBT including five sessions of placebo‐augmented ERP [ERP + PBO]. Weight‐dependent DCS or placebo doses (25 or 50 mg) were taken 1 hour before ERP sessions. Results At posttreatment, both groups showed significant improvements with 94% of the entire sample classified as responders. However, a greater improvement in the ERP + DCS relative to the ERP + PBO condition was observed at 1‐month follow‐up on clinician‐rated obsessional severity and diagnostic severity, and parent ratings of OCD severity. There were no changes across time or condition from 1‐ to 3‐month follow‐up. Conclusions In this preliminary study, DCS‐augmented ERP produced significant improvements in OCD severity from posttreatment to 1‐month follow‐up, relative to a placebo control condition, in severe and difficult‐to‐treat pediatric OCD. The significant effect on obsessional severity suggests that DCS augmentation might be associated with enhanced modification of obsessional thoughts during ERP, and warrants further investigation.

  May 30, 2013   doi: 10.1002/da.22132   open full text
• Retention And Attrition Among African Americans In The Star*D Study: What Causes Research Volunteers To Stay Or Stray?
  Eleanor J. Murphy, Layla Kassem, Anat Chemerinski, A. John Rush, Gonzalo Laje, Francis J. McMahon.
  Depression and Anxiety. May 30, 2013
  Background High attrition rates among African‐Americans (AA) volunteers are a persistent problem that makes clinical trials less representative and complicates estimation of treatment outcomes. Many studies contrast AA with other ethnic/racial groups, but few compare the AA volunteers who remain in treatment with those who leave. Here, in addition to comparing patterns of attrition between African Americans and Whites, we identify predictors of overall and early attrition among African Americans. Method Sample comprised non‐Hispanic African‐American (n = 673) and White (n = 2,549) participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Chi‐square tests were used to examine racial group differences in reasons for exit. Multivariate logistic regression was used to examine predictors of overall attrition, early attrition (by level 2) and top reasons cited for attrition among African Americans. Results Both African‐American and White dropouts most commonly cited noncompliance reasons for attrition during the earlier phases of the study, while citing reasons related to efficacy and medication side effects later in the study. Satisfaction with treatment strongly predicted overall attrition among African Americans independent of socioeconomic, clinical, medical or psychosocial factors. Early attrition among African American dropouts was associated with less psychiatric comorbidity, and higher perceived physical functioning but greater severity of clinician‐rated depression. Conclusions Compliance, efficacy, and side effects are important factors that vary in relative importance during the course of a clinical trial. For African Americans in such trials, retention strategies should be broadened to emphasize patient engagement and satisfaction during the critical periods immediately following enrollment and treatment initiation.

  May 30, 2013   doi: 10.1002/da.22134   open full text
• Religiosity And Longitudinal Change In Psychosocial Functioning In Adult Offspring Of Depressed Parents At High Risk For Major Depression.
  Stephanie Kasen, Priya Wickramaratne, Marc J. Gameroff.
  Depression and Anxiety. May 29, 2013
  Background Recent findings suggest that beliefs about religious or spiritual importance or attending religious/spiritual services may protect high‐risk offspring against depression. This research has not extended to examining religiosity in relation to psychosocial functioning in high‐risk offspring. Methods Offspring selected for having a depressed parent and offspring of nondepressed parents were evaluated for lifetime major depressive disorder (MDD) in childhood and adolescence, and at 10‐year (T10) and 20‐year (T20) follow‐ups. Relations between self‐reported religiosity at T10 and longitudinal change in psychosocial function from T10 to T20 (assessed by clinical ratings on Global Assessment Scale [GAS]) were examined separately in 109 daughters and 76 sons by risk status. Results Lifetime MDD was diagnosed in 57.8% of daughters and 40.8% of sons by T20. Among daughters, only those with lifetime MDD showed improved psychosocial functioning in relation to higher level of service attendance at T10, their mean GAS score improving by 3.5 points (P = .018) over the next decade. For daughters with and without lifetime MDD, relations between higher levels of religiosity and improved psychosocial function were of greater magnitude in those with a depressed parent. Among sons, only those with lifetime MDD showed improved psychosocial function in relation to higher level of religious/spiritual importance, their mean GAS score improving by 4.6 points (P < .0001) over the next decade; that relation was of greater magnitude in sons with both lifetime MDD and a depressed parent. Conclusions Greater improvement in psychosocial functioning in relation to religious involvement in more vulnerable offspring supports religiosity as a resilience factor.

  May 29, 2013   doi: 10.1002/da.22131   open full text
• Self‐Attributed Seasonality Of Mood And Behavior: A Report From The Netherlands Study Of Depression And Anxiety.
  Wim H. Winthorst, Annelieke M. Roest, Elisabeth H. Bos, Ybe Meesters, Brenda W.J.H. Penninx, Willem A. Nolen, Peter Jonge.
  Depression and Anxiety. May 21, 2013
  Background Seasonal changes in mood and behavior are considered to be common in the general population and in patients with psychiatric disorders. However, in several studies this seasonality could not be demonstrated. The present study examined self‐attributed seasonality of depressive symptoms among patients with a lifetime diagnosis of a depressive disorder (D), an anxiety disorder (A), a comorbid depressive and anxiety disorder (DA), and healthy controls (HC). Methods The CIDI was used to establish diagnoses according to DSM‐IV criteria in 2,168 participants of the Netherlands Study of Depression and Anxiety (NESDA). The Seasonal Pattern Assessment Questionnaire (SPAQ) was administered to assess variation in mood and behavior. Results Of the 2,168 participants 53.5% reported seasonality of mood. Highest percentages of low mood were seen in the winter months. Although all groups showed this pattern of lowered mood during the winter months, D, A, and DA were significantly (P < .001) more likely to experience seasonality is this respect. This was also shown for seasonal changes in energy, social activities, sleeping, eating, weight and for the Global Seasonality Score. A limitation of this study was the cross‐sectional design. Conclusions Seasonal variation in mood and behavior was demonstrated for both participants with a lifetime diagnosis of depression and/or anxiety disorder and for healthy controls, but patients with anxiety and/or depression were more likely to experience this seasonal variation. Clinicians should take into account that the time of the year could influence the feelings of well‐ and ill‐being of their patients.

  May 21, 2013   doi: 10.1002/da.22130   open full text
• Relationship Between Sleep Disturbance And Depression, Anxiety, And Functioning In College Students.
  Maren Nyer, Amy Farabaugh, Kiki Fehling, David Soskin, Daphne Holt, George I. Papakostas, Paola Pedrelli, Maurizio Fava, Angela Pisoni, Ottavio Vitolo, David Mischoulon.
  Depression and Anxiety. May 16, 2013
  Background Sleep disturbance (SD) has complex associations with depression, both preceding and following the onset and recurrence of depression. We hypothesized that students with depressive symptoms with SD would demonstrate a greater burden of comorbid psychiatric symptoms and functional impairment compared to students with depressive symptoms without SD. Methods During a mental health screening, 287 undergraduate students endorsed symptoms of depression (Beck Depression Inventory [BDI] ≥ 13) and filled out the following self‐report measures: demographic questionnaire, BDI, Anxiety Symptom Questionnaire—intensity and frequency (ASQ), Beck Hopelessness Scale (BHS), Beck Anxiety Inventory (BAI), Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ), and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ). SD was measured using the BDI sleep item #16 dichotomized (score 0: no SD; or score > 0: some SD). Results Students with depressive symptoms and SD (n = 220), compared to those without SD (n = 67), endorsed significantly more intense and frequent anxiety and poorer cognitive and physical functioning. Students with depressive symptoms with and without SD did not significantly differ in depressive severity, hopelessness, or quality of life. Conclusions College students with depressive symptoms with SD may experience a greater burden of comorbid anxiety symptoms and hyperarousal, and may have impairments in functioning, compared to students with depressive symptoms without SD. These findings require replication.

