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Autism Research

Impact factor: 3.988 5-Year impact factor: 4.776 Print ISSN: 1939-3792 Online ISSN: 1939-3806 Publisher: Wiley Blackwell (John Wiley & Sons)

Subject: Developmental Psychology

Most recent papers:

  • Sensorimotor learning and associated visual perception are intact but unrelated in autism spectrum disorder.
    Spencer J. Hayes, Matthew Andrew, Nathan C. Foster, Digby Elliott, Emma Gowen, Simon J. Bennett.
    Autism Research. October 20, 2017
    Humans show an astonishing capability to learn sensorimotor behaviours. However, data from sensorimotor learning experiments suggest the integration of efferent sensorimotor commands, afferent sensorimotor information, and visual consequences of a performed action during learning is different in autism, leading to atypical representation of internal action models. Here, we investigated the generalization of a sensorimotor internal action model formed during sensorimotor learning to a different, but associated, visual perception task. Although motor timing was generally less accurate in adults with autism, following practice with feedback both autistic adults, and controls, significantly improved performance of the movement sequence timing task by reducing timing error. In a subsequent perception task, both groups demonstrated similar temporal‐discrimination accuracy (autism = 75%; control = 76%). Significant correlations between motor timing error, and temporal‐discrimination during a perception task, was found for controls. No significant correlations were found for autistic adults. Our findings indicate that autistic adults demonstrated adaptation by reducing motor timing error through sensorimotor learning. However, the finding of significant correlations between motor timing error and temporal‐discrimination accuracy in the control group only suggests sensorimotor processes underpinning internal action model formation operate differently in autism. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We showed autistic adults learned a new motor skill, and visually judged moving objects, to a similar level of accuracy as a control group. Unlike the control group, there was no relationship between how well autistic adults learned the motor skill, and how well they judged objects. The lack of a relationship might be one of the reasons autistic adults interact differently in the social world.
    October 20, 2017   doi: 10.1002/aur.1882   open full text
  • Shank3‐Deficient rats exhibit degraded cortical responses to sound.
    Crystal T. Engineer, Kimiya C. Rahebi, Michael S. Borland, Elizabeth P. Buell, Kwok W. Im, Linda G. Wilson, Pryanka Sharma, Sven Vanneste, Hala Harony‐Nicolas, Joseph D. Buxbaum, Michael P. Kilgard.
    Autism Research. October 20, 2017
    Individuals with SHANK3 mutations have severely impaired receptive and expressive language abilities. While brain responses are known to be abnormal in these individuals, the auditory cortex response to sound has remained largely understudied. In this study, we document the auditory cortex response to speech and non‐speech sounds in the novel Shank3‐deficient rat model. We predicted that the auditory cortex response to sounds would be impaired in Shank3‐deficient rats. We found that auditory cortex responses were weaker in Shank3 heterozygous rats compared to wild‐type rats. Additionally, Shank3 heterozygous responses had less spontaneous auditory cortex firing and were unable to respond well to rapid trains of noise bursts. The rat model of the auditory impairments in SHANK3 mutation could be used to test potential rehabilitation or drug therapies to improve the communication impairments observed in individuals with Phelan‐McDermid syndrome. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Individuals with SHANK3 mutations have severely impaired language abilities, yet the auditory cortex response to sound has remained largely understudied. In this study, we found that auditory cortex responses were weaker and were unable to respond well to rapid sounds in Shank3‐deficient rats compared to control rats. The rat model of the auditory impairments in SHANK3 mutation could be used to test potential rehabilitation or drug therapies to improve the communication impairments observed in individuals with Phelan‐McDermid syndrome.
    October 20, 2017   doi: 10.1002/aur.1883   open full text
  • Neurexin gene family variants as risk factors for autism spectrum disorder.
    Jia Wang, Jianhua Gong, Li Li, Yanlin Chen, Lingfei Liu, HuaiTing Gu, Xiu Luo, Fang Hou, Jiajia Zhang, Ranran Song.
    Autism Research. October 16, 2017
    Increasing evidence suggests that abnormal synaptic function leads to neuronal developmental disorders and is an important component of the etiology of autism spectrum disorder (ASD). Neurexins are presynaptic cell‐adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals. Thus, neurexins are attractive candidate genes for autism. Since gene families have greater power to reveal genetic association than single genes, we designed this case‐control study to investigate six genetic variants in three neurexin genes (NRXN1, NRXN2, and NRXN3) in a Chinese population including 529 ASD patients and 1,923 healthy controls. We found that two SNPs were significantly associated with ASD after false discovery rate (FDR) adjustment for multiple comparisons. The NRXN2 rs12273892 polymorphism T allele and AT genotype were significantly associated with increased risk of ASD (respectively: OR = 1.328, 95% CI = 1.133–1.557, P < 0.001; OR = 1.528; 95% CI = 1.249–1.868, P < 0.001). The dominant model showed the same association (OR = 1.495, 95% CI = 1.231–1.816, P < 0.001). The NRXN3 rs12879016 polymorphism played a significant role in ASD susceptibility under the dominant model (OR = 0.747, 95% CI= 0.615–0.908, P = 0.023), with the same trend detected for the G allele and GT genotype (respectively: OR = 0.811, 95% CI = 0.699–0.941, P = 0.036; OR = 0.755, 95% CI = 0.615–0.928, P = 0.035). In conclusion, this study supports the importance of two genetic variants in the neurexin gene family in ASD susceptibility in China. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is highly heritable, and studies have found a number of candidate genes that might contribute to ASD. Neurexins are presynaptic cell‐adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals, and they play an important role in normal brain development and become candidate genes for autism. The purpose of our study is to explore the association between variants of the neurexins gene family and ASD in a Chinese population through a case‐control study.
    October 16, 2017   doi: 10.1002/aur.1881   open full text
  • Disrupted integration of exteroceptive and interoceptive signaling in autism spectrum disorder.
    Jean‐Paul Noel, Marisa Lytle, Carissa Cascio, Mark T. Wallace.
    Autism Research. October 14, 2017
    In addition to deficits in social communication, individuals diagnosed with Autism Spectrum Disorder (ASD) frequently exhibit changes in sensory and multisensory function. Recent evidence has focused on changes in audiovisual temporal processing, and has sought to relate these sensory‐based changes to weaknesses in social communication. These changes in audiovisual temporal function manifest as differences in the temporal epoch or “window” within which paired auditory and visual stimuli are integrated or bound, with those with ASD exhibiting expanded audiovisual temporal binding windows (TBWs). However, it is unknown whether this impairment is unique to audiovisual pairings, perhaps because of their relevance for speech processing, or whether it generalizes across pairings in different sensory modalities. In addition to the exteroceptive senses, there has been growing interest in ASD research in interoception (e.g., the monitoring of respiration, heartbeat, hunger, etc.), as these internally directed sensory processes appear to be altered as well in autism. In the current study, we sought to examine both exteroception and interoception in individuals with ASD and a group of typically developing (TD) matched controls, with an emphasis on temporal perception of audiovisual (exteroceptive) and cardiovisual (interoceptive to exteroceptive) cues. Results replicate prior findings showing expanded audiovisual TBWs in ASD in comparison to TD. In addition, strikingly, cardiovisual TBWs were fourfold larger in ASD than in TD, suggesting a putative complete lack of cardiovisual temporal acuity in ASD individuals. Results are discussed in light of recent evidence indicating a reduced tendency to rely on sensory priors in ASD. Autism Res 2017, 0: 000–000. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Studies have shown that individuals with autism have difficulty in separating auditory and visual events in time. People with autism also weight sensory evidence originating from the external world and from their body differently. We measured simultaneity judgments regarding visual and auditory events and between visual and heartbeat events. Results suggest that while individuals with autism show unusual temporal function across the senses in a general manner, this deficit is greater when pairings bridged between the external world and the internal body.
    October 14, 2017   doi: 10.1002/aur.1880   open full text
  • Comparing the effects of age, pubertal development, and symptom profile on cortisol rhythm in children and adolescents with autism spectrum disorder.
    Rachael A. Muscatello, Blythe A. Corbett.
    Autism Research. October 14, 2017
    Previous studies in children with autism spectrum disorder (ASD) have shown elevated evening cortisol; however, few studies have examined diurnal rhythm in adolescents with ASD. Adolescence is a time of significant physical and psychological change, and dysregulation of the hypothalamic–pituitary–adrenal axis may put adolescents with ASD at increased risk for internalizing disorders, such as anxiety and depression. The extent to which cortisol levels are associated with age, puberty and symptom profile was examined in 113 youth (ages 7–17) with ASD and typical development. Salivary samples were collected over 3 days in the home, 4 times per day (waking, 30‐min post‐waking, afternoon, evening). Results showed youth with ASD had higher evening cortisol and a blunted diurnal slope relative to TD youth. Pubertal development and age were significant predictors of evening cortisol, and adolescents with ASD had higher evening cortisol levels compared to children with ASD. The study extends previous reports of elevated evening cortisol in children with ASD to reveal high levels in adolescence as well. Adolescents with ASD also show a significantly blunted diurnal slope, which may be associated with risk of internalizing symptoms. Findings suggest elevated evening cortisol persists across development in youth with ASD, thus emphasizing a need to identify potential negative effects of excess cortisol exposure on health in ASD individuals. Lay Summary Elevations in stress hormone, cortisol, during the evening may indicate increased stress from changes throughout the day in youth with autism spectrum disorder (ASD). The current study shows that age and pubertal development are also related to increases in evening cortisol, and this maladaptive elevation in cortisol in ASD is not going away with age. These cortisol elevations may also be associated with other psychological symptoms and warrant further investigation in adolescents with ASD. Autism Res 2017, 0: 000–000. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    October 14, 2017   doi: 10.1002/aur.1879   open full text
  • Genetic background effects in Neuroligin‐3 mutant mice: Minimal behavioral abnormalities on C57 background.
    Thomas C. Jaramillo, Christine Ochoa Escamilla, Shunan Liu, Lauren Peca, Shari G. Birnbaum, Craig M. Powell.
    Autism Research. October 13, 2017
    Neuroligin‐3 (NLGN3) is a postsynaptic cell adhesion protein that interacts with presynaptic ligands including neurexin‐1 (NRXN1) [Ichtchenko et al., Journal of Biological Chemistry, 271, 2676–2682, 1996]. Mice harboring a mutation in the NLGN3 gene (NL3R451C) mimicking a mutation found in two brothers with autism spectrum disorder (ASD) were previously generated and behaviorally phenotyped for autism‐related behaviors. In these NL3R451C mice generated and tested on a hybrid C57BL6J/129S2/SvPasCrl background, we observed enhanced spatial memory and reduced social interaction [Tabuchi et al., Science, 318, 71–76, 2007]. Curiously, an independently generated second line of mice harboring the same mutation on a C57BL6J background exhibited minimal aberrant behavior, thereby providing apparently discrepant results. To investigate the origin of the discrepancy, we previously replicated the original findings of Tabuchi et al. by studying the same NL3R451C mutation on a pure 129S2/SvPasCrl genetic background. Here we complete the behavioral characterization of the NL3R451C mutation on a pure C57BL6J genetic background to determine if background genetics play a role in the discrepant behavioral outcomes involving NL3R451C mice. NL3R451C mutant mice on a pure C57BL6J background did not display spatial memory enhancements or social interaction deficits. We only observed a decreased startle response and mildly increased locomotor activity in these mice suggesting that background genetics influences behavioral outcomes involving the NL3R451C mutation. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Behavioral symptoms of autism can be highly variable, even in cases that involve identical genetic mutations. Previous studies in mice with a mutation of the Neuroligin‐3 gene showed enhanced learning and social deficits. We replicated these findings on the same and different genetic backgrounds. In this study, however, the same mutation in mice on a different genetic background did not reproduce our previous findings. Our results suggest that genetic background influences behavioral symptoms of this autism‐associated mutation.
    October 13, 2017   doi: 10.1002/aur.1857   open full text
  • Psychiatric comorbidities and use of psychotropic medications in people with autism spectrum disorder in the United States.
    Richard Houghton, Rose C. Ong, Federico Bolognani.
    Autism Research. September 30, 2017
    This study investigated psychotropic medication usage in two large, cohorts of people with autism spectrum disorder (ASD) throughout the calendar year 2014. The cohorts referred to individuals with commercial (employer‐sponsored) and Medicaid insurance in the United States. We aimed to understand prescribing patterns of such medications across a wide age‐range and in the presence/absence of other clinical and non‐clinical characteristics, including psychiatric comorbidities. We described the prevalence and length of prescriptions by age, psychiatric comorbidity and overall. We also fitted multivariable logistic regression models to describe the relationship between treatments and subject characteristics simultaneously. Eighty percent of the identified population was male, although gender did not impact the odds of receiving medication. Medication use was strongly associated with age, increasing most rapidly before adulthood; generally plateauing thereafter. All psychiatric comorbidities studied also individually increased the chances of medication use, with epilepsy and ADHD having the highest associations in both the commercial (OR > 7) and Medicaid (OR around 12) cohorts. Those in non‐capitated insurance plans, in foster care and white individuals also had increased odds of prescriptions. Overall, slightly more Medicaid enrollees received any psychotropic treatment (commercial: 64%, Medicaid: 69%). Nonetheless in both cohorts, a large proportion of individuals received treatment even without a diagnosis of any other psychiatric comorbidity (commercial: 31%, Medicaid: 33%). In summary, this report sheds new light on the latest patterns of psychiatric comorbidity profile and psycho‐pharmacological treatment patterns in ASD Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary this study identified a large number of children and adults in the US with autism spectrum disorder (autism) from employer‐sponsored and government funded (Medicaid) health insurance data. Psychotropic medications were used by over two thirds of people, and four in ten people received two medications at the same time. The chances of receiving medication increased for individuals with other psychiatric conditions (e.g., ADHD), and also increased with age.
    September 30, 2017   doi: 10.1002/aur.1848   open full text
  • Everyday executive function predicts adaptive and internalizing behavior among children with and without autism spectrum disorder.
    Emily Gardiner, Grace Iarocci.
    Autism Research. September 27, 2017
    Individuals with autism spectrum disorder (ASD) demonstrate challenges with executive function (EF), adaptive behavior, and mental health, all of which place long‐term wellbeing at risk. In the current study we examined the relation between parent‐rated EF and adaptive functioning and internalizing symptoms (anxiety, depression), as we expected that identifying the specific EF domains most closely related to these indices of functioning would illuminate opportunities for targeted intervention. Participants included 59 children and adolescents with ASD (M = 10.1 years) and 67 who were typically developing (TD) (M = 9.4 years) matched on age, IQ, mental age, and maternal education. Caregivers completed the Behavior Rating Inventory of EF (BRIEF) and Behavior Assessment System for Children, Second Edition (BASC‐2). Parents rated children with ASD as demonstrating significantly more challenges across most of the examined BRIEF and BASC‐2 indices and scales, with the exception of organization of materials (BRIEF) and anxiety (BASC‐2). For both groups, metacognitive EF processes emerged as strongly associated with practical, conceptual, and social skills, though different BRIEF scales emerged as significant across the component subdomains. In terms of the relation with mental health, BRIEF index scores were unrelated to anxiety for both groups. Behavior regulation, however, was significantly associated with depression symptoms for children with and without ASD. The findings highlight the possibility that targeting particular EF domains among individuals with and without ASD may not only have direct benefit for behavior regulation and metacognitive abilities, but may also extend to other areas of life, including adaptive behavior and concomitant internalizing symptomatology. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We examined whether parents' ratings of their children's flexibility and ability to monitor their behavior predicted adaptive skills (e.g., ability to complete day‐to‐day personal tasks, communicate, and socialize) and symptoms of anxiety and depression among children with and without autism spectrum disorder. For both groups, children's abilities to manage and monitor their behavior were strongly related to adaptive skills. Children's flexibility and ability to inhibit inappropriate behavior and control their emotions was associated with depression symptoms for both groups.
    September 27, 2017   doi: 10.1002/aur.1877   open full text
  • The association between theory of mind, executive function, and the symptoms of autism spectrum disorder.
    Catherine R. G. Jones, Emily Simonoff, Gillian Baird, Andrew Pickles, Anita J. S. Marsden, Jenifer Tregay, Francesca Happé, Tony Charman.
    Autism Research. September 25, 2017
    It has been strongly argued that atypical cognitive processes in autism spectrum disorder (ASD) contribute to the expression of behavioural symptoms. Comprehensive investigation of these claims has been limited by small and unrepresentative sample sizes and the absence of wide‐ranging task batteries. The current study investigated the cognitive abilities of 100 adolescents with ASD (mean age = 15 years 6 months), using 10 tasks to measure the domains of theory of mind (ToM) and executive function (EF). We used structural equation modelling as a statistically robust way of exploring the associations between cognition and parent‐reported measures of social communication and restricted and repetitive behaviours (RRBs). We found that ToM ability was associated with both social communication symptoms and RRBs. EF was a correlate of ToM but had no direct association with parent‐reported symptom expression. Our data suggest that in adolescence ToM ability, but not EF, is directly related to autistic symptom expression. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The behaviours that are common to autism spectrum disorder (ASD) have been linked to differences in thinking ability. We assessed autistic adolescents and found that social communication difficulties and the presence of restricted and repetitive behaviours related to difficulties in understanding other peoples’ minds (theory of mind). In contrast, these behaviours were not associated with the general thinking abilities involved in planning and executing tasks (executive function).
    September 25, 2017   doi: 10.1002/aur.1873   open full text
  • Executive function and functional and structural brain differences in middle‐age adults with autism spectrum disorder.
    B. Blair Braden, Christopher J. Smith, Amiee Thompson, Tyler K. Glaspy, Emily Wood, Divya Vatsa, Angela E. Abbott, Samuel C. McGee, Leslie C. Baxter.
    Autism Research. September 21, 2017
    There is a rapidly growing group of aging adults with autism spectrum disorder (ASD) who may have unique needs, yet cognitive and brain function in older adults with ASD is understudied. We combined functional and structural neuroimaging and neuropsychological tests to examine differences between middle‐aged men with ASD and matched neurotypical (NT) men. Participants (ASD, n = 16; NT, n = 17) aged 40–64 years were well‐matched according to age, IQ (range: 83–131), and education (range: 9–20 years). Middle‐age adults with ASD made more errors on an executive function task (Wisconsin Card Sorting Test) but performed similarly to NT adults on tests of delayed verbal memory (Rey Auditory Verbal Learning Test) and local visual search (Embedded Figures Task). Independent component analysis of a functional MRI working memory task (n‐back) completed by most participants (ASD = 14, NT = 17) showed decreased engagement of a cortico‐striatal‐thalamic‐cortical neural network in older adults with ASD. Structurally, older adults with ASD had reduced bilateral hippocampal volumes, as measured by FreeSurfer. Findings expand our understanding of ASD as a lifelong condition with persistent cognitive and functional and structural brain differences evident at middle‐age. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We compared cognitive abilities and brain measures between 16 middle‐age men with high‐functioning autism spectrum disorder (ASD) and 17 typical middle‐age men to better understand how aging affects an older group of adults with ASD. Men with ASD made more errors on a test involving flexible thinking, had less activity in a flexible thinking brain network, and had smaller volume of a brain structure related to memory than typical men. We will follow these older adults over time to determine if aging changes are greater for individuals with ASD.
    September 21, 2017   doi: 10.1002/aur.1842   open full text
  • Adaptive behavior in autism: Minimal clinically important differences on the Vineland‐II.
    C. H. Chatham, K. I. Taylor, T. Charman, X. Liogier D'ardhuy, E. Eule, A. Fedele, A. Y. Hardan, E. Loth, L. Murtagh, M. del Valle Rubido, A. San Jose Caceres, J. Sevigny, L. Sikich, L. Snyder, J. E. Tillmann, P. E. Ventola, K. L. Walton‐Bowen, P. P. Wang, T. Willgoss, F. Bolognani.
    Autism Research. September 21, 2017
    Autism Spectrum Disorder (ASD) is associated with persistent impairments in adaptive abilities across multiple domains. These social, personal, and communicative impairments become increasingly pronounced with development, and are present regardless of IQ. The Vineland Adaptive Behavior Scales, Second Edition (Vineland‐II) is the most commonly used instrument for quantifying these impairments, but minimal clinically important differences (MCIDs) on Vineland‐II scores have not been rigorously established in ASD. We pooled data from several consortia/registries (EU‐AIMS LEAP study, ABIDE‐I, ABIDE‐II, INFOR, Simons Simplex Collection and Autism Treatment Network [ATN]) and clinical investigations and trials (Stanford, Yale, Roche) resulting in a data set of over 9,000 individuals with ASD. Two approaches were used to estimate MCIDs: distribution‐based methods and anchor‐based methods. Distribution‐based MCID [d‐MCID] estimates included the standard error of the measurement, as well as one‐fifth and one‐half of the covariate‐adjusted standard deviation (both cross‐sectionally and longitudinally). Anchor‐based MCID [a‐MCID] estimates include the slope of linear regression of clinician ratings of severity on the Vineland‐II score, the slope of linear regression of clinician ratings of longitudinal improvement category on Vineland‐II change, the Vineland‐II change score maximally differentiating clinical impressions of minimal versus no improvement, and equipercentile equating. Across strata, the Vineland‐II Adaptive Behavior Composite standardized score MCID estimates range from 2.01 to 3.2 for distribution‐based methods, and from 2.42 to 3.75 for sample‐size‐weighted anchor‐based methods. Lower Vineland‐II standardized score MCID estimates were observed for younger and more cognitively impaired populations. These MCID estimates enable users of Vineland‐II to assess both the statistical and clinical significance of any observed change. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The Vineland Adaptive Behavior Scales (2nd edition; Vineland‐II) is the most widely used scale for assessing day‐to‐day “adaptive” skills. Yet, it is unknown how much Vineland‐II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2–3.75 points on the Vineland‐II Composite score represent the “minimal clinically‐important difference.” These estimates will help evaluate the benefits of potential new treatments for ASD.
    September 21, 2017   doi: 10.1002/aur.1874   open full text
  • The Hospital Anxiety and Depression scale: Factor structure and psychometric properties in older adolescents and young adults with autism spectrum disorder.
    Mirko Uljarević, Amanda L. Richdale, Helen McConachie, Darren Hedley, Ru Ying Cai, Hannah Merrick, Jeremy R. Parr, Ann Le Couteur.