  May 16, 2013   doi: 10.1002/da.22064   open full text
• Development Of A Guided Self‐Help (Gsh) Program For The Treatment Of Mild‐To‐Moderate Posttraumatic Stress Disorder (Ptsd).
  Catrin Lewis, Neil Roberts, Tracey Vick, Jonathan I. Bisson.
  Depression and Anxiety. May 13, 2013
  Background There is a shortage of suitably qualified therapists able to deliver evidence‐based treatment for posttraumatic stress disorder (PTSD), precluding timely access to intervention. This work aimed to develop an optimally effective, feasible, and acceptable guided self‐help (GSH) program for treatment of the disorder. Methods The study followed Medical Research Council (MRC) guidance for the development of a complex intervention. A prototype GSH program was developed through an initial modeling phase. Systematic reviews of the literature informed a portfolio of up‐to‐date information for key stakeholders to consider and discuss in a series of focus groups and semistructured interviews, which included 10 mental health professionals with expertise in the fields of GSH and/or PTSD, and seven former PTSD sufferers. Data were analyzed through a process of Inductive Thematic Analysis and used to inform the content, delivery, and guidance of a GSH program for PTSD. The prototype was piloted with 19 PTSD sufferers in two pilot studies, and refined on the basis of their quantitative results and qualitative feedback. Results The final version was available online and in hardcopy. It included 11 modules, some being mandatory and others optional, allowing tailoring of the intervention to meet an individual's specific needs. Qualitative and quantitative results of the pilot studies supported its efficacy in terms of reducing traumatic stress symptoms and its acceptability to PTSD sufferers. Conclusions Delivering psychological treatment in a GSH format shows promise as an effective and acceptable way of treating mild‐to‐moderate PTSD.

  May 13, 2013   doi: 10.1002/da.22128   open full text
• Augmentation Of Youth Cognitive Behavioral And Pharmacological Interventions With Attention Modification: A Preliminary Investigation.
  Bradley C. Riemann, Jennie M. Kuckertz, Michelle Rozenman, V. Robin Weersing, Nader Amir.
  Depression and Anxiety. May 08, 2013
  Background Recent research suggests the efficacy of attention modification programs (AMP) in treating adult anxiety.[1] Though some research supports the success of AMP treatment in anxious youths,[2, 3] to date no study has examined the efficacy of AMP as an adjunctive treatment to other psychosocial and pharmacological interventions for anxious youths within the community. Methods In the current study, we examined the efficacy of AMP as an adjunctive treatment to standard care at a residential anxiety treatment facility. Adolescents (N = 42) completed either an active (attention modification program, AMP; n = 21) or a control (attention control condition, ACC; n = 21) condition, in addition to the facility's standard treatment protocol, which included cognitive behavioral therapy with or without medication. Results While anxiety symptoms decreased for participants across both groups, participants in the AMP group experienced a significantly greater decrease in anxiety symptoms from point of intake to point of discharge, in comparison to participants in the ACC group. Conclusions These results suggest that AMP is an effective adjunctive treatment to the standard treatments of choice for anxiety disorders, and may hold promise for improving treatment response in highly anxious youths.

  May 08, 2013   doi: 10.1002/da.22127   open full text
• Smoking And Suicidality In Subjects With Bipolar Disorder: Results From The National Epidemiologic Survey On Alcohol And Related Conditions (Nesarc).
  Ji Hyun Baek, Lori R. Eisner, Andrew A. Nierenberg.
  Depression and Anxiety. May 08, 2013
  Background Smoking in patients with bipolar disorder is known to be related to suicidality. This link has not been investigated, however, in community‐based samples. The aim of this study is to delineate the sociodemographic and clinical characteristics of bipolar smokers and examine the relationship between these characteristics and suicidal ideation or attempts in an epidemiologic database, the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Methods Subjects (n = 1,643) with bipolar disorder I and II, defined by the DSM‐IV criteria, who had a history of low moods lasting more than 2 weeks were included in our analysis. Current smokers, former smokers, and lifetime nonsmokers were compared in terms of demographic, clinical characteristics, and functional level. Suicidality, evaluated by a history of suicide ideation and attempts while in low mood were compared. Results Current smokers with bipolar disorder showed a greater number of DSM‐IV symptoms while in acute episodes, higher rate of alcohol, and drug use disorders, as well as poorer functional levels than nonsmokers. Previous smokers displayed intermediate characteristics between current smokers and nonsmokers. The logistic regression analysis revealed that current smoking status predicted the risk of having a history of attempted suicide (Odds ratio 1.35, 95% CI: 1.05–1.76) after adjusting for age, sex, race, bipolar subtype, lifetime axis II/anxiety/alcohol use/substance use disorder; however, lifetime smoking status did not. Conclusions The present study confirms that current cigarette smoking can predict attempted suicide in a community representative sample of people with bipolar disorder.

  May 08, 2013   doi: 10.1002/da.22107   open full text
• Cognitive Behavioral Therapy Age Effects In Child And Adolescent Anxiety: An Individual Patient Data Metaanalysis.
  Kathryn Bennett, Katharina Manassis, Stephen D. Walter, Amy Cheung, Pamela Wilansky‐Traynor, Natalia Diaz‐Granados, Stephanie Duda, Maureen Rice, Susan Baer, Paula Barrett, Denise Bodden, Vanessa E. Cobham, Mark R. Dadds, Ellen Flannery‐Schroeder, Golda Ginsburg, David Heyne, Jennifer L. Hudson, Philip C. Kendall, Juliette Liber, Carrie Masia Warner, Sandra Mendlowitz, Maaike H. Nauta, Ronald M. Rapee, Wendy Silverman, Lynne Siqueland, Susan H. Spence, Elisabeth Utens, Jeffrey J. Wood.
  Depression and Anxiety. May 08, 2013
  Background Investigations of age effects on youth anxiety outcomes in randomized trials (RCTs) of cognitive behavior therapy (CBT) have failed to yield a clear result due to inadequate statistical power and methodologic weaknesses. We conducted an individual patient data metaanalysis to address this gap. Question Does age moderate CBT effect size, measured by a clinically and statistically significant interaction between age and CBT exposure? Methods All English language RCTs of CBT for anxiety in 6–19 year olds were identified using systematic review methods. Investigators of eligible trials were invited to submit their individual patient data. The anxiety disorder interview schedule (ADIS) primary diagnosis severity score was the primary outcome. Age effects were investigated using multilevel modeling to account for study level data clustering and random effects. Results Data from 17 of 23 eligible trials were obtained (74%); 16 studies and 1,171 (78%) cases were available for the analysis. No interaction between age and CBT exposure was found in a model containing age, sex, ADIS baseline severity score, and comorbid depression diagnosis (power ≥ 80%). Sensitivity analyses, including modeling age as both a categorical and continuous variable, revealed this result was robust. Conclusions Adolescents who receive CBT in efficacy research studies show benefits comparable to younger children. However, CBT protocol modifications routinely carried out by expert trial therapists may explain these findings. Adolescent CBT protocols are needed to facilitate the transportability of efficacy research effects to usual care settings where therapists may have less opportunity for CBT training and expertise development.

  May 08, 2013   doi: 10.1002/da.22099   open full text
• The Public's Knowledge And Beliefs About Obsessive Compulsive Disorder.
  Meredith E. Coles, Richard G. Heimberg, Barry D. Weiss.
  Depression and Anxiety. May 03, 2013
  Background Obsessive compulsive disorder (OCD) is a disabling condition associated with significant personal and societal burdens. Despite the availability of efficacious treatments, in most cases, the disorder remains unrecognized and untreated. Lack of knowledge (i.e. poor mental health literacy, MHL) regarding OCD may be an impediment to seeking treatment. Therefore, the current study assessed public knowledge and beliefs about OCD and examined factors influencing MHL. Methods Five hundred seventy‐seven US adults participated in a telephone survey. After hearing a vignette describing someone with OCD, participants’ MHL for OCD was assessed across three domains as follows: recognition of OCD, knowledge and beliefs about available help, and concerns about being negatively evaluated for reporting symptoms. Results The majority of participants (90.9%) reported that the symptoms were a cause for concern and that the person in the vignette should seek professional help (89.5%). However, only one‐third of respondents correctly labeled the disorder as OCD. More respondents were optimistic about the likely success of psychotherapy than medication, but primary care physicians were the most frequently reported source of professional help. Finally, less education, lower income, and being in an older cohort were associated with poorer recognition of OCD. Conclusions When presented with brief vignettes describing a person with OCD, most community members can recognize the benefits of seeking professional help. However, recognition of the disorder and knowledge of treatment options can be improved.

  May 03, 2013   doi: 10.1002/da.22080   open full text
• Role Of Maternal Childhood Trauma On Parenting Among Depressed Mothers Of Psychiatrically Ill Children.
  Maureen Zalewski, Jill M. Cyranowski, Yu Cheng, Holly A. Swartz.
  Depression and Anxiety. May 03, 2013
  Background Independently, maternal depression and maternal history of childhood abuse confer risk for impaired parenting. These associations may be compounded when depressed mothers with histories of childhood abuse are faced with the challenge of parenting offspring who themselves struggle with mental health problems. This study examined the relationships among maternal history of childhood abuse, maternal depression, and parenting style in the context of parenting a psychiatrically ill child, with an emphasis on examining maternal emotional abuse and neglect. We hypothesized that maternal childhood emotional abuse would be associated with maladaptive parenting strategies (lower levels of maternal acceptance and higher levels of psychological control), independent of maternal depression severity and other psychosocial risk factors. Method Ninety‐five mother‐child dyads (children ages 7–18) were recruited from child mental health centers where children were receiving treatment for at least one internalizing disorder. Participating mothers met DSM‐IV criteria for major depressive disorder. Mothers reported on their own childhood abuse histories and children reported on their mothers’ parenting. Results Regression analyses demonstrated that maternal childhood emotional abuse was associated with child reports of lower maternal acceptance and greater psychological control, controlling for maternal depression severity, and other psychosocial risk factors. Conclusions When treating psychiatrically ill children, it is important for a child's clinician to consider mothers’ childhood abuse histories in addition to their history of depression. These mothers appear to have additional barriers to effective parenting.

  May 03, 2013   doi: 10.1002/da.22116   open full text
• Treatment Of Posttraumatic Stress Disorder Reduces Suicidal Ideation.
  Jaimie L. Gradus, Michael K. Suvak, Blair E. Wisco, Brian P. Marx, Patricia A. Resick.
  Depression and Anxiety. May 01, 2013
  Background Suicide is a significant public health problem. Although various studies have found evidence of posttraumatic stress disorder (PTSD) as a risk factor for suicidal behaviors, no study has examined whether or not PTSD treatment decreases suicidal thoughts. This study aims to fill this gap in the literature by examining changes in suicidal ideation over the course of a randomized clinical trial, which compared two widely used treatments for PTSD—cognitive processing therapy (CPT) and prolonged exposure (PE). Methods Data from 163 trial participants over five time points (pre‐ and posttreatment, 3 and 9 months posttreatment, and 5–10 years posttreatment) were examined using multilevel growth curve analyses to determine if reductions in PTSD symptoms during treatment were associated with reductions in suicidal ideation. Major depression diagnosis and hopelessness were controlled. Results Suicidal ideation decreased sharply during treatment with continued, but more subtle decreases, during the follow‐up period. These decreases were associated with decreases in PTSD symptoms over the course of treatment. These associations were not accounted for by depression diagnoses at the start of the study or changes in hopelessness over the course of treatment. Conclusions Two widely used, effective treatments for PTSD reduce suicidal ideation. CPT exhibited a larger influence on suicidal ideation than PE, although the magnitude of the difference was small in size. Inclusion of PTSD screening and treatment could enhance suicide prevention efforts.

  May 01, 2013   doi: 10.1002/da.22117   open full text
• Intolerance Of Uncertainty As A Mediator Of The Relationship Between Perfectionism And Obsessive‐Compulsive Symptom Severity.
  Erin T. Reuther, Thompson E. Davis, Brittany M. Rudy, Whitney S. Jenkins, Sara E. Whiting, Anna C. May.
  Depression and Anxiety. April 22, 2013
  Background Intolerance of uncertainty (IU) and perfectionism have both been shown to predict severity of obsessive–compulsive disorder (OCD) symptoms in populations diagnosed with OCD, as well as analogue samples. According to cognitive models of OCD, symptoms are maintained by dysfunctional beliefs including IU and perfectionism. The purpose of the current study is to extend research on the cognitive theory of OCD by describing how dysfunctional thoughts interact with each other. Methods In an analogue sample for OCD (N = 475), undergraduate students completed measures online pertaining to IU (IU scale), perfectionism (Frost Multidimensional Perfectionism Scale), and OCD symptoms and severity (Florida Obsessive–Compulsive Inventory). Results The proposed model of IU fully mediating the relationship between perfectionism and OCD severity was supported using structural equation modeling (SEM) analysis. Bootstrapping testing within AMOS 20 and Sobel tests further corroborated full mediation. Conclusions Results from the current study suggest that IU fully mediates the relationship between perfectionism and severity of OCD symptoms. This finding has an impact for understanding the nature and treatment of OCD with perfectionism as a primary symptom. Findings suggest that in order to address perfectionism, it is necessary to first treat cognitions and obsessions associated with IU and that this practice would lessen distress and interference associated with perfectionistic obsessions.

  April 22, 2013   doi: 10.1002/da.22100   open full text
• Is Adhd In Childhood Associated With Lifetime Hoarding Symptoms? An Epidemiological Study.
  Miquel A. Fullana, Gemma Vilagut, David Mataix‐Cols, Núria Duran Adroher, Ronny Bruffaerts, Brendan Bunting, Jose M. Caldas Almeida, Silvia Florescu, Giovanni Girolamo, Ron Graaf, Josep M. Haro, Viviane Kovess, Jordi Alonso.
  Depression and Anxiety. April 19, 2013
  Background Although hoarding symptoms have been traditionally conceptualized as part of obsessive‐compulsive disorder (OCD), recent data suggest that they may be more closely related to attention‐deficit hyperactivity (ADHD) symptoms and, in particular, inattention. The aim of the present epidemiological study was to investigate the association between retrospectively reported ADHD symptoms in childhood and lifetime hoarding symptoms. Methods Retrospectively reported childhood ADHD, and lifetime hoarding and obsessive‐compulsive symptoms were assessed with the Composite International Diagnostic Interview 3.0 in a random subsample of individuals (n = 2,963) participating in a cross‐sectional survey of the adult general population of nine European countries, as part of the World Mental Health (WMH) Surveys. Results Lifetime hoarding symptoms were more common among individuals with childhood ADHD symptoms than those without ADHD symptoms (8.9% versus 2.7%, P = 0.024). Childhood inattention (but not hyperactivity) was associated with lifetime hoarding symptoms (OR = 6.04, 95% CI = 3.59–10.1) and this association remained significant after controlling for the presence of obsessive‐compulsive symptoms. Conclusion Longitudinal studies are now needed to explore the hypothesis that inattention symptoms in childhood may be a precursor of hoarding difficulties later in life.

  April 19, 2013   doi: 10.1002/da.22123   open full text
• Cortisol Reactivity To Experimentally Manipulated Psychosocial Stress In Young Adults At Varied Risk For Depression.
  Matthew C. Morris, Uma Rao, Lily Wang, Judy Garber.
  Depression and Anxiety. April 19, 2013
  This study examined cortisol and affective reactivity to a psychosocial stress task in 102 young adults who varied in risk for depression (56 remitted depressed, 46 never depressed). Participants were randomly assigned to either a stress (i.e., social‐evaluative threat) or control (i.e., no social‐evaluative threat) condition. For never‐depressed individuals, cortisol responses were significantly greater in the stress compared to the control condition. Moreover, cortisol responses were significantly greater for never‐depressed than remitted‐depressed individuals in the stress condition. For individuals with a history of depression, cortisol responses did not differ significantly between the stress and control conditions. Negative affective reactivity also was higher for never depressed, but not remitted depressed, individuals in the stress compared to the control condition. Moreover, cortisol responses were inversely related to negative affect during the recovery phase in both stress and control conditions. Findings indicate the lack of a robust cortisol response to social evaluation stress among remitted‐depressed individuals as compared to that of never‐depressed controls. Future studies should investigate unique and interactive links between these hypothalamic‐pituitary‐adrenal and affective reactivity alterations and risk for subsequent depressive episodes.