    Autism Research. September 18, 2017
    Despite the high frequency of anxiety and depression symptoms in individuals with Autism Spectrum Disorder (ASD) and a significant impact of these comorbidities on both individuals with ASD and their families, research on the validity of anxiety and depression measures in the ASD population is currently lacking. The aim of this study was to explore the psychometric properties of the Hospital Anxiety and Depression Scale [HADS; Zigmond & Snaith, ] in a sample of older adolescents and young adults with ASD. One hundred and fifty one participants (UK Transition longitudinal study: N = 106; 75 males, Mage = 16.04 years, SD = 1.28; Longitudinal Study of Australian Schools Leavers with ASD: N = 45, 30 males; Mage = 18.35 years, SD = 2.55) completed the HADS and a range of mental health and well‐being measures. Combination of the Principal Component Analysis and Parallel Analysis indicated two factors as an optimal solution in our sample, accounting for 43.77% of variance with factors being identical in terms of content with the structure found in the general population. Internal consistency was good for the HADS anxiety scale (HADS‐A; .82–.84) and acceptable for the HADS depression scale (HADS‐D; .60–.72). Convergent validity of both HADS‐A and HADS‐D scales was excellent and divergent validity was acceptable. Our study represents a significant contribution to the literature by providing an initial validation of the HADS in older adolescents and younger adults with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Research on the validity of measurement of anxiety and depression in ASD is currently lacking. The aim of this study was to explore the properties of the Hospital Anxiety and Depression Scale (HADS) in a sample of 151 young people with ASD. Participants completed HADS and a range of mental health and well‐being measures. Encouragingly, our findings suggest that HADS provides a reliable and valid assessment of anxiety and depression in ASD.
    September 18, 2017   doi: 10.1002/aur.1872   open full text
  • Altered task‐related modulation of long‐range connectivity in children with autism.
    Ajay S. Pillai, Danielle McAuliffe, Balaji M. Lakshmanan, Stewart H. Mostofsky, Nathan E. Crone, Joshua B. Ewen.
    Autism Research. September 12, 2017
    Functional connectivity differences between children with autism spectrum disorder (ASD) and typically developing children have been described in multiple datasets. However, few studies examine the task‐related changes in connectivity in disorder‐relevant behavioral paradigms. In this paper, we examined the task‐related changes in functional connectivity using EEG and a movement‐based paradigm that has behavioral relevance to ASD. Resting‐state studies motivated our hypothesis that children with ASD would show a decreased magnitude of functional connectivity during the performance of a motor‐control task. Contrary to our initial hypothesis, however, we observed that task‐related modulation of functional connectivity in children with ASD was in the direction opposite to that of TDs. The task‐related connectivity changes were correlated with clinical symptom scores. Our results suggest that children with ASD may have differences in cortical segregation/integration during the performance of a task, and that part of the differences in connectivity modulation may serve as a compensatory mechanism. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Decreased connectivity between brain regions is thought to cause the symptoms of autism. Because most of our knowledge comes from data in which children are at rest, we do not know how connectivity changes directly lead to autistic behaviors, such as impaired gestures. When typically developing children produced complex movements, connectivity decreased between brain regions. In children with autism, connectivity increased. It may be that behavior‐related changes in brain connectivity are more important than absolute differences in connectivity in autism.
    September 12, 2017   doi: 10.1002/aur.1858   open full text
  • Pivotal response treatment for preschoolers with autism spectrum disorder: Defining a predictor profile.
    Kristin‐Lee Fossum, Loriann Williams, Nancy Garon, Susan E. Bryson, Isabel M. Smith.
    Autism Research. August 31, 2017
    Behavioral characteristics of children with autism spectrum disorder (ASD) who respond positively to Pivotal Response Treatment (PRT) have been described previously, based on single‐subject design research. The present study examined several such characteristics, as well as positive affect, as predictors of expressive language (EL) gains in a representative sample of preschoolers with ASD (n = 57) enrolled in a PRT‐based community early intervention program. Children's cognitive ability, positive affect, and levels of appropriate toy contact measured at the start of intervention each contributed significantly to the prediction of EL outcomes. Together these variables accounted for 40% of the total outcome variance. In addition, a profile of increased EL ability, positive affect and appropriate toy contact, and decreased social avoidance and stereotyped and repetitive vocalizations was associated with greater gains during intervention. Results are discussed in relation to their implications for understanding both the variable treatment response documented in children with ASD and how to tailor treatment to optimize individual benefit. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The study examined behavior of 57 preschoolers who made the greatest and least gains from 1 year of a community Pivotal Response Treatment program. Using pre‐treatment videos, we saw that children who made the most progress showed more language, positive affect, and appropriate interactions with toys, also less avoidance of people and fewer repetitive vocalizations. Behavior profiles can be used to match treatment to individual children's needs.
    August 31, 2017   doi: 10.1002/aur.1859   open full text
  • Children with autism spectrum disorder who improve with fever: Insights from the Simons Simplex Collection.
    Rebecca Grzadzinski, Catherine Lord, Stephan J. Sanders, Donna Werling, Vanessa H. Bal.
    Autism Research. August 31, 2017
    Literature indicates that some children with ASD may show behavioral improvements during fever; however, little is known about the behavioral profiles of these children. This study aims to (a) investigate the subset of children who show parent‐reported behavioral improvements associated with fever and (b) compare the demographic, behavioral, and genetic characteristics of this subset of children to children whose parents report no change during fever. Parents of 2,152 children from the Simons Simplex Collection provided information about whether and in which areas their child improved during fever. Children were randomly assigned into discovery or replication samples. In discovery analyses, children who reportedly improved with fever (Improve Group) were compared to those who reportedly did not improve (No Improve Group) on demographics, medical history, ASD symptoms, adaptive skills, and presence of de novo ASD‐associated mutations. Significant and marginal results from discovery analyses were tested in the replication sample. Parent reports of 17% of children indicated improvements during fever across a range of domains. Discovery and replication analyses revealed that the Improve Group had significantly lower non‐verbal cognitive skills (NVIQ) and language levels and more repetitive behaviors. Groups did not differ on demographic variables, parent‐report of current ASD symptoms or the presence of de novo mutations. Understanding the profiles of children who improve during episodes of fever may provide insights into innovative treatments for ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary This study explored characteristics of children with ASD who are reported to improve during fever. Parents of 17% of children with ASD report improvements across a range of domains during fever including cognition, communication, repetitive behaviors, social interaction, and behavior. Children who are reported to improve during fever have significantly lower non‐verbal cognitive skills and language levels and more repetitive behaviors. Understanding the profiles of children who improve during episodes of fever may provide insights into new treatments for ASD.
    August 31, 2017   doi: 10.1002/aur.1856   open full text
  • Gastrointestinal symptoms in autism spectrum disorder: A review of the literature on ascertainment and prevalence.
    Calliope Holingue, Carol Newill, Li‐Ching Lee, Pankaj J. Pasricha, M. Daniele Fallin.
    Autism Research. August 30, 2017
    There is no standard approach to measuring GI symptoms in individuals with ASD, despite postulated interactions. The objectives of this study were to (a) describe the range of GI symptom ascertainment approaches in studies of ASD, (b) describe the range of prevalence estimates across studies, and (c) assess associations between ascertainment approach and prevalence estimates. Studies published from 1/1/1980 to 1/31/2017 were collected via PubMed. Eligibility included studies with at least ten individuals with ASD that measured GI symptoms or conditions. We excluded review and hypothesis papers. We extracted information on study design, GI symptom ascertainment method, demographics, and ASD diagnostic criteria. From a subset of studies, we extracted GI symptom estimates. Out of a possible 386 titles, 144 were included. The prevalence range for constipation was 4.3–45.5% (median 22%), for diarrhea was 2.3–75.6% (median 13.0%), and for any or more than one symptom was 4.2–96.8% (median 46.8%). GI symptoms differed significantly by age of individuals, primary goal of study, study design, study sample, and who reported symptoms (P < .05). Due to small sample size, we were not able to test for associations between every GI symptom and study characteristic of interest, or examine associations between GI symptoms and intellectual or verbal disability. Studies used a broad range of methods to ascertain GI symptoms in ASD. GI symptoms varied widely across these studies, with significant differences by study characteristics. Our findings highlight the need for a reliable, valid GI assessment tool to be used consistently across studies of ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We reviewed studies having to do with autism spectrum disorder and the gastrointestinal system, dating back to 1980. We found that the median prevalence of constipation was 22.2%, diarrhea 13.0%, and any symptom 46.8%. All symptoms had a wide range of estimates across studies. GI symptoms were associated with characteristics of the study, including who measured the GI symptoms. We call for the development of a reliable and valid GI questionnaire for studies of ASD.
    August 30, 2017   doi: 10.1002/aur.1854   open full text
  • Analysis and functional characterization of sequence variations in ligand binding domain of thyroid hormone receptors in autism spectrum disorder (ASD) patients.
    Mahesh Kumar Kalikiri, Madhu Poornima Mamidala, Ananth N. Rao, Vidya Rajesh.
    Autism Research. August 30, 2017
    Autism spectrum disorder (ASD) is a neuro developmental disorder, reported to be on a rise in the past two decades. Thyroid hormone‐T3 plays an important role in early embryonic and central nervous system development. T3 mediates its function by binding to thyroid hormone receptors, TRα and TRβ. Alterations in T3 levels and thyroid receptor mutations have been earlier implicated in neuropsychiatric disorders and have been linked to environmental toxins. Limited reports from earlier studies have shown the effectiveness of T3 treatment with promising results in children with ASD and that the thyroid hormone levels in these children was also normal. This necessitates the need to explore the genetic variations in the components of the thyroid hormone pathway in ASD children. To achieve this objective, we performed genetic analysis of ligand binding domain of THRA and THRB receptor genes in 30 ASD subjects and in age matched controls from India. Our study for the first time reports novel single nucleotide polymorphisms in the THRA and THRB receptor genes of ASD individuals. Autism Res 2017. ©2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Thyroid hormone (T3) and thyroid receptors (TRα and TRβ) are the major components of the thyroid hormone pathway. The link between thyroid pathway and neuronal development is proven in clinical medicine. Since the thyroid hormone levels in Autistic children are normal, variations in their receptors needs to be explored. To achieve this objective, changes in THRA and THRB receptor genes was studied in 30 ASD and normal children from India. The impact of some of these mutations on receptor function was also studied.
    August 30, 2017   doi: 10.1002/aur.1838   open full text
  • Toward the identification of adaptive functioning intervention targets for intellectually‐able, transition‐aged youth with autism: An examination of caregiver responses on the Vineland‐II.
    Nicole L. Matthews, Amanda Malligo, Christopher J. Smith.
    Autism Research. August 29, 2017
    Little is known about specific adaptive functioning impairments in intellectually‐able individuals with autism spectrum disorder. In adolescents (n = 22) and young adults (n = 22) matched on composite IQ scores, this study examined profiles of cognitive and adaptive functioning, and caregiver responses on individual Vineland‐II items. Adaptive functioning standard scores were significantly lower than IQ scores, and the adult group had significantly lower adaptive functioning standard scores than the adolescent group. Examination of caregiver responses to individual Vineland‐II items identified more than 100 potential intervention targets. Differences favoring the adult group were observed on only 16 items across all three adaptive functioning domains, suggesting that little skill development is occurring during the transition to adulthood. Future research will examine the relevance of identified intervention targets to optimal outcomes. Autism Res 2017,. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Adolescents and young adults with autism spectrum disorder (ASD) without intellectual disability demonstrated impaired adaptive functioning skills (i.e., age appropriate skills necessary for independent living). Development of adaptive functioning skills appears to slow with age among individuals without intellectual disability. Findings clarify the specific adaptive functioning skills that transition‐aged youth with ASD have difficulty completing independently and will inform the development of interventions to increase the likelihood of independent living in adulthood.
    August 29, 2017   doi: 10.1002/aur.1855   open full text
  • Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder.
    Kumari Anshu, Ajay Kumar Nair, U.D. Kumaresan, Bindu M. Kutty, Shoba Srinath, T. Rao Laxmi.
    Autism Research. August 29, 2017
    Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5‐choice serial reaction time task (5‐CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5‐CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre‐attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex‐specific characteristics. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. Our work validates the use of the VPA model in the quest for evaluating suitable therapeutic targets for improving attentional performance.
    August 29, 2017   doi: 10.1002/aur.1852   open full text
  • Characterization of early communicative behavior in mouse models of neurofibromatosis type 1.
    Susan E. Maloney, Krystal C. Chandler, Corina Anastasaki, Michael A. Rieger, David H. Gutmann, Joseph D. Dougherty.
    Autism Research. August 26, 2017
    Neurofibromatosis type 1 (NF1) is a monogenic neurodevelopmental disease caused by germline loss‐of‐function mutations in the NF1 tumor suppressor gene. Cognitive impairments are observed in approximately 80% of children with this disease, with 45–60% exhibiting autism spectrum disorder (ASD) symptomatology. In light of the high comorbidity rate between ASD and NF1, we assessed early communicative behavior by maternal‐separation induced pup ultrasonic vocalizations (USV) and developmental milestones in two distinct Nf1 genetically engineered models, one modeling clinical germline heterozygous loss of Nf1 function (Nf1+/– mice), and a second with somatic biallelic Nf1 inactivation in neuroglial progenitor cells (Nf1GFAPCKO mice). We observed altered USV production in both models: Nf1+/– mice exhibited both increased USVs across development and alterations in aspects of pitch, while Nf1GFAPCKO mice demonstrated a decrease in USVs. Developmental milestones, such as weight, pinnae detachment, and eye opening, were not disrupted in either model, indicating the USV deficits were not due to gross developmental delay, and likely reflected more specific alterations in USV circuitry. In this respect, increased whole‐brain serotonin was observed in Nf1+/– mice, but whole‐brain levels of dopamine and its metabolites were unchanged at the age of peak USV disruption, and USV alterations did not correlate with overall level of neurofibromin loss. The early communicative phenotypes reported herein should motivate further studies into the risks mediated by haploinsufficiency and biallelic deletion of Nf1 across a full battery of ASD‐relevant behavioral phenotypes, and a targeted analysis of underlying circuitry disruptions. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder caused by mutation of the NF1 gene, in which 80% of affected children exhibit cognitive and behavioral issues. Based on emerging evidence that NF1 may be an autism predisposition gene, we examined autism spectrum disorder (ASD)‐relevant early communicative behavior in Nf1 mouse models and observed alterations in both models. The changes in early communicative behavior in Nf1 mutant mice should motivate further studies into the causative factors and potential treatments for ASD arising in the context of NF1.
    August 26, 2017   doi: 10.1002/aur.1853   open full text
  • Processing of co‐reference in autism spectrum disorder.
    Philippa L. Howard, Simon P. Liversedge, Valerie Benson.
    Autism Research. August 22, 2017
    Accuracy for reading comprehension and inferencing tasks has previously been reported as reduced for individuals with autism spectrum disorder (ASD), relative to typically developing (TD) controls. In this study, we used an eye movements and reading paradigm to examine whether this difference in performance accuracy is underpinned by differences in the inferential work required to compute a co‐referential link. Participants read two sentences that contained a category noun (e.g., bird) that was preceded by and co‐referred to an exemplar that was either typical (e.g., pigeon) or atypical (e.g., penguin). Both TD and ASD participants showed an effect of typicality for gaze durations upon the category noun, with longer times being observed when the exemplar was atypical, in comparison to typical. No group differences or interactions were detected for target processing, and verbal language proficiency was found to predict general reading and inferential skill. The only difference between groups was that individuals with ASD engaged in more re‐reading than TD participants. These data suggest that readers with ASD do not differ in the efficiency with which they compute anaphoric links on‐line during reading. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Individuals with autism spectrum disorder (ASD) have previously been reported to have difficulties with reading comprehension. This study examined whether a difference in the speed with which individuals with ASD form connections between words (co‐reference processing) may contribute to comprehension difficulties. No evidence was found to suggest that ASD readers differ to typically developing readers in the speed of co‐reference processing. Therefore, this data would suggest that differences in co‐reference processing are unlikely to account for reading comprehension difficulties in ASD.
    August 22, 2017   doi: 10.1002/aur.1845   open full text
  • Reading comprehension of ambiguous sentences by school‐age children with autism spectrum disorder.
    Meghan M. Davidson, Susan Ellis Weismer.
    Autism Research. August 22, 2017
    Weak central coherence (processing details over gist), poor oral language abilities, poor suppression, semantic interference, and poor comprehension monitoring have all been implicated to affect reading comprehension in individuals with autism spectrum disorder (ASD). This study viewed the contributions of different supporting skills as a collective set of skills necessary for context integration—a multi‐component view—to examine individual differences in reading comprehension in school‐age children (8–14 years) with ASD (n = 23) and typically developing control peers (n = 23). Participants completed a written ambiguous sentence comprehension task in which participants had to integrate context to determine the correct homonym meaning via picture selection. Both comprehension products (i.e., offline representations after reading) and processes (i.e., online processing during reading) were evaluated. Results indicated that children with ASD, similar to their TD peers, integrated the context to access the correct homonym meanings while reading. However, after reading the sentences, when participants were asked to select the meanings, both groups experienced semantic interference between the two meanings. This semantic interference hindered the children with ASD's sentence representation to a greater degree than their peers. Individual differences in age/development, word recognition, vocabulary breadth (i.e., number of words in the lexicon), and vocabulary depth (i.e., knowledge of the homonym meanings) contributed to sentence comprehension in both children with ASD and their peers. Together, this evidence supports a multi‐component view, and that helping children with ASD develop vocabulary depth may have cascading effects on their reading comprehension. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Like their peers, children with ASD were able to integrate context, or link words while reading sentences with ambiguous words (words with two meanings). After reading the sentences, both groups found it hard to pick the correct meaning of the ambiguous sentence and this decision was more difficult for the participants with ASD. Older children, children with better word reading abilities, and children with higher vocabularies were better at understanding ambiguous sentences. Helping children with ASD to develop richer vocabularies could be important for improving their reading comprehension.
    August 22, 2017   doi: 10.1002/aur.1850   open full text
  • Production and perception of emotional prosody by adults with autism spectrum disorder.
    Daniel J. Hubbard, Daniel J. Faso, Peter F. Assmann, Noah J. Sasson.
    Autism Research. August 17, 2017
    This study examined production and perception of affective prosody by adults with autism spectrum disorder (ASD). Previous research has reported increased pitch variability in talkers with ASD compared to typically developing (TD) controls in grammatical speaking tasks (e.g., comparing interrogative vs. declarative sentences), but it is unclear whether this pattern extends to emotional speech. In this study, speech recordings in five emotion contexts (angry, happy, interested, sad, and neutral) were obtained from 15 adult males with ASD and 15 controls (Experiment 1), and were later presented to 52 listeners (22 with ASD) who were asked to identify the emotion expressed and rate the level of naturalness of the emotion in each recording (Experiment 2). Compared to the TD group, talkers with ASD produced phrases with greater intensity, longer durations, and increased pitch range for all emotions except neutral, suggesting that their greater pitch variability was specific to emotional contexts. When asked to identify emotion from speech, both groups of listeners were more accurate at identifying the emotion context from speech produced by ASD speakers compared to TD speakers, but rated ASD emotional speech as sounding less natural. Collectively, these results reveal differences in emotional speech production in talkers with ASD that provide an acoustic basis for reported perceptions of oddness in the speech presentation of adults with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary This study examined emotional speech communication produced and perceived by adults with autism spectrum disorder (ASD) and typically‐developing (TD) controls. Compared to the TD group, talkers with ASD produced emotional phrases that were louder, longer, and more variable in pitch. Both ASD and TD listeners were more accurate at identifying emotion in speech produced by ASD speakers compared to TD speakers, but rated ASD emotional speech as sounding less natural.
    August 17, 2017   doi: 10.1002/aur.1847   open full text
  • Sticking with it: Psychotherapy outcomes for adults with autism spectrum disorder in a university counseling center setting.
    Emily Anderberg, Jonathan C. Cox, E. Shannon Neeley Tass, David M. Erekson, Terisa P. Gabrielsen, Jared S. Warren, Jared Cline, Devin Petersen, Mikle South.
    Autism Research. August 17, 2017
    Young adults with autism spectrum disorders (ASD) experience high rates of comorbid mental health concerns in addition to distress arising from the core symptoms of autism. Many adults with ASD seek psychological treatment in outpatient facilities in their communities that are not specifically geared toward individuals with ASD. However, few studies have looked at the effectiveness of standard psychotherapeutic care in adults with ASD. This study aimed to discover how individuals with ASD fare in psychotherapy within a college counseling setting, compared to their neurotypical peers. Clients with ASD (n = 76) or possible ASD (n = 91) were retrospectively identified from counseling center case notes. Data from the Outcome Questionnaire‐45 (OQ) were retrieved for each therapy session as a measure of client distress. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers (n = 21,546), and improved about the same amount from pre‐ to post‐treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on OQ reports. Results are discussed with implications for university and other community based treatment settings. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary This study aimed to discover how individuals with autism spectrum disorders (ASD) fare in psychotherapy within a university counseling setting, compared to their neurotypical peers. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers, and improved about the same amount from pre‐ to post‐treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on Outcome Questionnaire‐45 reports.
    August 17, 2017   doi: 10.1002/aur.1843   open full text
  • Prenatal exposure to fever is associated with autism spectrum disorder in the boston birth cohort.
    Martha Brucato, Christine Ladd‐Acosta, Mengying Li, Deanna Caruso, Xiumei Hong, Jamie Kaczaniuk, Elizabeth A. Stuart, M. Daniele Fallin, Xiaobin Wang.
    Autism Research. August 11, 2017
    Autism spectrum disorder (ASD) is phenotypically and etiologically heterogeneous, with evidence for genetic and environmental contributions to disease risk. Research has focused on the prenatal period as a time where environmental exposures are likely to influence risk for ASD. Epidemiological studies have shown significant associations between prenatal exposure to maternal immune activation (MIA), caused by infections and fever, and ASD. However, due to differences in study design and exposure measurements no consistent patterns have emerged revealing specific times or type of MIA exposure that are most important to ASD risk. No prior studies have examined prenatal MIA exposure and ASD risk in an under‐represented minority population of African ancestry. To overcome these limitations, we estimated the association between prenatal exposure to fever and maternal infections and ASD in a prospective birth cohort of an understudied minority population in a city in the United States. No association was found between prenatal exposure to genitourinary infections or flu and the risk of ASD in a nested sample of 116 ASD cases and 988 typically developing controls in crude or adjusted analyses. Prenatal exposure to fever was associated with increased ASD risk (aOR 2.02 [1.04–3.92]) after adjustment for educational attainment, marital status, race, child sex, maternal age, birth year, gestational age, and maternal smoking. This effect may be specific to fever during the third trimester (aOR 2.70 [1.00–7.29]). Our findings provide a focus for future research efforts and ASD prevention strategies across diverse populations. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We looked at whether activation of the immune system during pregnancy increases the chance a child will develop ASD. We examined 116 children with ASD and 988 children without ASD that came from a predominantly low income, urban, minority population. We found that having the flu or genitourinary tract infections during pregnancy is not related to the child being diagnosed with ASD. However, we did find children were at increased risk for ASD when their mothers had a fever during pregnancy.
    August 11, 2017   doi: 10.1002/aur.1841   open full text
  • Early autism symptoms in infants with tuberous sclerosis complex.
    Nicole M. McDonald, Kandice J. Varcin, Rujuta Bhatt, Joyce Y. Wu, Mustafa Sahin, Charles A. Nelson, Shafali S. Jeste.
    Autism Research. August 11, 2017
    Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic syndrome that confers significantly increased risk for autism spectrum disorder (ASD), with 50–60% of infants with TSC meeting criteria for ASD by 3 years of age. In a previous study of the current longitudinal cohort, we found that infants with TSC who develop ASD (TSC/ASD) evidence decreased cognitive abilities that diverge from infants with TSC and no ASD (TSC/no ASD). We extended this work by asking whether TSC/ASD infants (n = 13) differed from TSC/no ASD infants (n = 10) and infants with low developmental risk and no ASD (LR; n = 21) in their social communication functioning during the first year of life. We measured early ASD symptoms with the Autism Observation Scale for Infants (AOSI) at 9 and 12 months of age. At both ages, infants in the TSC/ASD group had significantly higher AOSI total scores than infants in the TSC/no ASD and LR groups, which were not fully explained by differences in cognitive abilities. Several items on the AOSI at both ages were predictive of ASD outcome, particularly those representing core social communication deficits (e.g., social referencing). Our findings signal the need for further study of this population within the first year and provide strong justification for early identification and early intervention targeting social communication skills in infants with TSC. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary We examined early signs of autism spectrum disorder (ASD) in infants with tuberous sclerosis complex (TSC), approximately 50% of whom will meet criteria for ASD by age 3. Infants with TSC and ASD showed deficits in social communication behaviors by 9 months of age that were clearly distinguishable from behaviors in infants with TSC who do not develop ASD and low risk infants. Results support the importance of early ASD screening and intervention for infants with TSC.
    August 11, 2017   doi: 10.1002/aur.1846   open full text
  • Normative data and psychometric properties of a farsi translation of the strange stories test.
    Zahra Shahrivar, Mehdi Tehrani‐Doost, Anahita Khorrami Banaraki, Azar Mohammadzadeh, Francesca Happe.
    Autism Research. August 11, 2017
    Background and objective The Strange Stories test is one of the most commonly used tests to evaluate advanced “theory of mind,” i.e. attribution of mental states. Normative data and psychometric properties of a new Farsi translation of this test were evaluated in a large community‐based sample of Iranian school‐aged children. Methods: Through randomized cluster sampling, 398 children aged 9–11 years studying at 20 elementary schools were recruited from 4 central regions of Tehran, Iran. The mean age of the students was 9.96 years (SD = 0.92), and 51% were girls (n = 202). The Child Behavior Checklist (CBCL) was completed by parents. The Strange Stories test was completed by all children and repeated for 20% of them after 2–4 weeks to assess the test‐retest reliability. Findings: Students in upper grades had higher scores (P < .01); age predicted 2% of variance on the mental state score. Girls had significantly higher mentalizing scores than boys (P = .003). The split‐half internal reliability coefficient was good (0.73). The test‐retest reliability was fair to good. Item‐scale score correlations were all significant (P < .01). Conclusion: This new translation of the Strange Stories test is a reliable and valid instrument to evaluate higher level theory of mind abilities in community samples of Farsi speaking children. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary “Mentalizing” or “theory of mind,” the ability to recognize others' mental states, is a key aspect of social understanding. Mentalizing problems are characteristic of some clinical conditions such as autism. The Strange Stories is a test evaluating mentalizing in every day social situations. It was translated into Farsi language and administered to a group of Iranian school‐aged children. The instrument was useful in assessing children's mind reading. Older children and girls were better in mentalizing ability.
    August 11, 2017   doi: 10.1002/aur.1844   open full text
  • Social motivation and implicit theory of mind in children with autism spectrum disorder.
    Kimberly Burnside, Kristyn Wright, Diane Poulin‐Dubois.
    Autism Research. August 01, 2017
    According to the social motivation theory of autism, children who develop Autism Spectrum Disorder (ASD) have early deficits in social motivation, which is expressed by decreased attention to social information. These deficits are said to lead to impaired socio‐cognitive development, such as theory of mind (ToM). There is little research focused on the relation between social motivation and ToM in this population. The goal of the present study was to investigate the link between one aspect of social motivation, social orienting, and ToM in preschoolers with ASD. It was expected that, in contrast to typically developing (TD) children, children with ASD would show impaired performance on tasks measuring social orienting and ToM. It was also expected that children's performance on the social orienting tasks would be correlated with their performance on the ToM task. A total of 17 children with ASD and 16 TD children participated in this study. Participants completed two social orienting tasks, a face preference task and a biological motion preference task, as well an implicit false belief task. Results reveal that TD children, but not children with ASD, exhibited social preference as measured by a preference for faces and biological motion. Furthermore, children with ASD tended to perform worse on the ToM task compared to their TD counterparts. Performance on the social motivation tasks and the ToM task tended to be related but only for the TD children. These findings suggest that ToM is multifaceted and that motivational deficits might have downstream effects even on implicit ToM. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    August 01, 2017   doi: 10.1002/aur.1836   open full text
  • Shared atypical default mode and salience network functional connectivity between autism and schizophrenia.
    Heng Chen, Lucina Q. Uddin, Xujun Duan, Junjie Zheng, Zhiliang Long, Youxue Zhang, Xiaonan Guo, Yan Zhang, Jingping Zhao, Huafu Chen.
    Autism Research. July 21, 2017
    Schizophrenia and autism spectrum disorder (ASD) are two prevalent neurodevelopmental disorders sharing some similar genetic basis and clinical features. The extent to which they share common neural substrates remains unclear. Resting‐state fMRI data were collected from 35 drug‐naïve adolescent participants with first‐episode schizophrenia (15.6 ± 1.8 years old) and 31 healthy controls (15.4 ± 1.6 years old). Data from 22 participants with ASD (13.1 ± 3.1 years old) and 21 healthy controls (12.9 ± 2.9 years old) were downloaded from the Autism Brain Imaging Data Exchange. Resting‐state functional networks were constructed using predefined regions of interest. Multivariate pattern analysis combined with multi‐task regression feature selection methods were conducted in two datasets separately. Classification between individuals with disorders and controls was achieved with high accuracy (schizophrenia dataset: accuracy = 83%; ASD dataset: accuracy = 80%). Shared atypical brain connections contributing to classification were mostly present in the default mode network (DMN) and salience network (SN). These functional connections were further related to severity of social deficits in ASD (p = 0.002). Distinct atypical connections were also more related to the DMN and SN, but showed different atypical connectivity patterns between the two disorders. These results suggest some common neural mechanisms contributing to schizophrenia and ASD, and may aid in understanding the pathology of these two neurodevelopmental disorders. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    July 21, 2017   doi: 10.1002/aur.1834   open full text
  • Basal ganglia and autism – a translational perspective.
    Krishna Subramanian, Cheryl Brandenburg, Fernanda Orsati, Jean‐Jacques Soghomonian, John P. Hussman, Gene J. Blatt.
    Autism Research. July 21, 2017
    The basal ganglia are a collection of nuclei below the cortical surface that are involved in both motor and non‐motor functions, including higher order cognition, social interactions, speech, and repetitive behaviors. Motor development milestones that are delayed in autism such as gross motor, fine motor and walking can aid in early diagnosis of autism. Neuropathology and neuroimaging findings in autism cases revealed volumetric changes and altered cell density in select basal ganglia nuclei. Interestingly, in autism, both the basal ganglia and the cerebellum are impacted both in their motor and non‐motor domains and recently, found to be connected via the pons through a short disynaptic pathway. In typically developing individuals, the basal ganglia plays an important role in: eye movement, movement coordination, sensory modulation and processing, eye‐hand coordination, action chaining, and inhibition control. Genetic models have proved to be useful toward understanding cellular and molecular changes at the synaptic level in the basal ganglia that may in part contribute to these autism‐related behaviors. In autism, basal ganglia functions in motor skill acquisition and development are altered, thus disrupting the normal flow of feedback to the cortex. Taken together, there is an abundance of emerging evidence that the basal ganglia likely plays critical roles in maintaining an inhibitory balance between cortical and subcortical structures, critical for normal motor actions and cognitive functions. In autism, this inhibitory balance is disturbed thus impacting key pathways that affect normal cortical network activity. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Habit learning, action selection and performance are modulated by the basal ganglia, a collection of groups of neurons located below the cerebral cortex in the brain. In autism, there is emerging evidence that parts of the basal ganglia are structurally and functionally altered disrupting normal information flow. The basal ganglia through its interconnected circuits with the cerebral cortex and the cerebellum can potentially impact various motor and cognitive functions in the autism brain.
    July 21, 2017   doi: 10.1002/aur.1837   open full text
  • Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism.
    Jean‐Jacques Soghomonian, Kunzhong Zhang, Sujithra Reprakash, Gene J. Blatt.
    Autism Research. July 14, 2017
    Recent neuropathology studies in human brains indicate that several areas of the prefrontal cortex have decreased numbers of parvalbumin interneurons or decreased parvalbumin expression in Autism Spectrum disorders (ASD) [Hashemi, Ariza, Rogers, Noctor, & Martinez‐Cerdeno, 2017; Zikopoulos & Barbas, ]. These data suggest that a deficit in parvalbumin may be a key neuropathology of ASD and contribute to altered GABAergic inhibition. However, it is unclear if a deficit in parvalbumin is a phenomenon that occurs in regions other than the cerebral cortex. The cerebellum is a major region where neuropathology was first detected in ASD over three decades ago [Bauman & Kemper, ]. In view of the documented association between parvalbumin‐expressing neurons and autism, the objective of the present study was to determine if parvalbumin gene expression is also altered in Purkinje neurons of the cerebellum. Radioisotopic in situ hybridization histochemistry was used on human tissue sections from control and ASD brains in order to detect and measure parvalbumin mRNA levels at the single cell level in Purkinje cells of Crus II of the lateral cerebellar hemispheres. Results indicate that parvalbumin mRNA levels are significantly lower in Purkinje cells in ASD compared to control brains. This decrease was not influenced by post‐mortem interval or age at death. This result indicates that decreased parvalbumin expression is a more widespread feature of ASD. We discuss how this decrease may be implicated in altered cerebellar output to the cerebral cortex and in key ASD symptoms. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    July 14, 2017   doi: 10.1002/aur.1835   open full text
  • Developmental delays in emotion regulation strategies in preschoolers with autism.
    Heather J. Nuske, Darren Hedley, Alexandra Woollacott, Phoebe Thomson, Suzanne Macari, Cheryl Dissanayake.
    Autism Research. July 11, 2017
    Children with autism spectrum disorder (ASD) commonly present with difficulty regulating negative emotions, which has been found to impact their behavioral and mental health. Little research has documented the strategies that children with ASD use to regulate their emotion to understand whether they use qualitatively different strategies to children without ASD, whether these are developmentally delayed, or both. Forty‐four children with ASD and 29 typically‐developing children (2–4 years) were given tasks designed to mimic everyday life experiences requiring children to manage low‐level stress (e.g., waiting for a snack) and children's emotion regulation strategies were coded. Parents reported on their child's mental health, wellbeing, and self‐development. The results suggest differences in using emotion regulation strategies in children with ASD, reflecting a delay, rather than a deviance when compared to those used by children without ASD. Only children with ASD relied on their family members for physical and communicative soothing; the typically developing children relied on people outside of their family for help regulating their emotion. More frequent approach/less frequent avoidance was related to a higher self‐evaluation in both groups, but was only additionally related to higher self‐recognition and autonomy in the ASD group. These findings help to identify important emotion regulation intervention targets for this population, including supporting communication with people outside of the family and independence. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    July 11, 2017   doi: 10.1002/aur.1827   open full text
  • Socio‐sexual functioning in autism spectrum disorder: A systematic review and meta‐analyses of existing literature.
    Grace I. P. Hancock, Mark A. Stokes, Gary B. Mesibov.
    Autism Research. July 10, 2017
    Socio‐sexual functioning encompasses an individual's interests, behaviors, and knowledge with respect to sexual, romantic, and social aspects of life. An individual's understanding of these domains is developed through a range of informal and formal avenues of sexual health education. The current model demonstrated this and proposed that, compared to typically developing individuals, those with ASD develop socio‐sexual functioning differently due to having less peer engagement, less relationship experience, more parental guidance, greater use of online materials, receive less school‐based sexual health education, and more support from wellbeing services. Systematic review and meta‐analysis of existing literature revealed that individuals with ASD have greater difficultly adhering to privacy norms, engage in less social behavior, are described as engaging in less appropriate sexual behavior, have greater concerns about themselves, and receive less sexual health education. Having fewer opportunities for appropriate informal and formal sexual health education leaves them at a double disadvantage from others who are receiving this information from both of these avenues. Some of the current meta‐analytic results are cautioned by large l‐square statistics which suggest that a degree of variance is being caused by extraneous factors. Further empirical research in this area is needed to overcome current design and sample limitations. Finally, the Sexual Behavior Scale was the most commonly utilized tool in the meta‐analyzed studies, thus comprehensive evaluation of its functioning is warranted. The importance of work in this area is highlighted by the central role of social and sexual wellbeing on one's quality of life. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    July 10, 2017   doi: 10.1002/aur.1831   open full text
  • Are autistic traits associated with suicidality? A test of the interpersonal‐psychological theory of suicide in a non‐clinical young adult sample.
    M. K. Pelton, S. A. Cassidy.
    Autism Research. July 07, 2017
    Autism spectrum conditions (ASC) has recently been associated with increased risk of suicidality. However, no studies have explored how autistic traits may interact with current models of suicidal behavior in a non‐clinical population. The current study therefore explored how self‐reported autistic traits interact with perceived burdensomeness and thwarted belongingness in predicting suicidal behavior, in the context of the Interpersonal‐Psychological Theory of Suicide (IPTS). 163 young adults (aged 18–30 years) completed an online survey including measures of thwarted belonging and perceived burdensomeness (Interpersonal Needs Questionnaire), self‐reported autistic traits (Autism Spectrum Quotient), current depression (Centre for Epidemiological Studies Depression Scale), and lifetime suicidality (Suicide Behavior Questionnaire‐Revised). Results showed that burdensomeness and thwarted belonging significantly mediated the relationship between autistic traits and suicidal behavior. Both depression and autistic traits significantly predicted thwarted belonging and perceived burdensomeness. Autistic traits did not significantly moderate the relationship between suicidal behavior and thwarted belonging or perceived burdensomeness. Results suggest that the IPTS provides a useful framework for understanding the influence of autistic traits on suicidal behavior. However, the psychometric properties of these measures need be explored in those with clinically confirmed diagnosis of ASC. Autism Res. 2017. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.
    July 07, 2017   doi: 10.1002/aur.1828   open full text
  • Language and motor skills in siblings of children with autism spectrum disorder: A meta‐analytic review.
    Dunia Garrido, Dafina Petrova, Linda R. Watson, Rocio Garcia‐Retamero, Gloria Carballo.
    Autism Research. July 07, 2017
    Children with autism spectrum disorder (ASD) show significant linguistic and motor impairments compared to children with typical development (TD). Findings from studies of siblings of children with ASD show similarities to conclusions from studies of children with ASD. The current meta‐analysis reviewed studies reporting linguistic and/or motor skills in siblings of children with ASD compared to siblings of children with TD. Thirty‐four studies published between 1994 and 2016 met all inclusion criteria. We compared three different age groups (12 months or younger, 13 to 24 months, and 25 to 36 months). At 12 months, compared to siblings of children with TD, siblings of children with ASD had worse receptive language (d = −.43, 95% CI [−.53, −.33]) and expressive language skills (d = −.40, 95% CI [−.57, −.23]), and these effects were sustained at 24 and 36 months. Similar, albeit smaller differences in fine motor skills were detected at 12 months (d = −.22, 95% CI [−.39, −.04]), and these differences were larger at 36 months (d = −.36, 95% CI [−.54, −.17]). There were differences in gross motor skills at 12 months (d = −.22, 95% CI [−.40, −.04]), but only a few studies were available at later ages. Compared to siblings of children with TD, infants who have siblings with ASD have worse linguistic and motor skills. These differences are detectable as early as when infants are 12 months old and seem to be sustained until they are 3 years old. Differences in language skills are larger than those in motor skills, especially during the first year. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    July 07, 2017   doi: 10.1002/aur.1829   open full text
  • Prenatal maternal stress events and phenotypic outcomes in Autism Spectrum Disorder.
    Kandice J. Varcin, Gail A. Alvares, Mirko Uljarević, Andrew J. O. Whitehouse.
    Autism Research. July 06, 2017
    There is significant heterogeneity amongst individuals with Autism Spectrum Disorder (ASD) in symptom presentation and severity. An understanding of the factors that contribute to and modulate symptom severity are critical to informing prognosis, stratification, and treatment decisions. Maternal prenatal stress exposure is a nonspecific risk factor for a wide array of neurodevelopmental outcomes in subsequent offspring. Emerging evidence suggests that prenatal maternal stress may increase ASD risk and contribute to variability in autism‐like traits in the general population. In the current study, we aimed to determine whether prenatal maternal exposure to stressful life events is associated with symptom severity amongst individuals with ASD. We performed multiple regression analyses to examine associations between retrospectively recalled maternal prenatal stressful life events and the severity of ASD‐associated symptoms in 174 children with ASD (Mage = 9.09 years; SD = 3.81). ASD‐related symptom severity was measured using the Social Responsiveness Scale and communication abilities were measured using the Children's Communication Checklist. Exposure to prenatal stressful life events was a significant predictor of ASD‐related symptom severity (t = 2.014; P = .048) and communication abilities (t = −2.925; P = .004) amongst children with ASD, even after controlling for a range of sociodemographic and obstetric variables. Follow‐up analyses demonstrated significant increases in symptom severity only in the context of multiple (two or more) prenatal stressful life events. Together, these findings indicate that ASD, in the context of prenatal maternal stress exposure, may be associated with a more severe phenotype, particularly when there are multiple prenatal exposures. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    July 06, 2017   doi: 10.1002/aur.1830   open full text
  • Associations of endocrine stress‐related gene polymorphisms with risk of autism spectrum disorders: Evidence from an integrated meta‐analysis.
    Ping‐yuan Yang, Ya‐jing Menga, Tao Li, Yi Huang.
    Autism Research. June 28, 2017
    Autism spectrum disorders (ASD) are related to serotonin transporter (5‐HTT) and catechol‐O‐methyl transferase (COMT) as two most monoaminergic polymorphic variations. However, multiple studies assessing rs4680 and 5‐HTTLPR variants in ASD have reported inconsistent results. Therefore, we conducted an integrated meta‐analysis to combine case‐control and transmission/disequilibrium test (TDT) studies to determine whether COMT and 5‐HTT are associated with ASD. We searched multiple electronic databases (PubMed, EmBase and Web of Science) to identify studies assessing the rs4680 and 5‐HTTLPR variants in ASD from Jan 1997 to Dec 2016. Then allelic data from case–control and TDT studies were analyzed by the Catmap package in the R software. A total of 5 studies were eligible for the meta‐analysis of rs4680, including 3 case–control, 1 TDT and 1 TDT & case–control studies. Meanwhile, 22 studies of 5‐HTTLPR were available, including 16 TDT, 4 case–control and 2 TDT & case–control studies. The current meta‐analysis included 814 ASD cases, 741 controls and 311 families related to rs4680; 749 ASD cases, 1,118 controls and 1,861 families relevant to 5‐HTTLPR were also evaluated. For rs4680, the pooled OR was 1.18 (95% CI = 0.87–1.59, P = 0.29, Pheterogeneity < 0.00001). There was no significant association of rs4680 with risk of ASD between the two subgroups. For 5‐HTTLPR, the pooled OR was 1.05 (95% CI = 0.92–1.20, P = 0.4652, Pheterogeneity < 0.00001). Meanwhile, we found no significant risk in individual case–control or TDT studies. The above findings indicated that neither COMT rs4680 nor 5‐HTT 5‐HTTLPR polymorphism significantly affects ASD risk. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 28, 2017   doi: 10.1002/aur.1822   open full text
  • Auditory processing in autism spectrum disorder: Mismatch negativity deficits.
    Chantal Vlaskamp, Bob Oranje, Gitte Falcher Madsen, Jens Richardt Møllegaard Jepsen, Sarah Durston, Cathriona Cantio, Birte Glenthøj, Niels Bilenberg.
    Autism Research. June 22, 2017
    Children with autism spectrum disorders (ASD) often show changes in (automatic) auditory processing. Electrophysiology provides a method to study auditory processing, by investigating event‐related potentials such as mismatch negativity (MMN) and P3a‐amplitude. However, findings on MMN in autism are highly inconsistent, partly due to small sample sizes in the studies and differences in MMN paradigms. Therefore, in the current study, MMN and P3a amplitude were assessed in a relatively large sample of children with ASD, using a more extensive MMN paradigm and compared with that of typically developing children (TDC). Thirty‐five children (aged 8–12 years) with ASD and 38 age and gender matched TDC were assessed with a MMN paradigm with three types of deviants, i.e., frequency, duration and a combination of these two. MMN elicited by duration and frequency‐duration deviants was significantly reduced in the ASD group. P3a‐amplitude elicited by duration deviants was significantly increased in the ASD group. Reduced MMN in children with ASD suggests that children with ASD may be less responsive to environmentally deviant stimuli at an early (sensory) level. P3a‐amplitude was increased in ASD, implying a hyper‐responsivity at the attentional level. In addition, as similar MMN deficits are found in schizophrenia, these MMN results may explain some of the frequently reported increased risk of children with ASD to develop schizophrenia later in life. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 22, 2017   doi: 10.1002/aur.1821   open full text
  • Validating the social responsiveness scale for adults with autism.
    Wai Chan, Leann E. Smith, Jinkuk Hong, Jan S. Greenberg, Marsha R. Mailick.
    Autism Research. June 22, 2017
    The Social Responsiveness Scale [SRS; Constantino & Gruber, 2005] is a widely‐used measure of autism symptoms, but its application for the study of adults with autism spectrum disorders has not been fully evaluated. Using a factor structure consistent with The Diagnostic and Statistical Manual of Mental Disorders (5th ed., DSM‐V) criteria for autism spectrum disorder [Frazier et al., 2014], the primary purpose of the current study was to establish the validity of the SRS with a sample of adults with autism spectrum disorder (N = 237). Correlational analyses indicated that SRS factors were highly associated with autism symptoms and behavioral measures, indicating concurrent and predictive validity. Multiple regression results demonstrated that SRS factors were differentially related to measures specific to social or behavioral domains, indicating convergent and discriminant validity. Implications for future research are discussed. Autism Res 2017, 10: 1663–1671. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 22, 2017   doi: 10.1002/aur.1813   open full text
  • The influence of parental concern on the utility of autism diagnostic instruments.
    Karoline Alexandra Havdahl, Somer L. Bishop, Pål Surén, Anne‐Siri Øyen, Catherine Lord, Andrew Pickles, Stephen von Tetzchner, Synnve Schjølberg, Nina Gunnes, Mady Hornig, W. Ian Lipkin, Ezra Susser, Michaeline Bresnahan, Per Magnus, Nina Stenberg, Ted Reichborn‐Kjennerud, Camilla Stoltenberg.