  April 19, 2013   doi: 10.1002/da.22125   open full text
• The Effectiveness Of Booster Sessions In Cbt Treatment For Child And Adolescent Mood And Anxiety Disorders.
  Robin E. Gearing, Craig S. J. Schwalbe, RaeHyuck Lee, Kimberly E. Hoagwood.
  Depression and Anxiety. April 17, 2013
  Background To investigate the effects of booster sessions in cognitive behavioral therapy (CBT) for children and adolescents with mood or anxiety disorders, whereas controlling for youth demographics (e.g., gender, age), primary diagnosis, and intervention characteristics (e.g., treatment modality, number of sessions). Methods Electronic databases were searched for CBT interventions for youth with mood and anxiety disorders. Fifty‐three (k = 53) studies investigating 1,937 youth met criteria for inclusion. Booster sessions were examined using two case‐controlled effect sizes: pre–post and pre–follow‐up (6 months) effect sizes and employing weighted least squares (WLSs) regressions. Results Meta‐analyses found pre–post studies with booster sessions had a larger effect size r = .58 (k = 15; 95% CI = 0.52–0.65; P < .01) than those without booster sessions r = .45 (k = 38; 95% CI = 0.41–0.49; P < .001). In the WLS regression analyses, controlling for demographic factors, primary diagnosis, and intervention characteristics, studies with booster sessions showed larger pre–post effect sizes than those without booster sessions (B = 0.13, P < .10). Similarly, pre–follow‐up studies with booster sessions showed a larger effect size r = .64 (k = 10; 95% CI = 0.57–0.70; P < .10) than those without booster sessions r = .48 (k = 20; 95% CI = 0.42–0.53; P < .01). Also, in the WLS regression analyses, pre–follow‐up studies showed larger effect sizes than those without booster sessions (B = 0.08, P < .01) after accounting for all control variables. Conclusions Result suggests that CBT interventions with booster sessions are more effective and the effect is more sustainable for youth managing mood or anxiety disorders than CBT interventions without booster sessions.

  April 17, 2013   doi: 10.1002/da.22118   open full text
• Developmental Timing Of Child Maltreatment And Symptoms Of Depression And Suicidal Ideation In Young Adulthood: Results From The National Longitudinal Study Of Adolescent Health.
  Erin C. Dunn, Katie A. McLaughlin, Natalie Slopen, Jonathan Rosand, Jordan W. Smoller.
  Depression and Anxiety. April 16, 2013
  Background Child maltreatment is a potent risk factor for psychopathology. Although the developmental timing of first exposure to maltreatment is considered important in shaping risk of future psychopathology, no consensus exists on whether earlier or later exposures are more deleterious. This study examines whether age at first exposure to abuse is associated with subsequent depression and suicidal ideation. Methods Data were drawn from the National Longitudinal Study of Adolescent Health (n = 15,701). Timing of first maltreatment exposure was classified using: (1) a crude measure capturing early childhood (ages 0–5), middle childhood (ages 6–10), or adolescence (ages 11–17); and (2) a refined measure capturing infancy (ages 0–2), preschool (ages 3–5), latency (ages 6–8), prepubertal (ages 9–10), pubertal (ages 11–13), or adolescence (ages 14–17). We examined whether timing of first exposure was associated with depression and suicidal ideation in early adulthood in the entire sample and among those exposed to maltreatment. Results Respondents exposed to abuse, particularly physical abuse, at any age had a higher odds of depression and suicidal ideation in young adulthood than nonmaltreated respondents. Among maltreated respondents, exposure during early childhood (ages 0–5), particularly preschool (ages 3–5), was most strongly associated with depression. Respondents first exposed to physical abuse during preschool had a 77% increase in the odds of depression and those first exposed to sexual abuse during early childhood had a 146% increase in the odds of suicidal ideation compared to respondents maltreated as adolescents. Conclusions Developmental timing of first exposure to maltreatment influences risk for depression and suicidal ideation. Whether these findings are evidence for biologically based sensitive periods requires further study.

  April 16, 2013   doi: 10.1002/da.22102   open full text
• Extreme Obesity Is Associated With Suicidal Behavior And Suicide Attempts In Adults: Results Of A Population‐Based Representative Sample.
  Birgit Wagner, Grit Klinitzke, Elmar Brähler, Anette Kersting.
  Depression and Anxiety. April 10, 2013
  Objective A number of studies have revealed that the number of completed suicides decreases with increasing body mass index (BMI). However, only few studies have evaluated the association between suicidal behavior, suicide attempts, and the various BMI categories. The aim of this study was to determine whether obesity is positively associated with increased suicide attempts and suicidal behavior with consideration of gender differences. Methods In a representative German population‐based sample (N = 2436), interviews were conducted in 2011 to examine the prevalence of suicide attempts and suicidal behavior in participants in the different BMI categories. Logistic regression analyses were conducted for suicidal behavior and suicide attempts to examine the association between obesity status and suicidality, controlling for confounding variables. Suicidal behavior was assessed by the Suicidal Behaviors Questionnaire‐Revised (SBQ‐R), which is a four‐item self‐report measure of suicidal thoughts and past attempts. BMI was calculated from participants’ self‐reported height and weight. Results Analyses revealed that extremely obese participants (BMI ≥ 40.0) had a prevalence rate of suicidal behavior of 33% for female respondents and 13% for male respondents and rates for suicide attempts of 27% for female and 13% for male respondents. No significant gender differences could be found for any of the weight categories. Furthermore, adjusted odd ratios (AOR) showed a significant difference in suicidal behavior in class I obesity (OR, 3.02 [1.50–6.08] and class III obesity (OR, 21.22 [6.51–69.20]. AORs for suicide attempts showed significantly greater odds for class I obesity (OR, 3.49 [1.76–6.90] and class III obesity (OR, 12.43 [3.87–39.86] compared to the normal weight group. Conclusion These results support a positive relationship between suicidal behavior, suicide attempts, and obesity. However contrary to previous findings, no gender differences were found. The findings support the introduction of routine screening for suicidal behavior in extreme obese individuals.

  April 10, 2013   doi: 10.1002/da.22105   open full text
• Depressive Disorders Among Children In The Transforming China: An Epidemiological Survey Of Prevalence, Correlates, And Service Use.
  Bao‐liang Zhong, Jun Ding, Hong‐hui Chen, Yi Li, Han‐ming Xu, Jun Tong, An‐qi Wang, Guang‐zong Tang, Jia‐sheng Zhu, Dong‐quan Yang, Bo Liu, Qiang Wang, Wu‐fu Cheng, E. Yin, Mei‐jun Xu, Tao Zhang, Tian‐ming Hu, Xiao‐wei Feng, Hui Li, Tang‐qun Dan, Gang‐ming Cheng, Jian‐fang Zhang, Hong‐jie Li, Jun‐hong Zhu.
  Depression and Anxiety. April 03, 2013
  Background To date, no one‐phase survey of childhood depression has been performed in China that involves both urban and rural community children. The objective of this study was to determine the prevalence, correlates, and mental health service utilization of depressive disorders (DDs) in a community‐based sample of 6–14‐year‐old children in south‐central China. Methods Children (3,582) were approached through multistage sampling and interviewed using a Chinese version of the Mini International Neuropsychiatric Interview for Children and Adolescents 5.0, which is a structured interview that is administered by trained psychiatrists to obtain information from children and their guardians. Results The overall prevalence of all current DDs was found to be 2.8% (95%CI: 1.5–3.9). The risk factors for depression included being 9–14‐year old, not attending school, having unmarried parents, living in a nonnuclear family (single parent or parentless family), being taken care of by people other than two parents (single parent, grandparent(s), other relatives, or others) during the past year, and not being breastfed prior to 1 year of age. Only 5.8% of the depressed children had received professional help prior to the interview. Conclusions The prevalence of DDs among children in this part of China is relatively high compared with most figures reported in other countries. Depression in this age group has been a major public health concern, but it is often underrecognized. There is an urgent need to develop efficacious interventions aimed at the prevention and early recognition of childhood depression.

  April 03, 2013   doi: 10.1002/da.22109   open full text
• Effects Of Nicotine Withdrawal On Panic‐Like Response To Breath Holding: A Placebo‐Controlled, Double‐Blind, Crossover Patch Study.
  Fiammetta Cosci, Giuly Bertoli, Kenneth Abrams.
  Depression and Anxiety. April 03, 2013
  Background Cigarette smoking may increase the likelihood of developing panic disorder. Periods of nicotine withdrawal, in particular, may promote panic in individuals high in anxiety sensitivity. We examined the importance of nicotine withdrawal in the occurrence of smoking and panic. Methods We utilized a placebo‐controlled, double‐blind, randomized, crossover design. Fifty smokers underwent a breath‐holding (BH) challenge after the transdermal administration of nicotine on one test day and a placebo on another test day. Physiological and psychological variables were assessed at baseline as well as directly before and after the challenges. Results Nicotine abstinence induced a decrease in heart rate and systolic blood pressure (BP) before the BH procedure (heart rate: 78.80 ± 11.43 under nicotine, 70.88 ± 10.83 under placebo; systolic BP: 124.90 ± 11.34 under nicotine, 121.18 ± 13.44 under placebo) and shorter BH duration relative to the nicotine patch condition. Nicotine abstinence did not, though, increase fear reactivity to the challenge. Conclusions The findings for heart rate and BP are consistent with the stimulant properties of nicotine. The reduced capacity to maintain apnea under placebo might be due to carbon dioxide (CO2) hypersensitivity during periods of nicotine abstinence. The negative findings regarding fear reactivity might be due to BH being a relatively weak anxiogen. Future researchers are encouraged to employ CO2‐inhalation procedures to study the relationship between nicotine withdrawal and panic.