    Autism Research. June 22, 2017
    The parental report‐based Autism Diagnostic Interview‐Revised (ADI‐R) and the clinician observation‐based Autism Diagnostic Observation Schedule (ADOS) have been validated primarily in U.S. clinics specialized in autism spectrum disorder (ASD), in which most children are referred by their parents because of ASD concern. This study assessed diagnostic agreement of the ADOS‐2 and ADI‐R toddler algorithms in a more broadly based sample of 679 toddlers (age 35–47 months) from the Norwegian Mother and Child Cohort. We also examined whether parental concern about ASD influenced instrument performance, comparing toddlers identified based on parental ASD concern (n = 48) and parent‐reported signs of developmental problems (screening) without a specific concern about ASD (n = 400). The ADOS cutoffs showed consistently well‐balanced sensitivity and specificity. The ADI‐R cutoffs demonstrated good specificity, but reduced sensitivity, missing 43% of toddlers whose parents were not specifically concerned about ASD. The ADI‐R and ADOS dimensional scores agreed well with clinical diagnoses (area under the curve ≥ 0.85), contributing additively to their prediction. On the ADI‐R, different cutoffs were needed according to presence or absence of parental ASD concern, in order to achieve comparable balance of sensitivity and specificity. These results highlight the importance of taking parental concern about ASD into account when interpreting scores from parental report‐based instruments such as the ADI‐R. While the ADOS cutoffs performed consistently well, the additive contributions of ADI‐R and ADOS scores to the prediction of ASD diagnosis underscore the value of combining instruments based on parent accounts and clinician observation in evaluation of ASD. Autism Res 2017, 10: 1672–1686. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 22, 2017   doi: 10.1002/aur.1817   open full text
  • Audition‐specific temporal processing deficits associated with language function in children with autism spectrum disorder.
    Jennifer H. Foss‐Feig, Kimberly B. Schauder, Alexandra P. Key, Mark T. Wallace, Wendy L. Stone.
    Autism Research. June 20, 2017
    Sensory processing alterations are highly prevalent in autism spectrum disorder (ASD). Neurobiologically‐based theories of ASD propose that abnormalities in the processing of temporal aspects of sensory input could underlie core symptoms of ASD. For example, rapid auditory temporal processing is critical for speech perception, and language difficulties are central to the social communication deficits defining the disorder. This study assessed visual and auditory temporal processing abilities and tested their relation to core ASD symptoms. 53 children (26 ASD, 27 TD) completed visual and auditory psychophysical gap detection tasks to measure gap detection thresholds (i.e., the minimum interval between sequential stimuli needed for individuals to perceive an interruption between the stimuli) in each domain. Children were also administered standardized language assessments such that the relation between individual differences in auditory gap detection thresholds and degree of language and communication difficulties among children with ASD could be assessed. Children with ASD had substantially higher auditory gap detection thresholds compared to children with TD, and auditory gap detection thresholds were correlated significantly with several measures of language processing in this population. No group differences were observed in the visual temporal processing. Results indicate a domain‐specific impairment in rapid auditory temporal processing in ASD that is associated with greater difficulties in language processing. Findings provide qualified support for temporal processing theories of ASD and highlight the need for future research testing the nature, extent, and universality of auditory temporal processing deficits in this population. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 20, 2017   doi: 10.1002/aur.1820   open full text
  • Reward learning modulates the attentional processing of faces in children with and without autism spectrum disorder.
    Tianbi Li, Xueqin Wang, Junhao Pan, Shuyuan Feng, Mengyuan Gong, Yaxue Wu, Guoxiang Li, Sheng Li, Li Yi.
    Autism Research. June 12, 2017
    The processing of social stimuli, such as human faces, is impaired in individuals with autism spectrum disorder (ASD), which could be accounted for by their lack of social motivation. The current study examined how the attentional processing of faces in children with ASD could be modulated by the learning of face‐reward associations. Sixteen high‐functioning children with ASD and 20 age‐ and ability‐matched typically developing peers participated in the experiments. All children started with a reward learning task, in which the children were presented with three female faces that were attributed with positive, negative, and neutral values, and were required to remember the faces and their associated values. After this, they were tested on the recognition of the learned faces and a visual search task in which the learned faces served as the distractor. We found a modulatory effect of the face‐reward associations on the visual search but not the recognition performance in both groups despite the lower efficacy among children with ASD in learning the face‐reward associations. Specifically, both groups responded faster when one of the distractor faces was associated with positive or negative values than when the distractor face was neutral, suggesting an efficient attentional processing of these reward‐associated faces. Our findings provide direct evidence for the perceptual‐level modulatory effect of reward learning on the attentional processing of faces in individuals with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 12, 2017   doi: 10.1002/aur.1823   open full text
  • Behavioral abnormalities in the Fmr1‐KO2 mouse model of fragile X syndrome: The relevance of early life phases.
    Julie Gaudissard, Melanie Ginger, Marika Premoli, Maurizio Memo, Andreas Frick, Susanna Pietropaolo.
    Autism Research. June 07, 2017
    Fragile X syndrome (FXS) is a developmental disorder caused by a mutation in the X‐linked FMR1 gene, coding for the FMRP protein which is largely involved in synaptic function. FXS patients present several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper‐responsiveness, and cognitive deficits. Autistic symptoms, e.g., altered social interaction and communication, are also often observed: FXS is indeed the most common monogenic cause of autism. Mouse models of FXS are therefore of great interest for research on both FXS and autistic pathologies. The Fmr1‐KO2 mouse line is the most recent FXS model, widely used for brain studies; surprisingly, little is known about the face validity of this model, i.e., its FXS‐like behavioral phenotype. Furthermore, no data are available for the age‐related expression of the pathological phenotypes in this mouse line, a critical issue for modelling neurodevelopmental disorders. Here we performed an extensive behavioral characterization of the KO2 model at infancy, adolescent and adult ages. Hyperactivity, altered emotionality, sensory hyper‐responsiveness and memory deficits were already present in KO mice at adolescence and remained evident at adulthood. Alterations in social behaviors were instead observed only in young KO animals: during the first 2 weeks of life, KOs emitted longer ultrasonic vocalizations compared to their WT littermates and as adolescents they displayed more aggressive behaviors towards a conspecific. These results strongly support the face validity of the KO2 mouse as a model for FXS, at the same time demonstrating that its ability to recapitulate social autistic‐relevant phenotypes depends on early testing ages. Autism Res 2017, 10: 1584–1596. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 07, 2017   doi: 10.1002/aur.1814   open full text
  • Evaluating the importance of social motor synchronization and motor skill for understanding autism.
    Paula Fitzpatrick, Veronica Romero, Joseph L. Amaral, Amie Duncan, Holly Barnard, Michael J. Richardson, R. C. Schmidt.
    Autism Research. June 07, 2017
    Impairments in social interaction and communicating with others are core features of autism spectrum disorder (ASD), but the specific processes underlying such social competence impairments are not well understood. An important key for increasing our understanding of ASD‐specific social deficits may lie with the social motor synchronization that takes place when we implicitly coordinate our bodies with others. Here, we tested whether dynamical measures of synchronization differentiate children with ASD from controls and further explored the relationships between synchronization ability and motor control problems. We found (a) that children with ASD exhibited different and less stable patterns of social synchronization ability than controls; (b) children with ASD performed motor movements that were slower and more variable in both spacing and timing; and (c) some social synchronization that involved motor timing was related to motor ability but less rhythmic synchronization was not. These findings raise the possibility that objective dynamical measures of synchronization ability and motor skill could provide new insights into understanding the social deficits in ASD that could ultimately aid clinical diagnosis and prognosis. Autism Res 2017, 10: 1687–1699. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 07, 2017   doi: 10.1002/aur.1808   open full text
  • Cross‐site randomized control trial of the Social ABCs caregiver‐mediated intervention for toddlers with autism spectrum disorder.
    Jessica A. Brian, Isabel M. Smith, Lonnie Zwaigenbaum, Susan E. Bryson.
    Autism Research. June 02, 2017
    To evaluate the efficacy of the Social ABCs parent‐mediated intervention for toddlers with suspected or confirmed autism spectrum disorder (ASD), through a cross‐site randomized control trial, sixty‐three parent–toddler dyads (toddler age: 16–30 months) were randomized into treatment (Social ABCs) or control (service‐as‐usual) conditions. Video data were obtained at three key time‐points: Baseline; Post‐training (PT; week 12); and Follow‐Up (week 24). Analyses included 62 dyads. Treatment allocation significantly accounted for PT gains, all favouring the Treatment group, in (1) child functional vocal responsiveness to parent prompts (R2 = 0.43, P < .001), (2) child vocal initiations (R2 = 0.28, P < .001), (3) parent smiling (R2 = 0.09, P = .017), and (4) fidelity of implementation (R2 = 0.71, P < .001). A trend was observed for increased social orienting (R2 = 0.06, P = 0.054); gains in parent smiling significantly predicted increases in child smiling and social orienting. Parents in the treatment condition reported significant gains in self‐efficacy following the intervention (P = 0.009). No differential effects emerged for performance on standardized measures. The Social ABCs is a relatively low‐resource, efficacious intervention, with potential to be a cost‐effective means of intervening at the first signs of possible ASD. Autism Res 2017, 10: 1700–1711. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Clinical Trial Title: Social ABCs for Toddlers with Signs of Autism Spectrum Disorder: RCT of a Parent‐Mediated Intervention http// identifier: NCT02428452.
    June 02, 2017   doi: 10.1002/aur.1818   open full text
  • The measurement properties of the spence children's anxiety scale‐parent version in a large international pooled sample of young people with autism spectrum disorder.
    Iliana Magiati, Jian Wei Lerh, Matthew J. Hollocks, Mirko Uljarevic, Jacqui Rodgers, Helen McConachie, Ann Ozsivadjian, Mikle South, Amy Van Hecke, Antonio Hardan, Robin Libove, Susan Leekam, Emily Simonoff.
    Autism Research. June 02, 2017
    Anxiety‐related difficulties are common in ASD, but measuring anxiety reliably and validly is challenging. Despite an increasing number of studies, there is no clear agreement on which existing anxiety measure is more psychometrically sound and what is the factor structure of anxiety in ASD. The present study examined the internal consistency, convergent, divergent, and discriminant validity, as well as the factor structure of the Spence Children's Anxiety Scale‐Parent Version (SCAS‐P), in a large international pooled sample of 870 caregivers of youth with ASD from 12 studies in the United Kingdom, United States, and Singapore who completed the SCAS‐P. Most were community recruited, while the majority had at least one measure of ASD symptomatology and either cognitive or adaptive functioning measures completed. Existing SCAS‐P total scale and subscales had excellent internal consistency and good convergent, divergent and discriminant validity similar to or better than SCAS‐P properties reported in typically developing children, except for the poorer internal consistency of the physical injury subscale. Confirmatory Factor Analysis (CFA) of the existing SCAS‐P six‐correlated factor structure was a poor fit for this pooled database. Principal component analysis using half of the pooled sample identified a 30‐item five correlated factor structure, but a CFA of this PCA‐derived structure in the second half of this pooled sample revealed a poor fit, although the PCA‐derived SCAS‐P scale and subscales had stronger validity and better internal consistency than the original SCAS‐P. The study's limitations, the use of the SCAS‐P to screen for DSM‐derived anxiety problems in ASD and future research directions are discussed. Autism Res 2017, 10: 1629–1652. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 02, 2017   doi: 10.1002/aur.1809   open full text
  • Sex differences in parent‐reported executive functioning and adaptive behavior in children and young adults with autism spectrum disorder.
    Emily I. White, Gregory L. Wallace, Julia Bascom, Anna C. Armour, Kelly Register‐Brown, Haroon S. Popal, Allison B. Ratto, Alex Martin, Lauren Kenworthy.
    Autism Research. June 01, 2017
    This study is the largest to date examining executive function and adaptive skills in females with autism spectrum disorder (ASD). Its primary aim was to utilize parent ratings of real‐world executive functioning and adaptive behavior to better understand whether females with ASD differ from males with ASD in these areas of everyday functioning. We compared 79 females with ASD to 158 males with ASD (ages 7–18) who were statistically matched on age, IQ, and level of ADHD or ASD traits. All participants were assessed using the Behavior Rating Inventory of Executive Function (BRIEF) and a subset (56 females and 130 males) also received the Vineland Adaptive Behavior Scales (VABS). Females were rated by parents as having greater problems with executive function on the BRIEF. Parents also rated females as exhibiting more difficulties than males on the Daily Living Skills domain of the VABS. There was a correlation between increased global EF difficulty and decreased adaptive ability in both males and females. Our results indicate relative weaknesses for females compared to males diagnosed with ASD on executive function and daily living skills. These differences occur in the absence of sex differences in our sample in age, IQ, clinician ratings of core ASD symptomatology, parent ratings of ADHD symptoms, and parent‐reported social and communication adaptive skills on the VABS. These findings indicate specific liabilities in real world EF and daily living skills for females with ASD and have important implications for targeting their treatments. Autism Res 2017, 10: 1653–1662. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    June 01, 2017   doi: 10.1002/aur.1811   open full text
  • Prevalence of autism spectrum disorder and autistic symptoms in a school‐based cohort of children in Kolkata, India.
    Alokananda Rudra, Matthew K. Belmonte, Parmeet Kaur Soni, Saoni Banerjee, Shaneel Mukerji, Bhismadev Chakrabarti.
    Autism Research. May 25, 2017
    Despite housing ∼18% of the world's population, India does not yet have an estimate of prevalence of autism. This study was carried out to estimate the prevalence of autism in a selected population of school‐children in India. N = 11,849 children (mean age = 5.9 [SD = 1.3], 39.5% females) were selected from various school types from three boroughs in Kolkata, India. Parents/caregivers and teachers filled in the social and communication disorders checklist (SCDC). Children meeting cutoff on parent‐reported SCDC were followed up with the social communication questionnaire (SCQ). SCQ‐positive children were administered the autism diagnostic observation schedule (ADOS). Teacher report on SCDC was available on all 11,849 children. Parent‐report SCDC scores were obtained for 5,947 children. Mean scores on teacher SCDC were significantly lower than parent SCDC. Out of 1,247 SCDC‐positive children, 882 answered the SCQ, of whom 124 met the cutoff score of 15. Six of these children met criteria for autism, autism spectrum disorder (ASD), or broader autism spectrum on the ADOS. The weighted estimate of supra‐threshold SCQ scores was 3.54% (CI: 2.88–4.3%). The weighted prevalence estimate of positive scores (for broader autism spectrum + ASD + autism) was 0.23% (0.07–0.46%). As ∼20% children in this state are known to be out of the school system, and ASD prevalence is likely to be higher in this group, this estimate is likely to represent the lower‐bound of the true prevalence. This study provides preliminary data on the prevalence of broader‐spectrum autism and supra‐threshold autistic traits in a population sample of school children in Eastern India. Autism Res 2017, 10: 1597–1605. ©2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    May 25, 2017   doi: 10.1002/aur.1812   open full text
  • White matter compromise in autism? Differentiating motion confounds from true differences in diffusion tensor imaging.
    Seraphina K. Solders, Ruth A. Carper, Ralph‐Axel Müller.
    Autism Research. May 15, 2017
    Common findings from diffusion tensor imaging (DTI) in autism spectrum disorder (ASD) include reduced fractional anisotropy (FA), and increased mean and radial diffusivity (MD, RD) of white matter tracts. However, findings may be confounded by head motion. We examined how group‐level motion matching affects DTI comparisons between ASD and typically developing (TD) groups. We included 57 ASD and 50 TD participants, comparing three subsets at increasing levels of motion‐matching stringency: full sample (FS); quality‐controlled (QC); and quantitatively‐matched (QM). Groups were compared on diffusivity measures using Tract‐Based Spatial Statistics (TBSS) and probabilistic tractography. Two methods for estimating diffusivity were compared: dti‐fit and restore. TBSS: In set FS, FA was reduced in the ASD compared to the TD group throughout the right hemisphere. This effect was less extensive in set QC and absent in set QM. However, effect sizes remained stable or increased with better quality‐control in some regions. Tractography: In set QM, MD was significantly higher in ASD overall and RD was higher in bilateral ILF. Effects were more robust in QM than in FS or QC sets. Effect sizes in several tracts increased with stringent quality matching. Restore improved tensor estimates, with some increases in effect sizes, but did not fully compensate for reduced quality. Findings suggest that some previously reported DTI findings for ASD may have been confounded by motion. However, effects in the tightly matched subset indicate that tract‐specific anomalies probably do exist in ASD. Our results highlight the need for careful quality‐control and motion‐matching. Autism Res 2017, 10: 1606–1620. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    May 15, 2017   doi: 10.1002/aur.1807   open full text
  • Developmental functioning and medical Co‐morbidity profile of children with complex and essential autism.
    Jaimie Flor, Jayne Bellando, Maya Lopez, Amy Shui.
    Autism Research. May 05, 2017
    Children with Autism Spectrum Disorders (ASD) may be characterized as “complex” (those with microcephaly and/or dysmorphology) or “essential” (those with neither of these two). Previous studies found subjects in the complex group exhibited lower IQ scores, poorer response to behavioral intervention, more seizures and more abnormal EEGs and brain MRIs compared to the essential group. The objective of this study was to determine if there are differences in complex versus essential subjects based on several developmental/psychological measures as well as certain medical comorbidities. This study utilized data from 1,347 individuals (2–17 years old) well‐characterized subjects enrolled in Autism Treatment Network (ATN) Registry. Head circumference measurement and the Autism Dysmorphology Measure (ADM) were used by trained physicians to classify subjects as complex or essential. Significantly lower scores were seen for complex subjects in cognitive level, adaptive behavior and quality of life. Complex subjects showed significantly increased physician‐documented GI symptoms and were on a higher number of medications. No significant differences in autism severity scores, behavioral ratings and parent‐reported sleep problems were found. After adjusting for multiple comparisons made, adaptive scores remained significantly lower for the complex group, and the complex group used a significantly higher number of medications and had increased GI symptoms. Complex and essential autism subtypes may have distinct developmental and medical correlates and thus underlines the importance of looking for microcephaly and dysmorphology, when evaluating a child with autism. Determining this distinction in autism may have implications in prognosis, identifying medical co‐morbidities, directing diagnostic evaluations and treatment interventions. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    May 05, 2017   doi: 10.1002/aur.1779   open full text
  • Identifying the clinical needs and patterns of health service use of adolescent girls and women with autism spectrum disorder.
    Ami Tint, Jonathan A. Weiss, Yona Lunsky.
    Autism Research. May 05, 2017
    Girls and women in the general population present with a distinct profile of clinical needs and use more associated health services compared to boys and men; however, research focused on health service use patterns among girls and women with Autism Spectrum Disorder (ASD) is limited. In the current study, caregivers of 61 adolescent girls and women with ASD and 223 boys and men with ASD completed an online survey. Descriptive analyses were conducted to better understand the clinical needs and associated service use patterns of girls and women with ASD. Sex/gender comparisons were made of individuals’ clinical needs and service use. Adolescent girls and women with ASD had prevalent co‐occurring mental and physical conditions and parents reported elevated levels of caregiver strain. Multiple service use was common across age groups, particularly among adolescent girls and women with intellectual disability. Overall, few sex/gender differences emerged, although a significantly greater proportion of girls and women accessed psychiatry and emergency department services as compared to boys and men. Though the current study is limited by its use of parent report and small sample size, it suggests that girls and women with ASD may share many of the same high clinical needs and patterns of services use as boys and men with ASD. Areas for future research are discussed to help ensure appropriate support is provided to this understudied population. Autism Res 2017, 10: 1558–1566. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    May 05, 2017   doi: 10.1002/aur.1806   open full text
  • Atypical perception in autism: A failure of perceptual specialization?
    Bat Sheva Hadad, Eugenia K. Goldstein, Natalie N. Russo.
    Autism Research. May 05, 2017
    We examined whether reduced perceptual specialization underlies atypical perception in autism spectrum disorder (ASD) testing classifications of stimuli that differ either along integral dimensions (prototypical integral dimensions of value and chroma), or along separable dimensions (prototypical separable dimensions of value and size). Current models of the perception of individuals with an ASD would suggest that on these tasks, individuals with ASD would be as, or more, likely to process dimensions as separable, regardless of whether they represented separable or integrated dimensions. In contrast, reduced specialization would propose that individuals with ASD would respond in a more integral manner to stimuli that differ along separable dimensions, and at the same time, respond in a more separable manner to stimuli that differ along integral dimensions. A group of nineteen adults diagnosed with high functioning ASD and seventeen typically developing participants of similar age and IQ, were tested on speeded and restricted classifications tasks. Consistent with the reduced specialization account, results show that individuals with ASD do not always respond more analytically than typically developed (TD) observers: Dimensions identified as integral for TD individuals evoke less integral responding in individuals with ASD, while those identified as separable evoke less analytic responding. These results suggest that perceptual representations are more broadly tuned and more flexibly represented in ASD. Autism Res 2017, 10: 1510–1522. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    May 05, 2017   doi: 10.1002/aur.1800   open full text
  • Social skills training for children with autism spectrum disorder using a robotic behavioral intervention system.
    Sang‐Seok Yun, JongSuk Choi, Sung‐Kee Park, Gui‐Young Bong, HeeJeong Yoo.
    Autism Research. May 02, 2017
    We designed a robot system that assisted in behavioral intervention programs of children with autism spectrum disorder (ASD). The eight‐session intervention program was based on the discrete trial teaching protocol and focused on two basic social skills: eye contact and facial emotion recognition. The robotic interactions occurred in four modules: training element query, recognition of human activity, coping‐mode selection, and follow‐up action. Children with ASD who were between 4 and 7 years old and who had verbal IQ ≥ 60 were recruited and randomly assigned to the treatment group (TG, n = 8, 5.75 ± 0.89 years) or control group (CG, n = 7; 6.32 ± 1.23 years). The therapeutic robot facilitated the treatment intervention in the TG, and the human assistant facilitated the treatment intervention in the CG. The intervention procedures were identical in both groups. The primary outcome measures included parent‐completed questionnaires, the Autism Diagnostic Observation Schedule (ADOS), and frequency of eye contact, which was measured with the partial interval recording method. After completing treatment, the eye contact percentages were significantly increased in both groups. For facial emotion recognition, the percentages of correct answers were increased in similar patterns in both groups compared to baseline (P > 0.05), with no difference between the TG and CG (P > 0.05). The subjects’ ability to play, general behavioral and emotional symptoms were significantly diminished after treatment (p < 0.05). These results showed that the robot‐facilitated and human‐facilitated behavioral interventions had similar positive effects on eye contact and facial emotion recognition, which suggested that robots are useful mediators of social skills training for children with ASD. Autism Res 2017,. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1306–1323. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    May 02, 2017   doi: 10.1002/aur.1778   open full text
  • Long‐term memory in older children/adolescents and adults with autism spectrum disorder.
    Diane L. Williams, Nancy J. Minshew, Gerald Goldstein, Carla A. Mazefsky.
    Autism Research. April 27, 2017
    This study extends prior memory reports in autism spectrum disorders (ASD) by investigating memory for narratives after longer recall periods and by examining developmental aspects of narrative memory using a cross‐sectional design. Forty‐seven older children/adolescents with ASD and 31 youth with typical development (TD) and 39 adults with ASD and 45 TD adults were compared on memory for stories from standardized measures appropriate for each age group at three intervals (immediate, 30 min, and 2 day). Both the youth with and without ASD had difficulty with memory for story details with increasing time intervals. More of the youths with ASD performed in the range of impairment when recalling the stories 2 days later as compared to the TD group. The adults with ASD had more difficulty on memory for story details with increasing delay and were poorer at recall of thematic information (needed to create a gist) across the three delay conditions as compared to the TD group. Analyses of the individual results suggested that memory for details of most of the adults with ASD was not impaired when applying a clinical standard; however, a significant percentage of the adults with ASD did not make use of thematic information to organize the narrative information, which would have helped them to remember the stories. The youth with and without ASD performed similarly when both were at a stage of development when memory for details is the primary strategy. The adults with ASD had difficulty with use organizational strategies to support episodic memory. Autism Res 2017, 10: 1523–1532. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 27, 2017   doi: 10.1002/aur.1801   open full text
  • Autism: Too eager to learn? Event related potential findings of increased dependency on intentional learning in a serial reaction time task.
    Fenny S. Zwart, Constance Th.W.M. Vissers, Roemer van der Meij, Roy P.C. Kessels, Joseph H.R. Maes.
    Autism Research. April 27, 2017
    It has been suggested that people with autism spectrum disorder (ASD) have an increased tendency to use explicit (or intentional) learning strategies. This altered learning may play a role in the development of the social communication difficulties characterizing ASD. In the current study, we investigated incidental and intentional sequence learning using a Serial Reaction Time (SRT) task in an adult ASD population. Response times and event related potentials (ERP) components (N2b and P3) were assessed as indicators of learning and knowledge. Findings showed that behaviorally, sequence learning and ensuing explicit knowledge were similar in ASD and typically developing (TD) controls. However, ERP findings showed that learning in the TD group was characterized by an enhanced N2b, while learning in the ASD group was characterized by an enhanced P3. These findings suggest that learning in the TD group might be more incidental in nature, whereas learning in the ASD group is more intentional or effortful. Increased intentional learning might serve as a strategy for individuals with ASD to control an overwhelming environment. Although this led to similar behavioral performances on the SRT task, it is very plausible that this intentional learning has adverse effects in more complex social situations, and hence contributes to the social impairments found in ASD. Autism Res 2017, 10: 1533–1543. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 27, 2017   doi: 10.1002/aur.1802   open full text
  • The joint effect of air pollution exposure and copy number variation on risk for autism.
    Dokyoon Kim, Heather Volk, Santhosh Girirajan, Sarah Pendergrass, Molly A. Hall, Shefali S. Verma, Rebecca J. Schmidt, Robin L. Hansen, Debashis Ghosh, Yunin Ludena‐Rodriguez, Kyoungmi Kim, Marylyn D. Ritchie, Irva Hertz‐Picciotto, Scott B. Selleck.
    Autism Research. April 27, 2017
    Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population‐based case‐control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable‐copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child's CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P < 0.005) much greater than the increased risks associated with either genomic duplication (OR 1.85, 95% CI 1.25–2.73) or ozone (OR 1.20, 95% CI 0.93–1.54) alone. Similar results were obtained when CNV and ozone were dichotomized to compare those in the top quartile relative to those having a smaller CNV burden and lower exposure to ozone, and when exposures were assessed separately for pregnancy, the first year of life, and the second year of life. No interactions were observed for other air pollutants, even those that demonstrated main effects; ozone tends to be negatively correlated with the other pollutants examined. While earlier work has demonstrated interactions between the presence of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these findings appear to be the first indication that global copy number variation may increase susceptibility to certain environmental factors, and underscore the need to consider both genomics and environmental exposures as well as the mechanisms by which each may amplify the risks for autism associated with the other. Autism Res 2017, 10: 1470–1480. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 27, 2017   doi: 10.1002/aur.1799   open full text
  • Global and local visual processing in autism: An objective assessment approach.
    Kritika Nayar, Angela C. Voyles, Lynne Kiorpes, Adriana Di Martino.
    Autism Research. April 22, 2017
    We examined global and local visual processing in autism spectrum disorder (ASD) via a match‐to‐sample task using Kanizsa illusory contours (KIC). School‐aged children with ASD (n = 28) and age‐matched typically developing controls (n = 22; 7–13 years) performed a sequential match‐to‐sample between a solid shape (sample) and two illusory alternatives. We tracked eye gaze and behavioral performance in two task conditions: one with and one without local interference from background noise elements. While analyses revealed lower accuracy and longer reaction time in ASD in the condition with local interference only, eye tracking robustly captured ASD‐related global atypicalities across both conditions. Specifically, relative to controls, children with ASD showed decreased fixations to KIC centers, indicating reduced global perception. Notably, they did not differ from controls in regard to fixations to local elements or touch response location. These results indicate impaired global perception in the absence of heightened local processing in ASD. They also underscore the utility of eye‐tracking measures as objective indices of global/local visual processing strategies in ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 22, 2017   doi: 10.1002/aur.1782   open full text
  • Internal noise estimates correlate with autistic traits.
    Greta Vilidaite, Miaomiao Yu, Daniel H. Baker.
    Autism Research. April 17, 2017
    Previous neuroimaging research has reported increased internal (neural) noise in sensory systems of autistic individuals. However, it is unclear if this difference has behavioural or perceptual consequences, as previous attempts at measuring internal noise in ASD psychophysically have been indirect. Here, we use a “gold standard” psychophysical double‐pass paradigm to investigate the relationship between internal noise and autistic traits in the neurotypical population (n = 43). We measured internal noise in three tasks (contrast perception, facial expression intensity perception, and number summation) to estimate a global internal noise factor using principal components analysis. This global internal noise was positively correlated with autistic traits (rs = 0.32, P = 0.035). This suggests that increased internal noise is associated with the ASD phenotype even in subclinical populations. The finding is discussed in relation to the neural and genetic basis of internal noise in ASD. Autism Res 2017,. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 17, 2017   doi: 10.1002/aur.1781   open full text
  • The Social Communication Questionnaire for adults with intellectual disability: SCQ‐AID.
    Olivia Derks, Manuel Heinrich, Whitney Brooks, Paula Sterkenburg, Jane McCarthy, Lisa Underwood, Tanja Sappok.
    Autism Research. April 12, 2017
    Autism spectrum disorder (ASD) frequently co‐occurs with intellectual disability (ID) and often remains undiagnosed until adulthood. The Social Communication Questionnaire (SCQ) is a widely used measure to screen for ASD. To improve the utility of the SCQ for adults with ID, the aim of this study was to develop an ID‐specific and adult appropriate algorithm for the SCQ using a core set of valid items. These items were identified in one sample (N = 226) and further cross‐validated in a second, independent sample (N = 225) from Germany, England and the U.S. The newly developed algorithm has 24 items compared with the 40 items in the original instrument. The reduced item core set yielded similar diagnostic validity as the original algorithm with good sensitivity values (0.81–0.89) and low specificity values (0.62–0.72). Overall, these results suggest that the removed items may not carry diagnostically relevant information in adults with ID; thus, excluding these items may result in a more efficient and age‐appropriate screening measure for this population. However, due to the low specificity values, a comprehensive assessment is essential for a final diagnostic assignment. Autism Res 2017, 10: 1481–1490. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 12, 2017   doi: 10.1002/aur.1795   open full text
  • Placebo‐like response in absence of treatment in children with Autism.
    Rebecca M. Jones, Caroline Carberry, Amarelle Hamo, Catherine Lord.
    Autism Research. April 12, 2017
    Caregiver report is the most common measure of change in pediatric psychiatry. Yet, placebo response rates pose significant challenges to reliably detect a treatment response. The present study simulated an eight‐week clinical trial protocol for Autism Spectrum Disorder (ASD) for the purpose of testing the feasibility and validity of several outcome measures. Twenty caregivers answered questions about their child's behavior on their smartphone each week and completed a battery of paper questionnaires during weeks one and eight. No treatment was administered. Caregivers reported a significant decrease in problem behaviors on the Aberrant Behavior Checklist (ABC) (29% decrease) and general ASD behaviors on the Social Responsiveness Scale (SRS) (7% decrease). There was also a trend of behavior improvement from smartphone questions but no significant changes in clinical ratings of core diagnostic features of ASD. Participation in a comprehensive protocol in the absence of a particular treatment significantly influenced how caregivers perceived the severity of their children's problem behaviors. These placebo‐like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual and have implications for future behavioral and pharmacological treatment trial designs. Autism Res 2017, 10: 1567–1572. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 12, 2017   doi: 10.1002/aur.1798   open full text
  • Assessment of presentation patterns, clinical severity, and sensorial mechanism of tip‐toe behavior in severe ASD subjects with intellectual disability: A cohort observational study.
    Giulio Valagussa, Luca Trentin, Valeria Balatti, Enzo Grossi.
    Autism Research. April 06, 2017
    We assessed presentation patterns and characteristics of tip‐toe behavior (TTB), more commonly known as toe walking, in a cohort of severe autism spectrum disorder (ASD) subjects with intellectual disability in two studies. The first study included 69 consecutive ASD subjects (57 males, mean age = 14 years—3.7 SD) under observation at our institute. A therapist assessed the presence of TTB during standing, walking, and running through direct observation and an interview with the subjects main caregiver. The prevalence of TTB was 32%. We found three clinical presentation patterns of TTB: (1) present when standing, walking and running (45.5%), (2) present when walking and running (18.4%), or (3) present only when running (36.4%). TTB subjects were more frequently nonverbal than those without TTB (72.7% vs. 44.6%‐P = 0.03). On the other hand, no significant difference in ASD severity according to the ADOS scale was found between TTB and non‐TTB subjects. In the second study, carried out in a subgroup of 14 ASD subjects (7 TTB and 7 non‐TTB), we evidenced that a soft floor surface (foam mats) made a substantial difference in reducing the TTB phenomenon. TTB is frequently present in ASD individuals and may occur in three mutually exclusive modalities, which ultimately defines what is commonly known as toe walking. The presence of TTB seems correlated to the severity of language delay. Foot contact on soft surfaces reduces TTB both during static and/or dynamic tasks. Further evaluation is needed to clarify the potential pathophysiological implications of this phenomenon. Autism Res 2017, 10: 1547–1557. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 06, 2017   doi: 10.1002/aur.1796   open full text
  • Priority service needs and receipt across the lifespan for individuals with autism spectrum disorder.
    Jonathan K. Y. Lai, Jonathan A. Weiss.
    Autism Research. April 06, 2017
    Individuals with Autism Spectrum Disorder (ASD) have a range of health, community, and social support needs across the lifespan that create age‐specific challenges in navigating service sectors. In this study, we set out to identify the priority needs of individuals with ASD across the lifespan, and the factors that predict receiving priority services. Participants included 3,317 individuals with ASD from a Canada‐wide online caregiver survey, stratified into five age groups (preschool, elementary school age, adolescence, emerging adulthood, adulthood). Priority receipt was calculated as a ratio of current services that corresponded to individualized priority need. Age‐stratified Poisson regression analyses were used to identify the sociodemographic, clinical and systemic predictors of priority receipt. Results indicate that the distribution of priority need varied by age, except for social skills programming, which was a high across all groups. The number of high and moderate priority needs diversified with age. Overall, 30% of individuals had none of their priority needs met and priority receipt decreased with age. Systemic factors were most consistently related to priority receipt across the lifespan. Understanding patterns and correlates of priority needs and use that currently exist in different age groups can inform policies to improve service access. Autism Res 2017. © 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    April 06, 2017   doi: 10.1002/aur.1786   open full text
  • The Childhood Autism Spectrum Test (CAST): Spanish adaptation and validation.
    Paula Morales‐Hidalgo, Joana Roigé‐Castellví, Andreu Vigil‐Colet, Josefa Canals Sans.
    Autism Research. April 06, 2017
    The Childhood Autism Spectrum Test (CAST; Scott, Baron‐Cohen, Bolton & Brayne, 2002) has proved to be a good test for screening autism spectrum disorders (ASD) and social communication problems. This study provides evidence on its psychometric properties, describe its validity for screening and provides data on its discriminative capabilities in a Spanish sample of 4–12 year‐old children from community and clinical settings (N = 1460 and 36, respectively). Factorial and convergent validity is also assessed. The full Spanish version with a cut‐off score of 15 presented a high sensitivity (83.9%) and specificity (92.5%), a positive predictive value (PPV) of .63 and an internal consistency (α) of .826. Some items showed low discriminating power and these results led us to propose a reduced version with 28 items and a cut‐off score of 13, which presented a high sensitivity (85.7%) and specificity (91.16%), a PPV of .61 and an α of .839. Correlations were high between the Spanish full and reduced versions of the CAST, and ADI‐R (Autism Diagnostic Interview Revised) and ADOS‐2 (Autism Diagnostic Observation Schedule, Second Edition). Like previous adaptation studies, a two‐factor structure was found. The data show that the CAST can be a valid and reliable questionnaire for ASD screening in Spanish clinical and community populations. Autism Res 2017, 10: 1491–1498. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 06, 2017   doi: 10.1002/aur.1793   open full text
  • Psychophysiological responses to emotions of others in young children with autism spectrum disorders: Correlates of social functioning.
    Gemma Zantinge, Sophie van Rijn, Lex Stockmann, Hanna Swaab.
    Autism Research. April 06, 2017
    Studying cognitive and affective mechanisms of social behavior could lead to identifying early indicators of derailing social behavior in young children with Autism Spectrum Disorders (ASD). The present study combined sensitive and objective techniques, such as eyetracking and psychophysiology, to provide insight into early neurodevelopmental mechanisms that are more difficult to uncover when relying on behavioral measures. Social attention towards faces and changes in affective arousal were investigated together in 28 young children with ASD (42–75 months) and 45 nonclinical controls (41–81 months). Children were shown a social‐emotional video clip while eyetracking and heart rate were measured. Children with ASD fixated less on key social‐emotional features within the clip as compared to controls, even though both groups attended equally toward the screen. In contrast to the control group, children with ASD did not show an increase or modulation in affective arousal in response to the social‐emotional scenes. Severity of ASD symptoms, specifically social problems, was associated with arousal modulation and social attention within the ASD group. Early ASD symptoms are associated with impairments in fundamental building blocks of social behavior as expressed in a lack in spontaneous social attention and affective arousal. Such sensitive and objective measures of underlying mechanisms might serve as indicators for tailored approaches in treatment and may help in evaluating effectiveness of early interventions aimed at positively influencing social development and related quality of life in individuals with ASD. Autism Res 2017, 10: 1499–1509. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 06, 2017   doi: 10.1002/aur.1794   open full text
  • Latent constructs underlying sensory subtypes in children with autism: A preliminary study.
    Brittany N. Hand, Simon Dennis, Alison E. Lane.
    Autism Research. April 01, 2017
    Recent reports identify sensory subtypes in ASD based on shared patterns of responses to daily sensory stimuli [Ausderau et al., 2014; Lane, Molloy, & Bishop, 2014]. Lane et al. propose that two broad sensory dimensions, sensory reactivity and multisensory integration, best explain the differences between subtypes, however this has yet to be tested. The present study tests this hypothesis by examining the latent constructs underlying Lane's sensory subtypes. Participants for this study were caregivers of children with autism spectrum disorder (ASD) aged 2–12 years. Caregiver responses on the Short Sensory Profile (SSP), used to establish Lane's sensory subtypes, were extracted from two existing datasets (total n = 287). Independent component analyses were conducted to test the fit and interpretability of a two‐construct structure underlying the SSP, and therefore, the sensory subtypes. The first construct was largely comprised of the taste/smell sensitivity domain, which describes hyper‐reactivity to taste and smell stimuli. The second construct had a significant contribution from the low energy/weak domain, which describes behaviors that may be indicative of difficulties with multisensory integration. Findings provide initial support for our hypothesis that sensory reactivity and multisensory integration underlie Lane's sensory subtypes in ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 01, 2017   doi: 10.1002/aur.1787   open full text
  • Infants at‐risk for autism spectrum disorder: Patterns of vocalizations at 14 months.
    Dunia Garrido, Linda R. Watson, Gloria Carballo, Rocio Garcia‐Retamero, Elizabeth R. Crais.
    Autism Research. April 01, 2017
    Differences in the early development of children are crucial for early detection of autism spectrum disorder (ASD). Previous studies have shown large differences between children later diagnosed with ASD and their typically developing peers in the early use of canonical vocalizations (i.e., vocalizations that include well‐formed consonant–vowel syllables) and the use of vocalizations for communicative purposes. In this prospective study, we examined the extent to which infant vocalizations at 14 months would predict Autism Diagnostic Observation Schedule (ADOS) diagnostic symptom groups, that is, Autism, Spectrum, and Non‐ASD, for 82 community‐identified at‐risk infants at 23 months. Thirty‐minute video samples were coded with the intention to categorize and quantify speech (canonical/noncanonical and directed/nondirected) and nonspeech vocalizations (atypical, distress, and pleasure vocalizations). Our results revealed that more canonical directed (OR = 1.039, P = .036), and fewer noncanonical directed (OR=.607, P = .002) and noncanonical nondirected (OR = 1.200, P = .049) vocalizations were associated with a greater likelihood of being in the Non‐ASD group versus the Autism group, with no variables significantly predicting Autism versus Spectrum group membership. Despite some statistically significant findings, models performed poorly in classifying children into correct ASD symptom group at age 23 months based on vocalizations at 14 months. Thus, the utility of infant vocalizations alone for predicting toddler clinical outcomes among infants initially identified at an elevated risk for ASD appears limited; however, considering the structure and function of early vocalizations combined with other early developmental and behavioral features may improve the confidence for clinicians in making an early diagnosis of ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 01, 2017   doi: 10.1002/aur.1788   open full text
  • Autism spectrum disorders and the amplitude of auditory brainstem response wave I.
    Mariline Santos, Cristina Marques, Ana Nóbrega Pinto, Raquel Fernandes, Miguel Bebiano Coutinho, Cecília Almeida e Sousa.
    Autism Research. April 01, 2017
    To determine whether children with autism spectrum disorders (ASDs) have an increased number of wave I abnormal amplitudes in auditory brainstem responses (ABRs) than age‐ and sex‐matched typically developing children. This analytical case–control study compared patients with ASDs between the ages of 2 and 6 years and children who had a language delay not associated with any other pathology. Amplitudes of ABR waves I and V; absolute latencies (ALs) of waves I, III, and V; and interpeak latencies (IPLs) I–III, III–IV, and I–V at 90 dB were compared between ASD patients and normally developing children. The study enrolled 40 children with documented ASDs and 40 age‐ and sex‐matched control subjects. Analyses of the ABR showed that children with ASDs exhibited higher amplitudes of wave 1 than wave V (35%) more frequently than the control group (10%), and this difference between groups reached statistical significance by Chi‐squared analysis. There were no significant differences in ALs and IPLs between ASD children and matched controls. To the best of our knowledge, this is the first case–control study testing the amplitudes of ABR wave I in ASD children. The reported results suggest a potential for the use of ABR recordings in children, not only for the clinical assessment of hearing status, but also for the possibility of using amplitude of ABR wave I as an early marker of ASDs allowing earlier diagnosis and intervention. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1300–1305. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 01, 2017   doi: 10.1002/aur.1771   open full text
  • I tawt i taw a puddy tat: Gestures in canary row narrations by high‐functioning youth with autism spectrum disorder.
    Laura B. Silverman, Inge‐Marie Eigsti, Loisa Bennetto.
    Autism Research. April 01, 2017
    This study examined whether individuals with autism spectrum disorder (ASD) produce co‐speech gestures similarly to typically developing (TD) peers. Participants were 20 youth ages 10–18 years with high‐functioning ASD and 21 TD controls matched on age, gender, verbal IQ, and handedness. Gestures were elicited using a classic narrative‐retelling task, in which participants watched a Tweety and Sylvester cartoon and retold the cartoon to a confederate. Analyses compared gesture rate, type, and viewpoint (character, observer, dual) across groups. Communicative utility of gestures was measured via naïve coder ratings of whether a movement was a gesture, and the clarity of a gesture's meaning. The ASD group produced shorter narratives and fewer total gestures than the TD group. Accounting for narrative length, the ASD group produced fewer gestures per clause than the TD group; however, proportions of gesture types (iconic, deictic, beat, metaphoric, emblems) did not differ. Most notably, the ASD group's gestures were rated as less clearly gestures in terms of timing and well formedness, with lower certainty ratings for gesture meaning. Gesture clarity and gesture meaning scores were related to diagnostic measures of gesture competence in ASD. Findings suggest that although fluent children and adolescents with ASD use the same type of gestures as controls, their gestures are more difficult to understand, which has significant implications for their communicative abilities more broadly. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 01, 2017   doi: 10.1002/aur.1785   open full text
  • Auditory spatial attention to speech and complex non‐speech sounds in children with autism spectrum disorder.
    Laura N. Soskey, Paul D. Allen, Loisa Bennetto.
    Autism Research. April 01, 2017
    One of the earliest observable impairments in autism spectrum disorder (ASD) is a failure to orient to speech and other social stimuli. Auditory spatial attention, a key component of orienting to sounds in the environment, has been shown to be impaired in adults with ASD. Additionally, specific deficits in orienting to social sounds could be related to increased acoustic complexity of speech. We aimed to characterize auditory spatial attention in children with ASD and neurotypical controls, and to determine the effect of auditory stimulus complexity on spatial attention. In a spatial attention task, target and distractor sounds were played randomly in rapid succession from speakers in a free‐field array. Participants attended to a central or peripheral location, and were instructed to respond to target sounds at the attended location while ignoring nearby sounds. Stimulus‐specific blocks evaluated spatial attention for simple non‐speech tones, speech sounds (vowels), and complex non‐speech sounds matched to vowels on key acoustic properties. Children with ASD had significantly more diffuse auditory spatial attention than neurotypical children when attending front, indicated by increased responding to sounds at adjacent non‐target locations. No significant differences in spatial attention emerged based on stimulus complexity. Additionally, in the ASD group, more diffuse spatial attention was associated with more severe ASD symptoms but not with general inattention symptoms. Spatial attention deficits have important implications for understanding social orienting deficits and atypical attentional processes that contribute to core deficits of ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    April 01, 2017   doi: 10.1002/aur.1790   open full text
  • Perception of odors and tastes in autism spectrum disorders: A systematic review of assessments.
    Mohamed A. Boudjarane, Marine Grandgeorge, Rémi Marianowski, Laurent Misery, Éric Lemonnier.