  April 03, 2013   doi: 10.1002/da.22113   open full text
• Social Anxiety In Physical Activity Participation In Patients With Mental Illness: A Cross‐Sectional Multicenter Study.
  Amber Herdt, Jan Knapen, Davy Vancampfort, Marc Hert, Emanuel Brunner, Michel Probst.
  Depression and Anxiety. March 26, 2013
  Background Social anxiety (SA) is a frequent comorbid condition in patients with mental illness. However, no data exist regarding SA in physical activity (PA) situations. The aim of the present study was to measure the level of self‐reported SA in PA participation in patients with mental illness compared to healthy controls. Methods Six hundred ninety‐three patients with mental illness and 2,888 controls aged between 18 and 65 years completed the Physical Activity and Sport Anxiety Scale (PASAS). Group and gender differences in PASAS scores were tested by ANOVA and Scheffé's post hoc test. Results After controlling for gender (P < .05), the patient group (men 40.2 ± 14.4; women 49.2 ± 17) scored higher on the PASAS compared to control group (men 30.6 ± 12.2; women 37.3 ± 13.7). Within both groups, women reported higher levels of SA compared to men. Conclusions Our data indicate that patients with mental illness reported higher levels of SA in PA situations compared to healthy control subjects. Health professionals should consider SA when trying to improve outcome and adherence of patients with mental illness to PA interventions.

  March 26, 2013   doi: 10.1002/da.22059   open full text
• Sexual Obsessions In Pediatric Obsessive‐Compulsive Disorder: Clinical Characteristics And Treatment Outcomes.
  Lorena Fernández de la Cruz, Faye Barrow, Koen Bolhuis, Georgina Krebs, Chloe Volz, Eriko Nakatani, Isobel Heyman, David Mataix‐Cols.
  Depression and Anxiety. March 26, 2013
  Background Sexual obsessions are common in adults with obsessive‐compulsive disorder (OCD), cause great distress, and are sometimes misinterpreted as indicating risk to others. Little is known about the prevalence, clinical correlates, and prognosis of such symptoms in young people. Methods Three hundred and eighty‐three patients referred to a specialist pediatric OCD clinic were administered a series of measures at intake and, for those treated at the clinic, again after treatment. Patients with and without sexual obsessions were compared on socio‐demographic and clinical characteristics. Mixed model analyses of variance compared treatment outcomes in both groups. Results A quarter of patients had sexual obsessions at baseline (age range 8–17); they had slightly more severe OCD symptoms and were more depressed than those without sexual obsessions. Aggressive and religious obsessions, magical thinking, fear of saying certain things, repeating rituals, superstitious games, mental rituals, and the need to tell, ask, or confess were more frequent in participants with sexual obsessions. Crucially, no differences in treatment outcome were found between the groups. Conclusions Sexual obsessions are common in pediatric OCD, even in very young children. Although they may be associated with particular clinical features, they do not interfere with treatment response. The occurrence of sexual obsessions in children should be recognized and these symptoms understood as ordinary, nonthreatening OCD symptoms, which pose no risk to others. They respond to the standard treatment strategies, so children and families should receive the usual message of optimism regarding the chances of recovery.

  March 26, 2013   doi: 10.1002/da.22097   open full text
• Long‐Term Outcome In Adults With Obsessive‐Compulsive Disorder.
  Michael H. Bloch, Christy Green, Stephen A. Kichuk, Philip A. Dombrowski, Suzanne Wasylink, Eileen Billingslea, Angeli Landeros‐Weisenberger, Benjamin Kelmendi, Wayne K. Goodman, James F. Leckman, Vladimir Coric, Christopher Pittenger.
  Depression and Anxiety. March 26, 2013
  Background Obsessive‐compulsive disorder (OCD) is a chronic condition that often produces lifelong morbidity, but few studies have examined long‐term outcome (greater than 5 years) in adult patients. Available studies suggest that 32–74% of adult OCD patients will experience clinical improvement over the long term. However, these studies were conducted before validated OCD rating scales were established and the development of evidence‐based treatments for OCD. Methods We investigated the 10–20 year outcome of 83 of 165 eligible subjects previously enrolled after participation in placebo‐controlled trials of serotonin reuptake inhibitor (SRI) medications for OCD. We examined the association between clinical characteristics at initial assessment and OCD symptom severity at follow‐up. We hypothesized that primary OCD symptom dimension and initial response to pharmacotherapy with serotonin reuptake inhibitors would be associated with later symptom severity. Results Only 20% (17 of 83) of subjects had experienced a remission of their OCD symptoms at follow‐up (Y‐BOCS ≤ 8). Forty‐nine percent (41 of 83) of subjects were still experiencing clinically significant OCD symptoms. Response to initial SRI pharmacotherapy was significantly associated with long‐term outcome: 31% (13 of 42) of subjects who responded (CGI < 3) to initial SRI pharmacotherapy were remitted at follow‐up, compared to 12% (3 of 25) of partial responders and none of the 16 subjects who had no response to initial SRI pharmacotherapy. We did not find a significant association between long‐term clinical outcome and any of the OCD symptom dimensions. Conclusion Despite the introduction and dissemination of several evidence‐based treatments for OCD, most adult OCD patients do not achieve remission. Initial response to pharmacotherapy was strongly associated with long‐term outcome.

  March 26, 2013   doi: 10.1002/da.22103   open full text
• Decreased Brainstem And Putamen Sert Binding Potential In Depressed Suicide Attempters Using [11 C]‐Zient Pet Imaging.
  Jonathon A. Nye, David Purselle, Christophe Plisson, Ronald J. Voll, Jeffrey S. Stehouwer, John R. Votaw, Clinton D. Kilts, Mark M. Goodman, Charles B. Nemeroff.
  Depression and Anxiety. March 22, 2013
  Background Deficits in serotonergic neurotransmission have been implicated in the pathogenesis of depression and suicidality. The present study utilized a novel positron‐emission tomography (PET) ligand to quantitate and compare brain regional serotonin transporter (SERT) binding potential in depressed patients with a past history of suicide attempts to that of healthy comparison subjects. Method We used [11C]‐ZIENT PET to label SERT in the serotonergic cell body rich brainstem, and forebrain projection fields. Quantitative PET emission data from 21 adults (10 healthy controls and 11 drug‐free patients with major depression) was used for group comparison. SERT binding potential (BPND) in eight MRI‐based brain regions of interest (ROI) were compared in high‐resolution PET images. Results SERT binding potential was significantly decreased in the midbrain/pons (P = .029) and putamen (P = .04) of depressed patients with a past suicide attempt relative to comparison subjects. Forebrain SERT binding was also reduced in the patient sample, though these region effects did not survive a multiple comparison correction. Conclusion These results suggest that decreased availability of the brainstem and basal ganglia SERT represents a biomarker of depression and thus confirm and extend the role of dysregulation of brain serotonergic neurotransmission in the pathophysiology of depression and suicide.