    Autism Research. March 30, 2017
    Olfaction and gustation are major sensory functions implied in processing environmental stimuli. Some evidences suggest that loss of olfactory function is an early biomarker for neurodegenerative disorders and atypical processing of odor and taste stimuli is present in several neurodevelopmental disorders, notably in Autism Spectrum Disorders (ASD). In this paper, we conducted a systematic review investigating the assessments of olfaction and gustation with psychophysics methods in individuals with ASD. Pubmed, PMC and Sciencedirect were scrutinized for relevant literature published from 1970 to 2015. In this review, fourteen papers met our inclusion criteria. They were analyzed critically in order to evaluate the occurrence of olfactory and gustatory dysfunction in ASD, as well as to report the methods used to assess olfaction and gustation in such conditions. Regarding to these two senses, the overall number of studies is low. Most of studies show significant difference regarding to odor or taste identification but not for detection threshold. Overall, odor rating through pleasantness, intensity and familiarity do not differ significantly between control and individuals with ASD. The current evidences can suggest the presence of olfactory and gustatory dysfunction in ASD. Therefore, our analysis show a heterogeneity of findings. This is due to several methodological limitations such as the tools used or population studied. Understanding these disorders could help to shed light on other atypical behavior in this population such as feeding or social behavior. Autism Res 2017, 0: 000–000. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 30, 2017   doi: 10.1002/aur.1760   open full text
  • Acquisition of voice onset time in toddlers at high and low risk for autism spectrum disorder.
    Karen Chenausky, Helen Tager‐Flusberg.
    Autism Research. March 24, 2017
    Although language delay is common in autism spectrum disorder (ASD), research is equivocal on whether speech development is affected. We used acoustic methods to investigate the existence of sub‐perceptual differences in the speech of toddlers who developed ASD. Development of the distinction between b and p was prospectively tracked in 22 toddlers at low risk for ASD (LRC), 22 at high risk for ASD without ASD (HRA−), and 11 at high risk for ASD who were diagnosed with ASD at 36 months (HRA+). Voice onset time (VOT), the main acoustic difference between b and p, was measured from spontaneously produced words at 18, 24, and 36 months. Number of words, number of tokens (instances) of syllable‐initial b and p produced, error rates, language scores, and motor ability were also assessed. All groups' mean language scores were within the average range or slightly higher. No between‐group differences were found in number of words, b's, p's, or errors produced; or in mean or standard deviation of VOT. Binary logistic regression showed that only diagnostic status, not language score, motor ability, number of words, number of b's and p's, or number of errors significantly predicted whether a toddler produced acoustically distinct b and p populations at 36 months. HRA+ toddlers were significantly less likely to produce acoustically distinct b's and p's at 36 months, which may indicate that the HRA+ group may be using different strategies to produce this distinction. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1269–1279. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 24, 2017   doi: 10.1002/aur.1775   open full text
  • Are schizophrenia, autistic, and obsessive spectrum disorders dissociable on the basis of neuroimaging morphological findings?: A voxel‐based meta‐analysis.
    Franco Cauda, Tommaso Costa, Andrea Nani, Luciano Fava, Sara Palermo, Francesca Bianco, Sergio Duca, Karina Tatu, Roberto Keller.
    Autism Research. March 24, 2017
    Schizophrenia spectrum disorder (SCZD), autism spectrum disorder (ASD), and obsessive‐compulsive spectrum disorder (OCSD) are considered as three separate psychiatric conditions with, supposedly, different brain alterations patterns. From a neuroimaging perspective, this meta‐analytic study aimed to address whether this nosographical differentiation is actually supported by different brain patterns of gray matter (GM) or white matter (WM) morphological alterations. We explored two possibilities: (a) to find out whether GM alterations are specific for SCZD, ASD, and OCSD; and (b) to associate the identified brain alteration patterns with cognitive dysfunctions by means of an analysis of lesion decoding. Our analysis reveals that these psychiatric spectra do not present clear distinctive patterns of alterations; rather, they all tend to be distributed in two alteration clusters. Cluster 1, which is more specific for SCZD, includes the anterior insular, anterior cingulate cortex, ventromedial prefrontal cortex, and frontopolar areas, which are parts of the cognitive control system. Cluster 2, which is more specific for OCSD, presents occipital, temporal, and parietal alteration patterns with the involvement of sensorimotor, premotor, visual, and lingual areas, thus forming a network that is more associated with the auditory‐visual, auditory, premotor visual somatic functions. In turn, ASD appears to be uniformly distributed in the two clusters. The three spectra share a significant set of alterations. Our new approach promises to provide insight into the understanding of psychiatric conditions under the aspect of a common neurobiological substrate, possibly related to neuroinflammation during brain development. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 24, 2017   doi: 10.1002/aur.1759   open full text
  • Multisensory speech perception in autism spectrum disorder: From phoneme to whole‐word perception.
    Ryan A. Stevenson, Sarah H. Baum, Magali Segers, Susanne Ferber, Morgan D. Barense, Mark T. Wallace.
    Autism Research. March 24, 2017
    Speech perception in noisy environments is boosted when a listener can see the speaker's mouth and integrate the auditory and visual speech information. Autistic children have a diminished capacity to integrate sensory information across modalities, which contributes to core symptoms of autism, such as impairments in social communication. We investigated the abilities of autistic and typically‐developing (TD) children to integrate auditory and visual speech stimuli in various signal‐to‐noise ratios (SNR). Measurements of both whole‐word and phoneme recognition were recorded. At the level of whole‐word recognition, autistic children exhibited reduced performance in both the auditory and audiovisual modalities. Importantly, autistic children showed reduced behavioral benefit from multisensory integration with whole‐word recognition, specifically at low SNRs. At the level of phoneme recognition, autistic children exhibited reduced performance relative to their TD peers in auditory, visual, and audiovisual modalities. However, and in contrast to their performance at the level of whole‐word recognition, both autistic and TD children showed benefits from multisensory integration for phoneme recognition. In accordance with the principle of inverse effectiveness, both groups exhibited greater benefit at low SNRs relative to high SNRs. Thus, while autistic children showed typical multisensory benefits during phoneme recognition, these benefits did not translate to typical multisensory benefit of whole‐word recognition in noisy environments. We hypothesize that sensory impairments in autistic children raise the SNR threshold needed to extract meaningful information from a given sensory input, resulting in subsequent failure to exhibit behavioral benefits from additional sensory information at the level of whole‐word recognition. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1280–1290. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 24, 2017   doi: 10.1002/aur.1776   open full text
  • Parental relationship satisfaction in families of children with autism spectrum disorder (ASD): A multilevel analysis.
    Emma Langley, Vasiliki Totsika, Richard P. Hastings.
    Autism Research. March 24, 2017
    Caring for a child with Autism Spectrum Disorder (ASD) has been linked to a range of negative outcomes for parents but less is known about the putative impact upon the parental couple relationship. The relationship satisfaction of parents of children with ASD was investigated using multilevel modeling. Mothers and fathers (146 couples) reported on their relationship satisfaction, their own well‐being, and the behavior problems of the child with ASD and a sibling. Results indicated that mothers and fathers reported similar levels of relationship satisfaction and it was significantly and negatively associated with parental depression and the behavior problems of the child with ASD. Relationship satisfaction was unrelated to the behavior problems of a sibling, the number of children in the household, and family socioeconomic position (SEP). Further longitudinal research that captures a broader range of variables is required to build a theoretical understanding of relationship satisfaction in families of children with ASD. Current evidence suggests that early intervention routes targeting either child behavior problems, parental mental health, or the couple relationship have the potential to benefit inter‐connected subsystems within the broader family system. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1259–1268. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 24, 2017   doi: 10.1002/aur.1773   open full text
  • Identification of likely associations between cerebral folate deficiency and complex genetic‐ and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach.
    Daniel Krsička, Jan Geryk, Markéta Vlčková, Markéta Havlovicová, Milan Macek, Radka Pourová.
    Autism Research. March 24, 2017
    Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, the exact role of folate metabolism in the pathogenesis of ASD, identification of underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. The aim of our study was to develop and test a novel, unbiased, bioinformatics approach in order to identify links between ASD and disturbed cerebral metabolism by focusing on abnormal folate metabolism, which could foster patient stratification and novel therapeutic interventions. An unbiased, automatable, computational workflow interaction model was developed using available data from public databases. The interaction network model of ASD‐associated genes with known cerebral expression and function (SFARI) and metabolic networks (MetScape), including connections to known metabolic substrates, metabolites and cofactors involving folates, was established. Intersection of bioinformatically created networks resulted in a limited amount of interaction modules pointing to common disturbed metabolic pathways, linking ASD to CFD. Two independent interaction modules (comprising three pathways) covering enzymes encoded by ASD‐related genes and folate cofactors utilizing enzymes were generated. Module 1 suggested possible interference of CFD with serine and lysine metabolism, while module 2 identified correlations with purine metabolism and inosine monophosphate production. Since our approach was primarily conceived as a proof of principle, further amendments of the presented initial model are necessary to obtain additional actionable outcomes. Our modelling strategy identified not only previously known interactions supported by evidence‐based analyses, but also novel plausible interactions, which could be validated in subsequent functional and/or clinical studies. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 24, 2017   doi: 10.1002/aur.1780   open full text
  • Don't touch me! autistic traits modulate early and late ERP components during visual perception of social touch.
    Leehe Peled‐Avron, Simone G. Shamay‐Tsoory.
    Autism Research. March 24, 2017
    Although individuals with autism spectrum disorder (ASD) have impaired responses to interpersonal touch, the underlying neural correlates remain largely unknown. Here, we examined the neural correlates that underlie interpersonal touch perception in individuals with either high or low autistic traits. Fifty‐three participants were classified as having either high or low autistic traits based on their performance on the autism quotient (AQ) questionnaire. We hypothesized that individuals with high AQ scores would have relatively high touch hypervigilance, reflected as earlier P1 and stronger late positive potential (LPP) responses, two components of event‐related potentials that serve as electrophysiological markers of anxiety bias. We recorded each participant's electroencephalography activity during presentation of images depicting human touch, object touch, and non‐touch control images. Consistent with our hypothesis, AQ scores were positively correlated with social touch aversion. Moreover, participants with high AQ scores had earlier P1 and stronger LPP responses when presented with human touch compared to the control images. Importantly, a regression model revealed that earlier P1 and larger LPP amplitude measured during social touch observation can accurately predict higher autistic trait levels. Taken together, these findings indicate that individuals with high levels of autistic traits may have a hypervigilant response to observed social touch. Autism Res 2017, 0: 000–000. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 24, 2017   doi: 10.1002/aur.1762   open full text
  • Response to changing contingencies in infants at high and low risk for autism spectrum disorder.
    Jessie B. Northrup, Klaus Libertus, Jana M. Iverson.
    Autism Research. March 16, 2017
    One recently proposed theory of autism spectrum disorder (ASD) hypothesizes that individuals with the disorder may have difficulty using prior experiences to predict future events [Hellendoorn et al., 2015; Northrup, 2016; Sinha et al., 2014]. To date, this theory has not been tested in infancy. The current study analyzed how young infants at heightened (HR; older sibling with ASD) vs. low risk (LR; no first degree relatives with ASD) for ASD responded to changing contingencies when interacting with two visually identical rattles—one that produced sounds during shaking (Sound), and one that did not (Silent). Infants were given the rattles in a Sound‐Silent‐Sound order at 6 and 10 months, and shaking behavior was coded. Results indicated that LR and HR infants (regardless of ASD diagnosis) did not differ from each other in shaking behavior at 6 months. However, by 10 months, LR infants demonstrated high initial shaking with all three rattles, indicating expectations for rattle affordances, while HR infants did not. Significantly, HR infants, and particularly those with an eventual ASD diagnosis, did not demonstrate an “extinction burst”—or high level of shaking—in the first 10 sec with the “silent” rattle, indicating that they may have difficulty generalizing learning from one interaction to the next. Further, individual differences in the strength of this “extinction burst” predicted cognitive development in toddlerhood among HR infants. Difficulty forming expectations for new interactions based on previous experiences could impact learning and behavior in a number of domains. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1239–1248. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 16, 2017   doi: 10.1002/aur.1770   open full text
  • Age‐specific autistic‐like behaviors in heterozygous Fmr1‐KO female mice.
    Manon Gauducheau, Valerie Lemaire‐Mayo, Francesca R. D'Amato, Diego Oddi, Wim E. Crusio, Susanna Pietropaolo.
    Autism Research. March 16, 2017
    Fragile X syndrome (FXS) is a major developmental disorder and the most frequent monogenic cause of autism. Surprisingly, most existing studies on the Fmr1‐KO mouse model for FXS have focused on males, although FX women, who are mostly heterozygous for the Fmr1 mutation, are known to exhibit several behavioral deficits, including autistic‐like features. Furthermore, most animal research has been carried out on adults only; so that little is known about the age progression of the behavioral phenotype of Fmr1 mutants, which is a crucial issue to optimize the impact of therapeutic interventions. Here, we performed an extensive analysis of autistic‐like social behaviors in heterozygous (HET) Fmr1‐KO females and their WT littermates at different ages. No behavioral difference between HET and WT mice was observed at infancy, but some abnormalities in social interaction and communication were first detected at juvenile age. At adulthood some of these alterations disappeared, but avoidance of social novelty appeared, together with other FXS‐relevant behavioral deficits, such as hyperactivity and reduced contextual fear response. Our data provide for the first time evidence for the presence of autistic‐relevant behavioral abnormalities in Fmr1‐HET female mice, demonstrating the utility of this mouse line to model autistic‐like behaviors in both sexes. These results also highlight the importance of taking into account age differences when using the Fmr1‐KO mouse model, suggesting that the early post‐natal phases are the most promising target for preventive interventions and the adult age is the most appropriate to investigate the behavioral impact of potential therapies. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 16, 2017   doi: 10.1002/aur.1743   open full text
  • Shorter sleep duration is associated with social impairment and comorbidities in ASD.
    Olivia J. Veatch, James S. Sutcliffe, Zachary E. Warren, Brendan T. Keenan, Melissa H. Potter, Beth A. Malow.
    Autism Research. March 16, 2017
    Sleep disturbance, particularly insomnia, is common in children with autism spectrum disorders (ASD). Furthermore, disturbed sleep affects core symptoms and other related comorbidities. Understanding the causes and consequences of sleep disturbances in children with ASD is an important step toward mitigating these symptoms. To better understand the connection between sleep duration and ASD severity, we analyzed ASD‐related symptoms using the Autism Diagnostic Interview‐Revised (ADI‐R), Autism Diagnostic Observation Schedule (ADOS), IQ scores, and parent reports of the average amount of time slept per night that were available in the medical histories of 2,714 children with ASD in the Simons Simplex Collection (SSC). The mean (SD) sleep duration was 555 minutes. Sleep duration and severity of core ASD symptoms were negatively correlated, and sleep duration and IQ scores were positively correlated. Regression results indicated that more severe social impairment, primarily a failure to develop peer relationships, is the core symptom most strongly associated with short sleep duration. Furthermore, increased severity for numerous maladaptive behaviors assessed on the Child Behavior Checklist, as well as reports of attention deficit disorder, depressive disorder, and obsessive compulsive disorder were associated with short sleep duration. Severity scores for social/communication impairment and restricted and repetitive behaviors (RRB) were increased, and IQ scores were decreased, for children reported to sleep ≤420 minutes per night (lower 5th percentile) compared to children sleeping ≥660 minutes (upper 95th percentile). Our results indicate that reduced amounts of sleep are related to more severe symptoms in children with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1221–1238. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 16, 2017   doi: 10.1002/aur.1765   open full text
  • Neural correlates of language variability in preschool‐aged boys with autism spectrum disorder.
    Letitia R. Naigles, Ryan Johnson, Ann Mastergeorge, Sally Ozonoff, Sally J. Rogers, David G. Amaral, Christine Wu Nordahl.
    Autism Research. March 16, 2017
    Children with autism vary widely in their language abilities, yet the neural correlates of this language variability remain unclear, especially early in development. Diffusion tensor imaging (DTI) was used to examine diffusivity measures along the length of 18 major fiber tracts in 104 preschool‐aged boys with autism spectrum disorder (ASD). The boys were assigned to subgroups according to their level of language development (Low: no/low language, Middle: small vocabulary, High: large vocabulary and grammar), based on their raw scores on the expressive language (EL) and receptive language (RL) sections of the Mullen Scales of Early Learning (MSEL). Results indicate that the subgroups differed in fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) along the inferior longitudinal fasciculus (ILF) in both hemispheres. Moreover, FA correlated significantly with Mullen EL and RL raw scores, but not ADOS severity score, along the left and right ILF. Subgroups also differed in MD (but not FA) along the left superior longitudinal fasiculus and left corticospinal tract, but these differences were not correlated with language scores. These findings suggest that white matter microstructure in the left and right ILF varies in relation to lexical development in young males with ASD. The findings also support the use of raw scores on language‐relevant standardized tests for assessing early language‐brain relationships. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 16, 2017   doi: 10.1002/aur.1756   open full text
  • Binocular rivalry in children on the autism spectrum.
    Themelis Karaminis, Claudia Lunghi, Louise Neil, David Burr, Elizabeth Pellicano.
    Autism Research. March 16, 2017
    When different images are presented to the eyes, the brain is faced with ambiguity, causing perceptual bistability: visual perception continuously alternates between the monocular images, a phenomenon called binocular rivalry. Many models of rivalry suggest that its temporal dynamics depend on mutual inhibition among neurons representing competing images. These models predict that rivalry should be different in autism, which has been proposed to present an atypical ratio of excitation and inhibition [the E/I imbalance hypothesis; Rubenstein & Merzenich, 2003]. In line with this prediction, some recent studies have provided evidence for atypical binocular rivalry dynamics in autistic adults. In this study, we examined if these findings generalize to autistic children. We developed a child‐friendly binocular rivalry paradigm, which included two types of stimuli, low‐ and high‐complexity, and compared rivalry dynamics in groups of autistic and age‐ and intellectual ability‐matched typical children. Unexpectedly, the two groups of children presented the same number of perceptual transitions and the same mean phase durations (times perceiving one of the two stimuli). Yet autistic children reported mixed percepts for a shorter proportion of time (a difference which was in the opposite direction to previous adult studies), while elevated autistic symptomatology was associated with shorter mixed perception periods. Rivalry in the two groups was affected similarly by stimulus type, and consistent with previous findings. Our results suggest that rivalry dynamics are differentially affected in adults and developing autistic children and could be accounted for by hierarchical models of binocular rivalry, including both inhibition and top‐down influences. Autism Res 2017. ©2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    March 16, 2017   doi: 10.1002/aur.1749   open full text
  • A clinician‐administered observation and corresponding caregiver interview capturing DSM‐5 sensory reactivity symptoms in children with ASD.
    Paige M. Siper, Alexander Kolevzon, A. Ting Wang, Joseph D. Buxbaum, Teresa Tavassoli.
    Autism Research. March 11, 2017
    Sensory reactivity, including hyperreactivity, hyporeactivity, and sensation seeking, is a new criterion for autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5). However, there is no consensus on how to reliably measure sensory reactivity, particularly in minimally verbal individuals. The current study is an initial validation of the Sensory Assessment for Neurodevelopmental Disorders (SAND), a novel clinician‐administered observation and corresponding caregiver interview that captures sensory symptoms based on DSM‐5 criteria for ASD. DSM‐5 criteria of sensory hyperreactivity, hyporeactivity, and seeking behaviors are measured across visual, auditory, and tactile domains. Children with ASD showed significantly more sensory reactivity symptoms compared to typically developing (TD) children across sensory domains (visual, tactile, and auditory) and within each sensory subtype (hyperreactivity, hyporeactivity, and seeking). Psychometric properties including internal consistency, inter‐rater reliability, test‐retest reliability, and convergent validity were all strong. The SAND provides a novel method to characterize sensory reactivity symptoms based on DSM‐5 criteria for ASD. This is the first known sensory assessment that combines a clinician‐administered observation and caregiver interview to optimally capture sensory phenotypes characteristic of individuals with neurodevelopmental disorders. The SAND offers a beneficial new tool for both research and clinical purposes and has the potential to meaningfully enhance gold‐standard assessment of ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 11, 2017   doi: 10.1002/aur.1750   open full text
  • The urinary 1H‐NMR metabolomics profile of an italian autistic children population and their unaffected siblings.
    Milena Lussu, Antonio Noto, Alice Masili, Andrea C. Rinaldi, Angelica Dessì, Maria De Angelis, Andrea De Giacomo, Vassilios Fanos, Luigi Atzori, Ruggiero Francavilla.
    Autism Research. March 11, 2017
    Autism spectrum disorders (ASD) make a dishomogeneous group of psychiatric diseases having either genetic and environmental components, including changes of the microbiota. The rate of diagnosis, based on a series of psychological tests and observed behavior, dramatically increased in the past few decades. Currently, no biological markers are available and the pathogenesis is not defined. The purpose of this study was to evaluate the potential use of 1H‐NMR metabolomics to analyze the global biochemical signature of ASD patients (n = 21) and controls (n = 21), these being siblings of autistic patients. A multivariate model has been used to extrapolate the variables of importance. The discriminating urinary metabolites were identified; in particular, significantly increased levels of hippurate, glycine, creatine, tryptophan, and d‐threitol and decreased concentrations of glutamate, creatinine, lactate, valine, betaine, and taurine were observed in ASD patients. Based on the identified discriminant metabolites, the attention was focused on two possible mechanisms that could be involved in ASD: oxidative stress conditions and gut microflora modifications. In conclusion, nuclear magnetic resonance‐based metabolomics analysis of the urine seems to have the potential for the identification of a metabolic fingerprint of ASD phenotypes and appears to be suitable for further investigation of the disease mechanisms. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 11, 2017   doi: 10.1002/aur.1748   open full text
  • A new test of advanced theory of mind: The “Strange Stories Film Task” captures social processing differences in adults with autism spectrum disorders.
    Kim Murray, Kate Johnston, Helen Cunnane, Charlotte Kerr, Debbie Spain, Nicola Gillan, Neil Hammond, Declan Murphy, Francesca Happé.
    Autism Research. March 11, 2017
    Real‐life social processing abilities of adults with autism spectrum disorders (ASD) can be hard to capture in lab‐based experimental tasks. A novel measure of social cognition, the “Strange Stories Film task’ (SSFt), was designed to overcome limitations of available measures in the field. Brief films were made based on the scenarios from the Strange Stories task (Happé) and designed to capture the subtle social‐cognitive difficulties observed in ASD adults. Twenty neurotypical adults were recruited to pilot the new measure. A final test set was produced and administered to a group of 20 adults with ASD and 20 matched controls, alongside established social cognition tasks and questionnaire measures of empathy, alexithymia and ASD traits. The SSFt was more effective than existing measures at differentiating the ASD group from the control group. In the ASD group, the SSFt was associated with the Strange Stories task. The SSFt is a potentially useful tool to identify social cognitive dis/abilities in ASD, with preliminary evidence of adequate convergent validity. Future research directions are discussed. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 11, 2017   doi: 10.1002/aur.1744   open full text
  • Variations of stereotypies in individuals with Rett syndrome: A nationwide cross‐sectional study in Taiwan.