  March 22, 2013   doi: 10.1002/da.22049   open full text
• Comparison Of Behavioral Profiles For Anxiety‐Related Comorbidities Including Adhd And Selective Mutism In Children.
  Tal Levin‐Decanini, Sucheta D. Connolly, David Simpson, Liza Suarez, Suma Jacob.
  Depression and Anxiety. March 22, 2013
  Background Elucidating differences in social‐behavioral profiles of children with comorbid presentations, utilizing caregiver as well as teacher reports, will refine our understanding of how contextual symptoms vary across anxiety‐related disorders. Methods In our pediatric anxiety clinic, the most frequent diagnoses and comorbidities were mixed anxiety (MA; ≥ 1 anxiety disorder; N = 155), anxiety with comorbid attention‐deficit hyperactivity disorder (MA/ADHD, N = 47) and selective mutism (SM, N = 48). Behavioral measures (CPRS, CTRS) were analyzed using multiple one‐way multivariate analyses of covariance tests. Differences between the three diagnostic groups were examined using completed parent and teacher reports (N = 135, 46, and 48 for MA, MA/ADHD, and SM groups, respectively). Results Comparisons across the MA, MA/ADHD, and SM groups indicate a significant multivariate main effect of group for caregiver and teacher responses (P < 0.01). Caregivers reported that children with SM are similar in profile to those with MA, and both groups were significantly different from the MA/ADHD group. Teachers reported that children with SM had more problems with social behaviors than with the MA or MA/ADHD groups. Further comparison indicates a significant main effect of group (P < 0.001), such that children with SM have the greatest differences in behavior observed by teachers versus caregivers. Conclusions Clinical profiles between MA/ADHD, MA, and SM groups varied, illustrating the importance of multi‐rater assessment scales to capture subtle distinctions and to inform treatment planning given that comorbidities occur frequently in children who present with anxiety.

  March 22, 2013   doi: 10.1002/da.22094   open full text
• Evaluation Of The Proposed Social Anxiety Disorder Specifier Change For Dsm‐5 In A Treatment‐Seeking Sample Of Anxious Youth.
  Caroline E. Kerns, Jonathan S. Comer, Donna B. Pincus, Stefan G. Hofmann.
  Depression and Anxiety. March 14, 2013
  Background The current proposal for the DSM‐5 definition of social anxiety disorder (SAD) is to replace the DSM‐IV generalized subtype specifier with one that specifies fears in performance situations only. Relevant evaluations to support this change in youth samples are sparse. Methods The present study examined rates and correlates of the DSM‐IV and proposed DSM‐5 specifiers in a sample of treatment‐seeking children and adolescents with SAD (N = 204). Results When applying DSM‐IV subtypes, 64.2% of the sample was classified as having a generalized subtype of SAD, with the remaining 35.2% classifying as having a nongeneralized subtype SAD. Youth with generalized SAD, relative to those with nongeneralized SAD, were older, had more clinically severe SAD, showed greater depressive symptoms, and were more likely to have a comorbid depressive disorder. No children in the current sample endorsed discrete fear in performance situations only in the absence of fear in other social situations. Conclusions The present findings call into question the meaningfulness of the proposed changes in treatment‐seeking youth with SAD.

  March 14, 2013   doi: 10.1002/da.22067   open full text
• Anxiety Symptoms As Precursors Of Major Depression And Suicidal Ideation.
  Philip J. Batterham, Helen Christensen, Alison L. Calear.
  Depression and Anxiety. March 14, 2013
  Background Relative to depression symptoms, the role of anxiety symptoms in the development of depression and suicidal ideation has not been well established. This study aimed to identify the anxiety and depression symptoms that confer the greatest amount of risk for depression and suicidal ideation at the population level. Method The PATH through Life study is an Australian community‐based longitudinal cohort study of 7,485 younger, middle‐aged, and older adults. Adjusted population attributable risk (PAR) for incident depression and suicidal ideation after 4 years was assessed for 18 symptoms of anxiety and depression. Results Anxiety symptoms contributed greater risk overall to both depression (45%) and suicidal ideation (23%) incidence than depression symptoms (35% and 16%, respectively). Anxiety symptoms had largest PARs among younger age groups. Conclusions Prevention programs for depression and suicide should aim to reduce anxiety symptoms in addition to depression symptoms, and target individuals reporting symptoms such as worrying or irritability.

  March 14, 2013   doi: 10.1002/da.22066   open full text
• Association Of Mental Health Problems With Gastrointestinal Disorders In Iraq And Afghanistan Veterans.
  Shira Maguen, Erin Madden, Beth Cohen, Daniel Bertenthal, Karen Seal.
  Depression and Anxiety. March 14, 2013
  Background Gastrointestinal disorders (GIDs) represent a large public health burden, affecting an estimated 60–70 million Americans annually. Our goal was to examine the relationship between GID and the most common mental health disorders in a national group of newly returning veterans. We also evaluated gender differences in the association of mental health disorders and GID. Methods We utilized a retrospective, longitudinal cohort analysis of veterans’ health records. Participants were 603,221 Iraq and Afghanistan veterans who were new users of VA healthcare from October 7, 2001 (start of the war in Afghanistan) to December 31, 2010. Results The prevalence of GID in newly returning veterans was nearly 20%, and veterans with a mental health disorder were at least twice as likely to have a GID as those without mental health disorders. For women, the increased risk of all GIDs was greatest among those with depression. Among men, the increased risk of irritable bowel syndrome (IBS) was greatest among those with posttraumatic stress disorder. IBS was the GID most strongly associated with mental health conditions among both genders. Conclusions The large proportion of newly returning veterans with GIDs and comorbid mental health diagnoses is concerning. Successful detection and treatment of GIDs associated with mental health disorders will require integrated efforts from primary care and mental health.

  March 14, 2013   doi: 10.1002/da.22072   open full text
• Lethal Means Restriction For Suicide Prevention: Beliefs And Behaviors Of Emergency Department Providers.
  Marian E. Betz, Matthew Miller, Catherine Barber, Ivan Miller, Ashley F. Sullivan, Carlos A. Camargo, Edwin D. Boudreaux,.
  Depression and Anxiety. March 14, 2013
  Background We sought to examine the beliefs and behaviors of emergency department (ED) providers related to preventing suicide by reducing suicidal patients’ access to lethal methods (means restriction) and identify characteristics associated with asking patients about firearm access. Methods Physicians and nurses at eight EDs completed a confidential, voluntary survey. Results The response rate was 79% (n = 631); 57% of respondents were females and 49% were nurses. Less than half believed, “most” or “all” suicides are preventable. More nurses (67%) than physicians (44%) thought “most” or “all” firearm suicide decedents would have died by another method had a firearm been unavailable (P < .001). The proportion of providers who reported they “almost always” ask suicidal patients about firearm access varied across five patient scenarios: suicidal with firearm suicide plan (64%), suicidal with no suicide plan (22%), suicidal with nonfirearm plan (21%), suicidal in past month but not today (16%), and overdosed but no longer suicidal (9%). In multivariable logistic regression, physicians were more likely than nurses to “almost always” or “often” ask about a firearm across all five scenarios, as were older providers and those who believed their own provider type was responsible for assessing firearm access. Conclusions Many ED providers are skeptical about the preventability of suicide and the effectiveness of means restriction, and most do not assess suicidal patients’ firearm access except when a patient has a firearm suicide plan. These findings suggest the need for targeted staff education concerning means restriction for suicide prevention.

  March 14, 2013   doi: 10.1002/da.22075   open full text
• Impact Of Childhood Adversity On The Course And Suicidality Of Depressive Disorders: The Crescend Study.
  Sung‐Wan Kim, Hee‐Ju Kang, Seon‐Young Kim, Jae‐Min Kim, Jin‐Sang Yoon, Sung‐Won Jung, Min‐Soo Lee, Hyeon‐Woo Yim, Tae‐Youn Jun.
  Depression and Anxiety. March 11, 2013
  Objective The impact of childhood adversity persists across the life course. This study aimed to investigate the associations of childhood adversity with the course, suicidality, and treatment outcomes of depressive disorders. Method A total of 919 people with depressive disorders were recruited. Childhood adversities (≤12 years old) were ascertained using a checklist, in sexual abuse, physical abuse by parents, and separation of parents. Various assessment scales were administered at baseline and over 12 weeks of antidepressants treatment. Results All three forms of childhood adversity were associated with an increased likelihood of experiencing more current stressful events. Scores on the Beck Depression Inventory and Hamilton Anxiety Rating Scale were significantly higher in participants with a history of sexual abuse. Scores on the Beck Depression Inventory, Hamilton Depression Rating Scale, and Perceived Stress Scale were significantly higher, and scores on the WHO Quality of life instrument were significantly lower in participants with a history of physical abuse by parents. They were more likely to receive augmentation and combination treatment after the initial antidepressant treatment, whereas overall response rates to treatment did not differ. Scores on the Beck Scale for suicide ideation were significantly higher after treatment and/or at baseline in patients with sexual or physical abuse. Physical illness was more prevalent in individuals with physical abuse by parents or separation of parents. Conclusions Depressive patients with a history of childhood adversities had more severe and chronic forms of depression with high suicidality. More intensive treatment with particular clinical attention is indicated for this special population.

  March 11, 2013   doi: 10.1002/da.22088   open full text
• Complicated Grief Symptoms In Anxiety Disorders: Prevalence And Associated Impairment.
  Luana Marques, Eric Bui, Nicole LeBlanc, Eliora Porter, Donald Robinaugh, M. Taylor Dryman, Mireya Nadal‐Vicens, John Worthington, Naomi Simon.
  Depression and Anxiety. March 11, 2013
  Background Previous research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD. Methods Participants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM‐IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19‐item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of ≥30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q‐LES‐Q) and the Range of Impaired Functioning Tool (LIFE‐RIFT), respectively. Results Participants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher's Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life (β = −0.140, P = 0.023) and greater impairment (β = 0.141, P = 0.035) among individuals with AD. Conclusions Our findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted.

  March 11, 2013   doi: 10.1002/da.22093   open full text
• Neuroanatomic Abnormalities In Adolescents With Generalized Anxiety Disorder: A Voxel‐Based Morphometry Study.
  Jeffrey R. Strawn, Anna M. Wehry, Wen‐Jang Chu, Caleb M. Adler, James C. Eliassen, Michael A. Cerullo, Stephen M. Strakowski, Melissa P. DelBello.
  Depression and Anxiety. March 11, 2013
  Background Despite recent data implicating functional abnormalities in the neurocircuitry underlying emotional processing in pediatric anxiety disorders, little is known regarding neurostructural abnormalities within these systems. Methods Using voxel‐based morphometry, gray and white matter volumes were compared in 15 medication‐free adolescents with generalized anxiety disorder (GAD; and no comorbid major depressive disorder) and 28 age‐ and sex‐matched healthy comparison subjects. Results Compared to healthy adolescents, youth with GAD had larger gray matter volumes in the right precuneus and right precentral gyrus and decreased gray matter volumes in the left orbital gyrus and posterior cingulate. White matter volumes were decreased in the left medial and superior frontal gyrus and were increased in the left inferior temporal gyrus in youth with GAD relative to healthy subjects. Conclusions Adolescents with GAD, who are early in the course of their illness, exhibit abnormalities in neural structures that subserve threat appraisal, modulation of fear responses, attachment, and mentalization.

  March 11, 2013   doi: 10.1002/da.22089   open full text
• Knowledge, Attitudes, And Practices Of Emergency Department Providers In The Care Of Suicidal Patients.
  Marian E. Betz, Ashley F. Sullivan, Anne P. Manton, Janice A. Espinola, Ivan Miller, Carlos A. Camargo, Edwin D. Boudreaux,.
  Depression and Anxiety. February 20, 2013
  Background We sought to examine the knowledge, attitudes, and practices of emergency department (ED) providers concerning suicidal patient care and to identify characteristics associated with screening for suicidal ideation (SI). Methods Six hundred thirty‐one providers at eight EDs completed a voluntary, anonymous survey (79% response rate). Results The median participant age was 35 (interquartile range: 30–44) years and 57% of the participants were females. Half (48%) were nurses and half were attending (22%) or resident (30%) physicians. More expressed confidence in SI screening skills (81–91%) than in skills to assess risk severity (64–70%), counsel patients (46–56%), or create safety plans (23–40%), with some differences between providers. Few thought mental health provider staffing was almost always sufficient (6–20%) or that suicidal patient treatment was almost always a top ED priority (15‐21%). More nurses (37%, 95% confidence interval [CI] 31–42%) than physicians (7%, 95% CI 4–10%) reported screening most or all patients for SI; this difference persisted after multivariable adjustment. In multivariable analysis, other factors associated with screening most or all patients for SI were self‐confidence in skills, (odds ratio [OR] 1.60, 95% CI 1.17–2.18), feeling that suicidal patient care was a top ED priority (OR 1.73, 95% CI 1.11–2.69) and 5+ postgraduate years of clinical experience (OR 2.06, 95% CI 1.03–4.13). Conclusions ED providers reported confidence in suicide screening skills but gaps in further assessment, counseling, or referral skills. Efforts to promote better identification of suicidal patients should be accompanied by a commensurate effort to improve risk assessment and management skills, along with improved access to mental health specialists.

  February 20, 2013   doi: 10.1002/da.22071   open full text
• The Association Between Anxiety Disorders And Suicidal Behaviors: A Systematic Review And Meta‐Analysis.
  Amrit Kanwar, Shaista Malik, Larry J. Prokop, Leslie A. Sim, David Feldstein, Zhen Wang, M. Hassan Murad.
  Depression and Anxiety. February 13, 2013
  Background Although anxiety has been proposed to be a potentially modifiable risk factor for suicide, research examining the relationship between anxiety and suicidal behaviors has demonstrated mixed results. Therefore, we aimed at testing the hypothesis that anxiety disorders are associated with suicidal behaviors and evaluate the magnitude and quality of supporting evidence. Methods A systematic literature search of multiple databases was conducted from database inception through August 2011. Two investigators independently reviewed and determined the eligibility and quality of the studies based upon a priori established inclusion criteria. The outcomes of interest were suicidal ideations, suicide attempts, completed suicides, and a composite outcome of any suicidal behaviors. We pooled odds ratios from the included studies using random effects models. Results Forty‐two observational studies were included. The studies had variable methodological quality due to inconsistent adjustment of confounders. Compared to those without anxiety, patients with anxiety were more likely to have suicidal ideations (OR = 2.89, 95% CI: 2.09, 4.00), attempted suicides (OR = 2.47, 95% CI: 1.96, 3.10), completed suicides (OR = 3.34, 95% CI: 2.13, 5.25), or have any suicidal behaviors (OR = 2.85, 95% CI: 2.35, 3.46). The increase in the risk of suicide was demonstrated for each subtype of anxiety except obsessive‐compulsive disorder (OCD). The quality of this evidence is considered low to moderate due to heterogeneity and methodological limitations. Conclusions This systematic review and meta‐analysis provides evidence that the rates of suicides are higher in patients with any type of anxiety disorders excluding OCD.

  February 13, 2013   doi: 10.1002/da.22074   open full text
• Complicated Grief And Bereavement In Young Adults Following Close Friend And Sibling Loss.
  Holly B. Herberman Mash, Carol S. Fullerton, Robert J. Ursano.
  Depression and Anxiety. February 11, 2013
  Background This study examined the association between types of loss (i.e., sibling or close friend) and relationship quality (i.e., depth and conflict) with complicated grief, depression, somatic symptoms, and world assumptions in bereaved young adults. Methods Participants were 107 young adults aged 17–29 years who were either bereaved or had never experienced a loss. Among bereaved participants, 66 lost a close friend and seven lost a sibling within the past 3 years (M = 1.63 years). Results Nineteen percent of the young adults met criteria for complicated grief and 31% had mild to severe depression. Participants with a deceased sibling reported greater depth in the relationship as compared to those who lost a friend. They were also more likely to have complicated grief (57% versus 15%) and report significantly higher levels of grief, depression, and somatic symptoms. Those who lost a sibling reported a lower sense of meaningfulness and benevolence of the world and self‐worth as compared with those who lost a close friend or had not experienced a loss. Conclusions Complicated grief and depression are common among bereaved young adults. Sibling loss is particularly distressing to young adults, due in part to the high level of relationship depth, and is associated with increased psychological and physical symptoms postloss.