    Lee Chin Wong, Pi‐Lien Hung, Tz‐Yun Jan, Wang‐Tso Lee,.
    Autism Research. March 08, 2017
    Individuals with Rett syndrome (RTT) can have variable manifestations of stereotypies. In this nation‐wide cross‐sectional study, we recruited all individuals with RTT in Taiwan diagnosed as RTT by neurologists based on genetic findings and diagnostic criteria. The data were collected using questionnaire. A total 43 cases of typical RTT and 15 cases of atypical RTT, aged from 2.1 to 40.1 years, were enrolled. They included 3 (5.2%) in stage II, 42 (72.4%) in stage III, and 13 (22.4%) in stage IV. All individuals presented with at least one stereotypy. Individuals with atypical RTT had more varied stereotypies (mean: 14 ± 6) compared to those with typical RTT (mean: 9 ± 5) (P = 0.003). Flapping (73.3%) and wringing (58.1%) were the most common hand stereotypies in atypical and typical RTT, respectively. Compared with typical RTT, hair pulling, bruxism, retropulsion, and protrusion of lips were more common in atypical RTT (P = 0.003, P = 0.006, P = 0.003 and <0.001, respectively). The number of stereotypies did not differ among different stages, clinical severities, and hand functions. Although there were no age‐related changes in stereotypies in atypical RTT, flapping (P = 0.012), clapping (P = 0.044), and mouthing with single hand (P = 0.009) were significantly more prevalent in individuals aged <10 years with typical RTT, and they decreased after 10 years. In conclusion, our study showed that the stereotypical movements varied in typical and atypical RTT, implying the heterogeneous nature of the disease and the pathogenic mechanisms of RTT with atypical features. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1204–1214. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 08, 2017   doi: 10.1002/aur.1774   open full text
  • A pilot study of serotonergic modulation after long‐term administration of oxytocin in autism spectrum disorder.
    Tetsu Hirosawa, Mitsuru Kikuchi, Yasuomi Ouchi, Tetsuya Takahashi, Yuko Yoshimura, Hirotaka Kosaka, Naoki Furutani, Hirotoshi Hiraishi, Mina Fukai, Masamichi Yokokura, Etsuji Yoshikawa, Tomoyasu Bunai, Yoshio Minabe.
    Autism Research. March 07, 2017
    Oxytocin (OT) and the serotonergic system putatively play important roles in autism spectrum disorder (ASD) etiology and symptoms, but no direct neurobiological evidence exists for long‐term OT administration effects on the brain's serotonergic system. This pilot study examined 10 male participants with ASD who were administered OT intranasally for 8–10 weeks in an open‐label, single‐arm, nonrandomized, and uncontrolled manner. Positron emission tomography (PET) with a radiotracer (11C)−3‐amino‐4‐(2‐[(dimethylamino)methyl]phenylthio)benzonitrile (11C‐DASB) was used before and after OT treatment. The binding potential of serotonin transporter (11C‐DASB BPND) was then estimated. The main outcome measures were changes in 11C‐DASB BPND and their correlation with changes in symptoms. ASD participants showed significantly elevated 11C‐DASB BPND in the left inferior frontal gyrus extending to the left middle frontal gyrus. No significant correlation was found between the change in any clinical symptom and the change in 11C‐DASB BPND. This report of a pilot study is the first describing long‐term effects of OT on the brain's serotonin system in ASD. Additional randomized controlled studies must be conducted to confirm whether activation of the serotonergic system contributes to the prosocial effect of OT in people with ASD. Autism Res 2017, 10: 821–828. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 07, 2017   doi: 10.1002/aur.1761   open full text
  • Autism spectrum disorder in sub‐saharan africa: A comprehensive scoping review.
    Lauren Franz, Nola Chambers, Megan von Isenburg, Petrus J. de Vries.
    Autism Research. March 07, 2017
    Autism spectrum disorder (ASD) is recognized as a global public health concern, yet almost everything we know about ASD comes from high‐income countries. Here we performed a scoping review of all research on ASD ever published in sub‐Saharan Africa (SSA) in order to identify ASD knowledge gaps in this part of the world. Fifty‐three publications met inclusion criteria. Themes included the phenotype, genetics and risk factors for ASD in SSA, screening and diagnosis, professional knowledge, interventions for ASD, parental perceptions, and social‐cognitive neuroscience. No epidemiological, early intervention, school‐based or adult studies were identified. For each identified theme, we aimed to summarize results and make recommendations to fill the knowledge gaps. The quality of study methodologies was generally not high. Few studies used standardized diagnostic instruments, and intervention studies were typically small‐scale. Overall, findings suggest a substantial need for large‐scale clinical, training, and research programmes to improve the lives of people who live with ASD in SSA. However, SSA also has the potential to make unique and globally‐significant contributions to the etiology and treatments of ASD through implementation, interventional, and comparative genomic science. Autism Res 2017, 10: 723–749. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 07, 2017   doi: 10.1002/aur.1766   open full text
  • Aggressive behaviors and treatable risk factors of preschool children with autism spectrum disorder.
    Chen Chen, Yi‐Dong Shen, Guang‐Lei Xun, Wei‐Xiong Cai, Li‐Juan Shi, Lu Xiao, Ren‐Rong Wu, Jing‐Ping Zhao, Jian‐Jun Ou.
    Autism Research. March 07, 2017
    Aggressive behaviors of children with autism spectrum disorder (ASD) are common. We conducted this study to describe the aggressive mode of preschool children with ASD and examine the associations between specific aggressive behaviors and two treatable factors: sleep problems and attention deficit hyperactivity disorder (ADHD) symptoms. In total, 577 typically developing (TD) children and 490 children with ASD were investigated in this study. The Institute for Basic Research – Modified Overt Aggression Scale (IBR‐MOAS) was used to assess aggressive behaviors. Children's social impairments, sleep problems and ADHD symptoms were also measured with specific scales. The total IBR‐MOAS score was significantly higher (worse) in the TD group [4.47 (5.36)] than in the ASD group [3.47 (5.63), P = 0.004]. The aggressive modes differed between groups: when compared with each other, the TD group received higher scores on Verbal and Physical Aggression Toward Others (all P < 0.01), while the ASD group had higher scores on Physical Aggression Against Self (P = 0.006). The linear regression model demonstrated that the aggressive behaviors of children with ASD were significantly associated with two treatable factors: sleep problems and ADHD symptoms. These findings have substantial clinical implications: treatment of these two risk factors may be helpful in managing aggressive behavior in children with ASD. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 07, 2017   doi: 10.1002/aur.1751   open full text
  • Social communication in children with autism spectrum disorder (asd): Correlation between DSM‐5 and autism classification system of functioning—social communication (ACSF:SC).
    Francesco Craig, Isabella Fanizza, Luigi Russo, Elisabetta Lucarelli, Alessandro Lorenzo, Maria Grazia Pasca, Antonio Trabacca.
    Autism Research. March 07, 2017
    The aim of this study was to classify children with Autism Spectrum Disorder (ASD) according to Autism Classification System of Functioning: Social Communication (ACSF:SC) criteria, in order to investigate the association between social communication ability, ASD severity, adaptive functioning, cognitive abilities and psychoeducational profile. The severity of social communication impairment was specified through Diagnostic and Statistical Manual of Mental Disorders‐5th edition (DSM‐5) and ACSF:SC tool. The ADOS‐2, Vineland‐II and PEP‐3 were administered to all participants. We found a positive correlation between DSM‐5 levels and ACSF:SC‐Typical Performance (r = 0.35; P = 0.007) and ACSF:SC‐Capacity (r = 0.31; P = 0.01) levels. Children included in the five levels of ACSF:SC (Typical Performance and Capacity) showed statistically significant differences in ADOS‐2 (Social Affect), Vineland‐II (Communication and Socialization), and PEP‐3 (Communication, motor skills, maladaptive behavior) scores. The results of this study indicate that ACSF:SC provide a better understanding of functional profile of children with ASD based on the social communication abilities. Children with greater severity of social communication showed more difficulty in adaptive behavior and psychoeducational profiles. In conclusion, the ACSF:SC could help clinicians and therapists not only to understand the strength and weakness of preschool children with ASD but also to devise specific treatment in order to promote their social integration. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1249–1258. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 07, 2017   doi: 10.1002/aur.1772   open full text
  • Ensemble perception in autism spectrum disorder: Member‐identification versus mean‐discrimination.
    Ruth Van der Hallen, Lisa Lemmens, Jean Steyaert, Ilse Noens, Johan Wagemans.
    Autism Research. March 07, 2017
    To efficiently represent the outside world our brain compresses sets of similar items into a summarized representation, a phenomenon known as ensemble perception. While most studies on ensemble perception investigate this perceptual mechanism in typically developing (TD) adults, more recently, researchers studying perceptual organization in individuals with autism spectrum disorder (ASD) have turned their attention toward ensemble perception. The current study is the first to investigate the use of ensemble perception for size in children with and without ASD (N = 42, 8–16 years). We administered a pair of tasks pioneered by Ariely [2001] evaluating both member‐identification and mean‐discrimination. In addition, we varied the distribution types of our sets to allow a more detailed evaluation of task performance. Results show that, overall, both groups performed similarly in the member‐identification task, a test of “local perception,” and similarly in the mean identification task, a test of “gist perception.” However, in both tasks performance of the TD group was affected more strongly by the degree of stimulus variability in the set, than performance of the ASD group. These findings indicate that both TD children and children with ASD use ensemble statistics to represent a set of similar items, illustrating the fundamental nature of ensemble coding in visual perception. Differences in sensitivity to stimulus variability between both groups are discussed in relation to recent theories of information processing in ASD (e.g., increased sampling, decreased priors, increased precision). Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1291–1299. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 07, 2017   doi: 10.1002/aur.1767   open full text
  • Perceived social support in adults with autism spectrum disorder and attention‐deficit/hyperactivity disorder.
    Sonia Alvarez‐Fernandez, Hallie R. Brown, Yihong Zhao, Jessica A. Raithel, Somer L. Bishop, Sarah B. Kern, Catherine Lord, Eva Petkova, Adriana Di Martino.
    Autism Research. March 03, 2017
    Perceived social support (PSS) has been related to physical and mental well‐being in typically developing individuals, but systematic characterizations of PSS in autism spectrum disorder (ASD) are limited. We compared self‐report ratings of the multidimensional scale of PSS (MSPSS) among age‐ and IQ‐matched groups of adults (18–58 years) with cognitively high‐functioning ASD (N = 41), or attention‐deficit/hyperactivity disorder (ADHD; N = 69), and neurotypical controls (NC; N = 69). Accompanying group comparisons, we used machine learning random forest (RF) analyses to explore predictors among a range of psychopathological and socio‐emotional variables. Relative to both ADHD and NC, adults with ASD showed lower MSPSS ratings, specifically for the friends subscale (MSPSS‐f). Across ASD and ADHD, interindividual differences in autism severity, affective empathy, symptoms of anxiety related to social interactions, hyperactivity/impulsivity, and somatization best predicted MSPSS‐f. These relationships did not differ between clinical groups. While group comparisons demonstrated greater impairment in individuals with ASD, analyzing individuals' characteristics revealed cross‐diagnoses similarities in regard to their MSPSS‐f relationships. This is consistent with the Research Domain Criteria framework, supporting a trans‐diagnostic approach as on the path toward “precision medicine.” Autism Res 2017, 10: 866–877. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 03, 2017   doi: 10.1002/aur.1735   open full text
  • Assessment of Autistic Traits in Children Aged 2 to 4½ Years With the Preschool Version of the Social Responsiveness Scale (SRS‐P): Findings from Japan.
    Andrew Stickley, Yoshiyuki Tachibana, Keiji Hashimoto, Hideyuki Haraguchi, Atsuko Miyake, Seiichi Morokuma, Hiroshi Nitta, Masako Oda, Yukihiro Ohya, Ayako Senju, Hidetoshi Takahashi, Takanori Yamagata, Yoko Kamio.
    Autism Research. March 03, 2017
    The recent development and use of autism measures for the general population has led to a growing body of evidence which suggests that autistic traits are distributed along a continuum. However, as most existing autism measures were designed for use in children older than age 4, to date, little is known about the autistic continuum in children younger than age 4. As autistic symptoms are evident in the first few years, to address this research gap, the current study tested the preschool version of the Social Responsiveness Scale (SRS‐P) in children aged 2 to 4½ years in clinical (N = 74, average age 40 months, 26–51 months) and community settings (N = 357, average age 39 months, 25–50 months) in Japan. Using information obtained from different raters (mothers, other caregivers, and teachers) it was found that the scale demonstrated a good degree of internal consistency, inter‐rater reliability and test‐retest reliability, and a satisfactory degree of convergent validity for the clinical sample when compared with scores from diagnostic “gold standard” autism measures. Receiver operating characteristic analyses and the group comparisons also showed that the SRS‐P total score discriminated well between children with autism spectrum disorder (ASD) and those without ASD. Importantly, this scale could identify autistic symptoms or traits distributed continually across the child population at this age irrespective of the presence of an ASD diagnosis. These findings suggest that the SRS‐P might be a sensitive instrument for case identification including subthreshold ASD, as well as a potentially useful research tool for exploring ASD endophenotypes. Autism Res 2017, 10: 852–865. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    March 03, 2017   doi: 10.1002/aur.1742   open full text
  • Participation in recreational activities buffers the impact of perceived stress on quality of life in adults with autism spectrum disorder.
    Lauren Bishop‐Fitzpatrick, Leann Smith DaWalt, Jan S. Greenberg, Marsha R. Mailick.
    Autism Research. February 28, 2017
    As the number of adults with autism spectrum disorder (ASD) grows, the need to identify modifiable correlates of positive outcomes and quality of life (QoL) gains in importance. Research indicates that perceived stress is significantly correlated with QoL in adults with ASD. Studies in the general population of individuals without disabilities indicate that greater participation in social and recreational activities may lessen the negative impact of perceived stress on well‐being, and this association may also hold among adults with ASD. We hypothesized that: (1) perceived stress would be negatively associated with QoL; and (2) higher frequency of participation in social activities and recreational activities would moderate the relationship between perceived stress and QoL. We used data collected from 60 adults with ASD aged 24–55 and their mothers to address our hypotheses. Findings indicate that adults with ASD with higher perceived stress are likely to have poorer QoL. Furthermore, greater participation in recreational activities buffers the impact of perceived stress on QoL, but no buffering effect was observed for participation in social activities. These findings suggest that interventions and services that provide supports and opportunities for participation in recreational activities may help adults with ASD manage their stress and lead to better QoL. Autism Res 2017, 10: 973–982. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    February 28, 2017   doi: 10.1002/aur.1753   open full text
  • Parent‐delivered early intervention in infants at risk for ASD: Effects on electrophysiological and habituation measures of social attention.
    Emily J.H. Jones, Geraldine Dawson, Jean Kelly, Annette Estes, Sara Jane Webb.
    Autism Research. February 28, 2017
    Prospective longitudinal studies of infants with older siblings with autism spectrum disorder (ASD) have indicated that differences in the neurocognitive systems underlying social attention may emerge prior to the child meeting ASD diagnostic criteria. Thus, targeting social attention with early intervention might have the potential to alter developmental trajectories for infants at high risk for ASD. Electrophysiological and habituation measures of social attention were collected at 6, 12, and 18 months in a group of high‐risk infant siblings of children with ASD (N = 33). Between 9 and 11 months of age, infant siblings received a parent‐delivered intervention, promoting first relationships (PFR), (n = 19) or on‐going assessment without intervention (n = 14). PFR has been previously shown to increase parental responsivity to infant social communicative cues and infant contingent responding. Compared to infants who only received assessment and monitoring, infants who received the intervention showed improvements in neurocognitive metrics of social attention, as reflected in a greater reduction in habituation times to face versus object stimuli between 6 and 12 months, maintained at 18 months; a greater increase in frontal EEG theta power between 6 and 12 months; and a more comparable P400 response to faces and objects at 12 months. The high‐risk infants who received the intervention showed a pattern of responses that appeared closer to the normative responses of two groups of age‐matched low‐risk control participants. Though replication is necessary, these results suggest that early parent‐mediated intervention has the potential to impact the brain systems underpinning social attention in infants at familial risk for ASD. Autism Res 2017, 10: 961–972. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    February 28, 2017   doi: 10.1002/aur.1754   open full text
  • Atypical physiological orienting to direct gaze in low‐functioning children with autism spectrum disorder.
    Terhi M. Helminen, Jukka M. Leppänen, Kai Eriksson, Arto Luoma, Jari K. Hietanen, Anneli Kylliäinen.
    Autism Research. February 28, 2017
    Reduced use of eye contact is a prominent feature in individuals with autism spectrum disorder (ASD). It has been proposed that direct gaze does not capture the attention of individuals with ASD. Experimental evidence is, however, mainly restricted to relatively high‐functioning school‐aged children or adults with ASD. This study investigated whether 2–5‐year‐old low‐functioning children with severe ASD differ from control children in orienting to gaze stimuli, as measured with the heart rate deceleration response. Responses were measured to computerized presentations of dynamic shifts of gaze direction either toward (direct) or away (averted) from the observing child. The results showed a significant group by gaze direction interaction effect on heart rate responses (permuted P = .004), reflecting a stronger orienting response to direct versus averted gaze in typically developing (N = 17) and developmentally delayed (N = 16) children but not in children with ASD (N = 12). The lack of enhanced orienting response to direct gaze in the ASD group was not caused by a lack of looking at the eye region, as confirmed by eye tracking. The results suggest that direct gaze is not a socially salient, attention‐grabbing signal for low‐functioning children with ASD. Autism Res 2017, 10: 810–820. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    February 28, 2017   doi: 10.1002/aur.1738   open full text
  • Atypical pupillary light reflex in 2–6‐year‐old children with autism spectrum disorders.
    Dinalankara M. R. Dinalankara, Judith H. Miles, T. Nicole Takahashi, Gang Yao.
    Autism Research. February 11, 2017
    The purpose of this study was to investigate pupillary light reflex (PLR) in 2–6‐years‐old children with autism spectrum disorders (ASD). A total of 117 medication‐free 2–6‐year‐old boys participated in this study. Sixty participants were diagnosed with ASD (the “ASD group”) and the other 57 were in the control group of typical development (the “TD group”). A questionnaire was completed by the parent/guardian for assessing potential dysfunctions in the autonomic nervous system (ANS). The base pupil radius, PLR latency, and constriction time showed a significant age‐related trend in both the ASD and TD groups. The base pupil size increased with age in the typically developing children, but not in the ASD group. The ASD group showed more symptoms related to ANS dysfunctions. An association between abnormal sweating with base pupil radius and PLR constriction was observed in the TD group but not the ASD group. The different association of PLR parameters with ANS dysfunction may suggest disrupted autonomic controls in children with ASD. Autism Res 2017, 10: 829–838. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    February 11, 2017   doi: 10.1002/aur.1745   open full text
  • The influence of sex and age on prevalence rates of comorbid conditions in autism.
    Kaustubh Supekar, Tara Iyer, Vinod Menon.
    Autism Research. February 11, 2017
    Individuals with ASD frequently experience one or more comorbid conditions. Here, we investigate the influence of sex and age—two important, yet understudied factors—on ten common comorbid conditions in ASD, using cross‐sectional data from 4790 individuals with ASD and 1,842,575 individuals without ASD. Epilepsy, ADHD, and CNS/cranial anomalies showed exceptionally large proportions in both male (>19%) and female (>15%), children/adolescents with ASD. Notably, these prevalence rates decreased drastically with age in both males and females. In contrast, the prevalence of schizophrenia increased with age affecting a disproportionately large number of older (≥35 year) adult males (25%), compared to females (7.7%), with ASD. Bowel disorders showed a complex U‐pattern accompanied by changes in sex disparity with age. These results highlight crucial differences between cross‐sectional comorbidity patterns and their interactions with sex and age, which may aid in the development of effective sex‐ and age‐specific diagnostic/treatment strategies for ASD and comorbid conditions. Autism Res 2017, 10: 778–789. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    February 11, 2017   doi: 10.1002/aur.1741   open full text
  • Infant muscle tone and childhood autistic traits: A longitudinal study in the general population.
    Fadila Serdarevic, Akhgar Ghassabian, Tamara van Batenburg‐Eddes, Tonya White, Laura M. E. Blanken, Vincent W. V. Jaddoe, Frank C. Verhulst, Henning Tiemeier.
    Autism Research. February 09, 2017
    In a longitudinal population‐based study of 2,905 children, we investigated if infants' neuromotor development was associated with autistic traits in childhood. Overall motor development and muscle tone were examined by trained research assistants with an adapted version of Touwen's Neurodevelopmental Examination between ages 2 and 5 months. Tone was assessed in several positions and items were scored as normal, low, or high tone. Parents rated their children's autistic traits with the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist at 6 years. We defined clinical PDP if scores were >98th percentile of the norm population. Diagnosis of autism spectrum disorder (ASD) was clinically confirmed in 30 children. We observed a modest association between overall neuromotor development in infants and autistic traits. Low muscle tone in infancy predicted autistic traits measured by SRS (adjusted beta = 0.05, 95% CI for B: 0.00–0.02, P = 0.01), and PDP (adjusted beta = 0.08, 95% CI for B: 0.04–0.10, P < 0.001). Similar results emerged for the association of low muscle tone and clinical PDP (adjusted OR = 1.36, 95% CI: 1.08–1.72, P = 0.01) at age 6 years. Results remained unchanged if adjusted for child intelligence. There was no association between high muscle tone and SRS or PDP. Exclusion of children with ASD diagnosis did not change the association. This large study showed a prospective association of infant muscle tone with autistic traits in childhood. Our findings suggest that early detection of low muscle tone might be a gateway to improve early diagnosis of ASD. Autism Res 2017, 10: 757–768. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    February 09, 2017   doi: 10.1002/aur.1739   open full text
  • Distinct profiles of social skill in adults with autism spectrum disorder and schizophrenia.
    Kerrianne E. Morrison, Amy E. Pinkham, David L. Penn, Skylar Kelsven, Kelsey Ludwig, Noah J. Sasson.