  February 11, 2013   doi: 10.1002/da.22068   open full text
• Cognitive Behavior Therapy For Comorbid Obsessive‐Compulsive Disorder In High‐Functioning Autism Spectrum Disorders: A Randomized Controlled Trial.
  Ailsa J. Russell, Amita Jassi, Miguel A. Fullana, Hilary Mack, Kate Johnston, Isobel Heyman, Declan G. Murphy, David Mataix‐Cols.
  Depression and Anxiety. February 06, 2013
  Background High rates of anxiety disorders, particularly obsessive compulsive disorder (OCD) are reported in people with Autism spectrum disorders (ASD). Group cognitive behavioral treatment (CBT) has been found effective for anxiety in young people with ASD but not been OCD specific. One uncontrolled pilot study of individual CBT for OCD for adults with ASD showed good treatment efficacy. Methods Forty‐six adolescents and adults (mean age 26.9 years, 35 Males) with ASD and comorbid OCD were randomized to CBT for OCD or anxiety management (AM), a plausible control treatment. Treatments were matched in duration (mean of 17.4 sessions CBT; 14.4 sessions AM), the Yale–Brown Obsessive Compulsive Severity Scale (YBOCS) as primary outcome measure and evaluations blind to treatment group. Treatment response was defined as > 25% reduction in YBOCS total severity scores. Results Both treatments produced a significant reduction in OCD symptoms, within‐group effect sizes of 1.01 CBT group and 0.6 for the AM group. There were no statistically significant differences between the two groups at end of treatment, although more responders in the CBT group (45 versus 20%). Effect sizes for self‐rated improvement were small (0.33 CBT group; –0.05 AM group). Mild symptom severity was associated with improvement in the AM but not the CBT group. Family/carer factors were important for both groups, in that increased family accommodation was associated with poorer outcome. Conclusions Evidence‐based psychological interventions, both AM and CBT, were effective in treating comorbid OCD in young people and adults with ASD.

  February 06, 2013   doi: 10.1002/da.22053   open full text
• Benefits Of Child‐Focused Anxiety Treatments For Parents And Family Functioning.
  Courtney P. Keeton, Golda S. Ginsburg, Kelly L. Drake, Dara Sakolsky, Philip C. Kendall, Boris Birmaher, Anne Marie Albano, John S. March, Moira Rynn, John Piacentini, John T. Walkup.
  Depression and Anxiety. February 06, 2013
  Background To examine (1) changes in parent (global psychological distress, trait anxiety) and family (dysfunction, burden) functioning following 12 weeks of child‐focused anxiety treatment, and (2) whether changes in these parent and family factors were associated with child's treatment condition and response. Methods Participants were 488 youth ages 7–17 years (50% female; mean age 10.7 years) who met DSM‐IV‐TR criteria for social phobia, separation anxiety, and/or generalized anxiety disorder, and their parents. Youth were randomly assigned to 12 weeks of “Coping Cat” individual cognitive‐behavioral therapy (CBT), medication management with sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) within the multisite Child/Adolescent Anxiety Multimodal Study (CAMS). At pre‐ and posttreatment, parents completed measures of trait anxiety, psychological distress, family functioning, and burden of child illness; children completed a measure of family functioning. Blinded independent evaluators rated child's response to treatment using the Clinical Global Impression‐Improvement Scale at posttreatment. Results Analyses of covariance revealed that parental psychological distress and trait anxiety, and parent‐reported family dysfunction improved only for parents of children who were rated as treatment responders, and these changes were unrelated to treatment condition. Family burden and child‐reported family dysfunction improved significantly from pre‐ to posttreatment regardless of treatment condition or response. Conclusions Findings suggest that child‐focused anxiety treatments, regardless of intervention condition, can result in improvements in nontargeted parent symptoms and family functioning particularly when children respond successfully to the treatment.

  February 06, 2013   doi: 10.1002/da.22055   open full text
• Is Adolescent Generalized Anxiety Disorder A Magnet For Negative Parental Interpersonal Behaviors?
  William W. Hale, Theo A. Klimstra, Susan J. T. Branje, Saskia A. M. Wijsbroek, Wim H. J. Meeus.
  Depression and Anxiety. February 06, 2013
  Background Previous studies have found that perceived parental interpersonal interaction behaviors, such as rejection, overcontrol, and negative attachment behaviors, increase adolescent generalized anxiety disorder (GAD) symptoms. However, most of these studies have been cross‐sectional, as opposed to longitudinal, and have examined these perceived parental interaction behaviors individually. Hence, the goal of this longitudinal study is to examine these perceived parental behaviors and adolescent GAD symptoms together, in one model, to examine the unique effects each has on one another. Methods Participants were 923 adolescents from the general community. The adolescent population was comprised of both boys (50.7%) and girls (49.3%) with an average age of 12 at the first measurement. In a prospective, 5‐year longitudinal design, the adolescents completed questionnaires of parental interaction behaviors and adolescent GAD symptoms on the first, third, and fifth years of the study. Results Structural equation modeling cross‐lagged panel model analyses were conducted to examine the effects perceived parental interaction behaviors and adolescent GAD have on one another. It was found that adolescent GAD consistently predicted parental interpersonal interaction behaviors longitudinally. Conclusions It is suggested that adolescent GAD influences the perception of parental interpersonal behaviors. And the influence adolescent GAD may have on these perceived parental interpersonal behaviors is to create an environment in which the parents are perceived to begin to disengage in their interactions with their adolescent.

  February 06, 2013   doi: 10.1002/da.22065   open full text
• Fear Of Dying In Panic Attacks Predicts Suicide Attempt In Comorbid Depressive Illness: Prospective Evidence From The National Epidemiological Survey On Alcohol And Related Conditions.
  Zimri S. Yaseen, Hayley Chartrand, Ramin Mojtabai, James Bolton, Igor I. Galynker.
  Depression and Anxiety. December 20, 2012
  Context As a group, comorbid anxiety disorders among depressed persons have consistently been found to increase risk of suicide attempt (SA). Growing evidence supports the link between panic attacks (PAs) and suicidality, but prospective evidence is limited and the nature of the linkage remains unclear. The positive‐feedback model of suicide suggests that PAs eliciting catastrophic cognitions may drive SA. Objective To prospectively examine the relationship between PAs, panic symptoms and suicidality in individuals meeting DSM‐IV criteria for past‐year major depressive episodes in a large epidemiological study. Methods In data on 2,864 participants of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) wave 1 and 2 surveys with depressive disorders, the associations of PAs and panic symptoms with subsequent suicidal ideation (SI) and SAs were assessed using logistic regression. Results Past‐year PAs in wave 1 significantly increased odds for subsequent SI and attempt in the 3‐year follow‐up interval; however, in multivariate analyses, PAs were not a significant predictor, but PAs featuring fear of dying were. Further, among subjects with PAs, fear of dying during a PA increased the odds of subsequent SA sevenfold, even after controlling for comorbid disorders, demographic factors, and other PA symptoms. Conclusion PAs characterized by prominent morbid catastrophic cognitions may mediate the transition to SIs and SAs in subjects with depressive episodes. Presence of these symptoms in clinical settings may serve as a warning sign for future suicidality.

  December 20, 2012   doi: 10.1002/da.22039   open full text
• Clinical Predictors Of Long‐Term Outcome In Obsessive‐Compulsive Disorder.
  Ewgeni Jakubovski, Juliana B. Diniz, Carolina Valerio, Victor Fossaluza, Cristina Belotto‐Silva, Clarice Gorenstein, Eurípedes Miguel, Roseli G. Shavitt.
  Depression and Anxiety. October 25, 2012
  Background The purpose of this study was to investigate demographic and clinical factors associated with the long‐term outcome of obsessive‐compulsive disorder (OCD). Methods A hundred ninety‐six previously untreated patients with DSM‐IV criteria OCD completed a 12‐week randomized open trial of group cognitive‐behavioral therapy (GCBT) or fluoxetine, followed by 21 months of individualized, uncontrolled treatment, according to international guidelines for OCD treatment. OCD severity was assessed using the Yale–Brown Obsessive‐Compulsive Scale (Y‐BOCS) at different times over the follow‐up period. Demographics and several clinical variables were assessed at baseline. Results Fifty percent of subjects improved at least 35% from baseline, and 21.3% responded fully (final Y‐BOCS score < or = 8). Worse prognosis was associated with earlier age at onset of OCD (P = 0.045), longer duration of illness (P = 0.001) presence of at least one comorbid psychiatric disorder (P = 0.001), comorbidity with a mood disorder (P = 0.002), higher baseline Beck‐Depression scores (P = 0.011), positive family history of tics (P = 0.008), and positive family history of anxiety disorders (P = 0.008). Type of initial treatment was not associated with long‐term outcome. After correction for multiple testing, the presence of at least one comorbid disorder, the presence of a depressive disorder, and duration of OCD remained significant. Conclusions Patients under cognitive‐behavioral or pharmacological treatment improved continuously in the long run, regardless of initial treatment modality or degree of early response, suggesting that OCD patients benefit from continuous treatment. Psychiatric comorbidity, especially depressive disorders, may impair the long‐term outcome of OCD patients.

  October 25, 2012   doi: 10.1002/da.22013   open full text