    Autism Research. January 23, 2017
    Overlapping social impairments in Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ) contributed to decades of diagnostic confusion that continues to this day in some clinical settings. The current study provides the first direct and detailed comparison of social behavior in the two disorders by identifying profiles of social skill in adults with ASD (n = 54), SCZ (n = 54), and typically developing (TD) controls (n = 56) during a real‐world social interaction. ASD and SCZ groups exhibited poorer social skill, both overall and on most discrete abilities, relative to the TD group. Direct comparison of ASD to SCZ revealed distinct behavioral profiles, with ASD uniquely characterized by fewer interactive behaviors, and SCZ characterized by greater impaired gaze and flat/inappropriate affective responses. Additionally, IQ was associated with both overall social skill and many discrete social skills in SCZ, but was largely unrelated to social skill in ASD. These results indicate that overlapping social deficits in ASD and SCZ are comprised of both shared and distinct social skill impairments. The largest distinctions—reduced social reciprocity but better expressivity in ASD relative to SCZ, and a greater role of IQ in social skill for SCZ than ASD—highlight disorder‐specific features that can improve etiological understanding, diagnostic differentiation, and treatment strategies. Autism Res 2017, 10: 878–887. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
    January 23, 2017   doi: 10.1002/aur.1734   open full text
  • Evidence of a reduction over time in the behavioral severity of autistic disorder diagnoses.
    Andrew J.O. Whitehouse, Matthew N. Cooper, Keely Bebbington, Gail Alvares, Ashleigh Lin, John Wray, Emma J. Glasson.
    Autism Research. January 19, 2017
    The increasing prevalence of Autism Spectrum Disorders (ASD) may in part be due to a shift in the diagnostic threshold that has led to individuals with a less severe behavioral phenotype receiving a clinical diagnosis. This study examined whether there were changes over time in the qualitative and quantitative phenotype of individuals who received the diagnosis of Autistic Disorder. Data were from a prospective register of new diagnoses in Western Australia (n = 1252). From 2000 to 2006, we examined differences in both the percentage of newly diagnosed cases that met each criterion as well as severity ratings of the behaviors observed (not met, partially met, mild/moderate and extreme). Linear regression determined there was a statistically significant reduction from 2000 to 2006 in the percentage of new diagnoses meeting two of 12 criteria. There was also a reduction across the study period in the proportion of new cases rated as having extreme severity on six criteria. There was a reduction in the proportion of individuals with three or more criteria rated as extreme from 2000 (16.0%) to 2006 (1.6%), while percentage of new cases with no “extreme” rating on any criteria increased from 58.5% to 86.6% across the same period. This study provides the first clear evidence of a reduction over time in the behavioral severity of individuals diagnosed with Autistic Disorder during a period of stability in diagnostic criteria. A shift toward diagnosing individuals with less severe behavioral symptoms may have contributed to the increasing prevalence of Autistic Disorder diagnoses. Autism Res 2017, 10: 179–187. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 19, 2017   doi: 10.1002/aur.1740   open full text
  • Strategies of readers with autism when responding to inferential questions: An eye‐movement study.
    Martina Micai, Holly Joseph, Mila Vulchanova, David Saldaña.
    Autism Research. December 02, 2016
    Previous research suggests that individuals with autism spectrum disorder (ASD) have difficulties with inference generation in reading tasks. However, most previous studies have examined how well children understand a text after reading or have measured on‐line reading behavior without response to questions. The aim of this study was to investigate the online strategies of children and adolescents with autism during reading and at the same time responding to a question by monitoring their eye movements. The reading behavior of participants with ASD was compared with that of age‐, language‐, nonverbal intelligence‐, reading‐, and receptive language skills‐matched participants without ASD (control group). The results showed that the ASD group were as accurate as the control group in generating inferences when answering questions about the short texts, and no differences were found between the two groups in the global paragraph reading and responding times. However, the ASD group displayed longer gaze latencies on a target word necessary to produce an inference. They also showed more regressions into the word that supported the inference compared to the control group after reading the question, irrespective of whether an inference was required or not. In conclusion, the ASD group achieved an equivalent level of inferential comprehension, but showed subtle differences in reading comprehension strategies compared to the control group. Autism Res 2017, 10: 888–900. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    December 02, 2016   doi: 10.1002/aur.1731   open full text
  • The impact of caregiver‐mediated JASPER on child restricted and repetitive behaviors and caregiver responses.
    Clare Harrop, Amanda Gulsrud, Wendy Shih, Lilit Hovsepyan, Connie Kasari.
    Autism Research. December 02, 2016
    Restricted and repetitive behaviors (RRBs) are a core feature of autism spectrum disorder (ASD). Compared to the social‐communication impairments, we know considerably less about why children engage in RRBs and if and how to intervene with these behaviors. As a result, early intervention has typically focused on social‐communication. In this study, we were interested in understanding how child RRBs changed following an intervention targeting social‐communication behaviors and if caregiver training changed how they responded to their child's RRBs. Eighty‐six toddlers with ASD and their caregivers received one of two interventions: caregivers were either actively coached while playing with their child (JASPER) or attended information sessions about ASD. On three different occasions (when they entered the study, following 10 weeks of intervention and 6‐months after) caregivers were filmed playing with their child. From these recordings, we coded child RRBs and caregiver responses to these behaviors. Child RRBs remained relatively stable following intervention in both groups, but increased when the children returned at 6‐months. Caregivers who received one‐on‐one coaching (JASPER) responded to a greater number of their child's RRBs and their responses were rated as more successful. Our study showed that a short‐term social‐communication intervention delivered through caregivers had “spillover effects” on how they also responded to their child's RRBs. Interventions targeting social‐communication behaviors should also examine how these treatments affect child RRBs and how caregiver responses to these behaviors may change following training. Autism Res 2017, 10: 983–992. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    December 02, 2016   doi: 10.1002/aur.1732   open full text
  • Auditory processing in noise is associated with complex patterns of disrupted functional connectivity in autism spectrum disorder.
    Fahimeh Mamashli, Sheraz Khan, Hari Bharadwaj, Konstantinos Michmizos, Santosh Ganesan, Keri‐Lee A. Garel, Javeria Ali Hashmi, Martha R. Herbert, Matti Hämäläinen, Tal Kenet.
    Autism Research. December 02, 2016
    Autism spectrum disorder (ASD) is associated with difficulty in processing speech in a noisy background, but the neural mechanisms that underlie this deficit have not been mapped. To address this question, we used magnetoencephalography to compare the cortical responses between ASD and typically developing (TD) individuals to a passive mismatch paradigm. We repeated the paradigm twice, once in a quiet background, and once in the presence of background noise. We focused on both the evoked mismatch field (MMF) response in temporal and frontal cortical locations, and functional connectivity with spectral specificity between those locations. In the quiet condition, we found common neural sources of the MMF response in both groups, in the right temporal gyrus and inferior frontal gyrus (IFG). In the noise condition, the MMF response in the right IFG was preserved in the TD group, but reduced relative to the quiet condition in ASD group. The MMF response in the right IFG also correlated with severity of ASD. Moreover, in noise, we found significantly reduced normalized coherence (deviant normalized by standard) in ASD relative to TD, in the beta band (14–25 Hz), between left temporal and left inferior frontal sub‐regions. However, unnormalized coherence (coherence during deviant or standard) was significantly increased in ASD relative to TD, in multiple frequency bands. Our findings suggest increased recruitment of neural resources in ASD irrespective of the task difficulty, alongside a reduction in top‐down modulations, usually mediated by the beta band, needed to mitigate the impact of noise on auditory processing. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 631–647. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    December 02, 2016   doi: 10.1002/aur.1714   open full text
  • Mid‐childhood outcomes of infant siblings at familial high‐risk of autism spectrum disorder.
    Elizabeth Shephard, Bosiljka Milosavljevic, Greg Pasco, Emily J. H. Jones, Teodora Gliga, Francesca Happé, Mark H. Johnson, Tony Charman,.
    Autism Research. November 29, 2016
    Almost 20% of infants with an older sibling with autism spectrum disorder (ASD) exhibit ASD themselves by age 3 years. The longer‐term outcomes of high‐risk infants are less clear. We examined symptoms of ASD, attention‐deficit/hyperactivity disorder (ADHD) and anxiety, language, IQ, and adaptive behaviour at age 7 years in high‐ and low‐risk children prospectively studied since the first year of life. Clinical outcomes were compared between high‐risk children who met diagnostic criteria for ASD at age 7 (HR‐ASD‐7 group, n = 15), high‐risk children without ASD (HR‐Non‐ASD‐7 group, n = 24), and low‐risk control children (LR group, n = 37). Diagnostic stability between age 3 and 7 years was moderate, with five children who did not meet diagnostic criteria for ASD at age 3 years being assigned the diagnosis at age 7, and three children showing the opposite pattern. The HR‐ASD‐7 group showed elevated ADHD and anxiety symptoms and had lower adaptive behaviour scores than LR controls. The HR‐Non‐ASD‐7 group had higher repetitive behaviour, lower adaptive functioning and elevated scores on one anxiety subscale (Separation Anxiety) compared to LR controls, but evidence for subclinical ASD symptoms (the broader autism phenotype, BAP) was limited in the group as a whole, although we identified a subgroup with elevated ASD traits. The difficulties experienced by high‐risk siblings at school‐age extend beyond ASD symptoms. The pattern of difficulties exhibited by the HR‐ASD‐7 group may inform our understanding of developmental trajectories of co‐occurring psychopathology in ASD. Autism Res 2017, 10: 546–557. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 29, 2016   doi: 10.1002/aur.1733   open full text
  • Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD.
    Shulamite A. Green, Leanna Hernandez, Susan Y. Bookheimer, Mirella Dapretto.
    Autism Research. November 29, 2016
    Recent evidence for abnormal thalamic connectivity in autism spectrum disorders (ASD) and sensory processing disorders suggests the thalamus may play a role in sensory over‐responsivity (SOR), an extreme negative response to sensory stimuli, which is common in ASD. However, there is yet little understanding of changes in thalamic connectivity during exposure to aversive sensory inputs in individuals with ASD. In particular, the pulvinar nucleus of the thalamus is implicated in atypical sensory processing given its role in selective attention, regulation, and sensory integration. This study aimed to examine the role of pulvinar connectivity in ASD during mildly aversive sensory input. Functional magnetic resonance imaging was used to examine connectivity with the pulvinar during exposure to mildly aversive auditory and tactile stimuli in 38 youth (age 9–17; 19 ASD, 19 IQ‐matched typically developing (TD)). Parents rated children's SOR severity on two standard scales. Compared to TD, ASD participants displayed aberrant modulation of connectivity between pulvinar and cortex (including sensory‐motor and prefrontal regions) during sensory stimulation. In ASD participants, pulvinar‐amygdala connectivity was correlated with severity of SOR symptoms. Deficits in modulation of thalamocortical connectivity in youth with ASD may reflect reduced thalamo‐cortical inhibition in response to sensory stimulation, which could lead to difficulty filtering out and/or integrating sensory information. An increase in amygdala connectivity with the pulvinar might be partially responsible for deficits in selective attention as the amygdala signals the brain to attend to distracting sensory stimuli. Autism Res 2017, 10: 801–809. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 29, 2016   doi: 10.1002/aur.1726   open full text
  • Investigating diagnostic bias in autism spectrum conditions: An item response theory analysis of sex bias in the AQ‐10.
    Aja Louise Murray, Carrie Allison, Paula L. Smith, Simon Baron‐Cohen, Tom Booth, Bonnie Auyeung.
    Autism Research. November 28, 2016
    Diagnostic bias is a concern in autism spectrum conditions (ASC) where prevalence and presentation differ by sex. To ensure that females with ASC are not under‐identified, it is important that ASC screening tools do not systematically underestimate autistic traits in females relative to males. We evaluated whether the AQ‐10, a brief screen for ASC recommended by the National Institute of Clinical Excellence in cases of suspected ASC, exhibits such a bias. Using an item response theory approach, we evaluated differential item functioning and differential test functioning. We found that although individual items showed some sex bias, these biases at times favored males and at other times favored females. Thus, at the level of test scores the item‐level biases cancelled out to give an unbiased overall score. Results support the continued use of the AQ‐10 sum score in its current form; however, suggest that caution should be exercised when interpreting responses to individual items. The nature of the item level biases could serve as a guide for future research into how ASC affects males and females differently. Autism Res 2017, 10: 790–800. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 28, 2016   doi: 10.1002/aur.1724   open full text
  • Autism and emotional face‐viewing.
    Jakob Åsberg Johnels, Daniel Hovey, Nicole Zürcher, Loyse Hippolyte, Eric Lemonnier, Christopher Gillberg, Nouchine Hadjikhani.
    Autism Research. November 28, 2016
    Atypical patterns of face‐scanning in individuals with autism spectrum disorder (ASD) may contribute to difficulties in social interactions, but there is little agreement regarding what exactly characterizes face‐viewing in ASD. In addition, little research has examined how face‐viewing is modulated by the emotional expression of the stimuli, in individuals with or without ASD. We used eye‐tracking to explore viewing patterns during perception of dynamic emotional facial expressions in relatively large groups of individuals with (n = 57) and without ASD (n = 58) and examined diagnostic‐ and age‐related effects, after subgrouping children and adolescents (≤18 years), on the one hand, and adults (>18 years), on the other. Results showed that children/adolescents with ASD fixated the mouth of happy and angry faces less than their typically developing (TD) peers, and conversely looked more to the eyes of happy faces. Moreover, while all groups fixated the mouth in happy faces more than in other expressions, children/adolescents with ASD did relatively less so. Correlation analysis showed a similar lack of relative orientation towards the mouth of smiling faces in TD children/adolescents with high autistic traits, as measured by the Autism‐Spectrum Quotient (AQ). Among adults, participants with ASD only attended less to the eyes for neutral faces. Our study shows that the emotional content of a face influences gaze behaviour, and that this effect is not fully developed in children/adolescents with ASD. Interestingly, this lack of differentiation observed in the younger ASD group was also seen in younger TD individuals with higher AQ scores. Autism Res 2017, 10: 901–910. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 28, 2016   doi: 10.1002/aur.1730   open full text
  • Executive functioning in men and women with an autism spectrum disorder.
    Michelle Kiep, Annelies A. Spek.
    Autism Research. November 22, 2016
    Executive functioning (EF) is thought to be linked to autism spectrum disorders (ASD) specific symptoms. The majority of research has focused on children and adolescents with ASD and, therefore, little is known about EF in adults. Furthermore, little is known about gender differences. Ninety‐nine men and forty women with ASD were compared with and 35 neurotypical men 25 neurotypical women. Participants were matched on age, total intelligence, and verbal ability. The following instruments were used to measure executive functioning: digit span and letter and number sequencing of the WAIS‐III, Tower of Hanoi, WCST, and Verbal fluency. Multiple analysis of variance was conducted to determine group differences. Women with ASD performed worse on the working memory tasks of the WAIS‐III than neurotypical women. Furthermore, women with ASD had more perseverations on the WCST than neurotypical women. The gender comparison in the ASD group showed differences in performance on mental flexibility (WCST), working memory (WAIS‐III), generativity and self‐monitoring (Verbal fluency). However, these differences were unequivocal and no gender specific cognitive profile could be pinpointed. Individual strengths and frailties should be highlighted in clinical practice, as impairments in EF can be under influence of the overall cognitive abilities of the individual. Furthermore, gender differences were found. This could explain differences in representation of ASD symptoms in both groups. These differences show how important thorough diagnostics are. Autism Res 2017, 10: 940–948. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 22, 2016   doi: 10.1002/aur.1721   open full text
  • Ensemble perception of color in autistic adults.
    John Maule, Kirstie Stanworth, Elizabeth Pellicano, Anna Franklin.
    Autism Research. November 22, 2016
    Dominant accounts of visual processing in autism posit that autistic individuals have an enhanced access to details of scenes [e.g., weak central coherence] which is reflected in a general bias toward local processing. Furthermore, the attenuated priors account of autism predicts that the updating and use of summary representations is reduced in autism. Ensemble perception describes the extraction of global summary statistics of a visual feature from a heterogeneous set (e.g., of faces, sizes, colors), often in the absence of local item representation. The present study investigated ensemble perception in autistic adults using a rapidly presented (500 msec) ensemble of four, eight, or sixteen elements representing four different colors. We predicted that autistic individuals would be less accurate when averaging the ensembles, but more accurate in recognizing individual ensemble colors. The results were consistent with the predictions. Averaging was impaired in autism, but only when ensembles contained four elements. Ensembles of eight or sixteen elements were averaged equally accurately across groups. The autistic group also showed a corresponding advantage in rejecting colors that were not originally seen in the ensemble. The results demonstrate the local processing bias in autism, but also suggest that the global perceptual averaging mechanism may be compromised under some conditions. The theoretical implications of the findings and future avenues for research on summary statistics in autism are discussed. Autism Res 2017, 10: 839–851. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 22, 2016   doi: 10.1002/aur.1725   open full text
  • Prenatal toxoplasmosis antibody and childhood autism.
    Marisa N. Spann, Andre Sourander, Heljä‐Marja Surcel, Susanna Hinkka‐Yli‐Salomäki, Alan S. Brown.
    Autism Research. November 22, 2016
    There is evidence that some maternal infections during the prenatal period are associated with neurodevelopmental disorders, such as childhood autism. However, the association between autism and Toxoplasma gondii (T. gondii), an intracellular parasite, remains unclear. The authors examined whether serologically confirmed maternal antibodies to T. gondii are associated with odds of childhood autism in offspring. The study is based on a nested case‐control design of a large national birth cohort (N = 1.2 million) and the national psychiatric registries in Finland. There were 874 cases of childhood autism and controls matched 1:1 on date of birth, sex, birthplace and residence in Finland. Maternal sera were prospectively assayed from a national biobank for T. gondii IgM and IgG antibodies; IgG avidity analyses were also performed. High maternal T. gondii IgM antibody was associated with a significantly decreased odds of childhood autism. Low maternal T. gondii IgG antibody was associated with increased offspring odds of autism. In women with high T. gondii IgM antibodies, the IgG avidity was high for both cases and controls, with the exception of three controls. The findings suggest that the relationship between maternal T. gondii antibodies and odds of childhood autism may be related to the immune response to this pathogen or the overall activation of the immune system. Autism Res 2017, 10: 769–777. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 22, 2016   doi: 10.1002/aur.1722   open full text
  • Meta‐analysis of neuropsychological measures of executive functioning in children and adolescents with high‐functioning autism spectrum disorder.
    Chun Lun Eric Lai, Zoe Lau, Simon S. Y. Lui, Eugenia Lok, Venus Tam, Quinney Chan, Koi Man Cheng, Siu Man Lam, Eric F. C. Cheung.
    Autism Research. November 22, 2016
    Existing literature on the profile of executive dysfunction in autism spectrum disorder showed inconsistent results. Age, comorbid attention‐deficit/hyperactivity disorder (ADHD) and cognitive abilities appeared to play a role in confounding the picture. Previous meta‐analyses have focused on a few components of executive functions. This meta‐analysis attempted to delineate the profile of deficit in several components of executive functioning in children and adolescents with high‐functioning autism spectrum disorder (HFASD). Ninety‐eight English published case‐control studies comparing children and adolescents with HFASD with typically developing controls using well‐known neuropsychological measures to assess executive functions were included. Results showed that children and adolescents with HFASD were moderately impaired in verbal working memory (g = 0.67), spatial working memory (g = 0.58), flexibility (g = 0.59), planning (g = 0.62), and generativity (g = 0.60) except for inhibition (g = 0.41). Subgroup analysis showed that impairments were still significant for flexibility (g = 0.57–0.61), generativity (g = 0.52–0.68), and working memory (g = 0.49–0.56) in a sample of autism spectrum disorder (ASD) subjects without comorbid ADHD or when the cognitive abilities of the ASD group and the control group were comparable. This meta‐analysis confirmed the presence of executive dysfunction in children and adolescents with HFASD. These deficits are not solely accounted for by the effect of comorbid ADHD and the general cognitive abilities. Our results support the executive dysfunction hypothesis and contribute to the clinical understanding and possible development of interventions to alleviate these deficits in children and adolescents with HFASD. Autism Res 2017, 10: 911–939. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 22, 2016   doi: 10.1002/aur.1723   open full text
  • Diagnostic model generated by MRI‐derived brain features in toddlers with autism spectrum disorder.
    Xiang Xiao, Hui Fang, Jiansheng Wu, ChaoYong Xiao, Ting Xiao, Lu Qian, FengJing Liang, Zhou Xiao, Kang Kang Chu, Xiaoyan Ke.
    Autism Research. November 22, 2016
    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder mainly showed atypical social interaction, communication, and restricted, repetitive patterns of behavior, interests and activities. Now clinic diagnosis of ASD is mostly based on psychological evaluation, clinical observation and medical history. All these behavioral indexes could not avoid defects such as subjectivity and reporter‐dependency. Therefore researchers devoted themselves to seek relatively stable biomarkers of ASD as supplementary diagnostic evidence. The goal of present study is to generate relatively stable predictive model based on anatomical brain features by using machine learning technique. Forty‐six ASD children and thirty‐nine development delay children aged from 18 to 37 months were evolved in. As a result, the predictive model generated by regional average cortical thickness of regions with top 20 highest importance of random forest classifier showed best diagnostic performance. And random forest was proved to be the optimal approach for neuroimaging data mining in small size set and thickness‐based classification outperformed volume‐based classification and surface area‐based classification in ASD. The brain regions selected by the models might attract attention and the idea of considering biomarkers as a supplementary evidence of ASD diagnosis worth exploring. Autism Res 2017, 0: 000–000. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 620–630. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 22, 2016   doi: 10.1002/aur.1711   open full text
  • Incidental brain MRI findings in an autism twin study.
    Julio C. Monterrey, Jennifer Philips, Sue Cleveland, Serena Tanaka, Patrick Barnes, Joachim F. Hallmayer, Alan L. Reiss, Laura C. Lazzeroni, Antonio Y. Hardan.
    Autism Research. November 22, 2016
    Brain magnetic resonance imaging (MRI) studies suggest the prevalence of asymptomatic “incidental” findings (IF) in autism spectrum disorder (ASD) is similar to that of neurotypically developing (NT) controls. However, given the causes of IF may include both genetic and environmental factors, a twin study would facilitate comparing brain IF between ASD and NT subjects. MRI scans were examined to assess the prevalence of brain IF in twin “case pairs” (at least one twin with diagnosis of ASD) and twin “control pairs” (NT). Fifty case pairs and thirty‐two control pairs were analyzed. IF were found in 68% of subjects with ASD, 71% of unaffected ASD siblings, and in 58% of control subjects (P = 0.4). IF requiring clinical follow‐up occurred more frequently in subjects with ASD compared to NT controls (17% vs. 5%, respectively; P = 0.02). The concordance rate of IF in twins was 83%. A mixed effects model found younger age, male sex, and “family environment” to be significantly associated with IF. There was no difference in the prevalence rate of IF between ASD subjects and NT controls. More IF required clinical follow‐up in ASD subjects compared to NT controls. The prevalence rate of IF observed in this twin study was higher than rates previously reported in singleton studies. Our results suggest the shared environment of twins – perhaps in utero – increases the risk of brain IF. Brain MRI in the initial work‐up of ASD may be indicated in twins, especially in males. Autism Res 2017, 10: 113–120. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 22, 2016   doi: 10.1002/aur.1720   open full text
  • The salience of the self: Self‐referential processing and internalizing problems in children and adolescents with autism spectrum disorder.
    Catherine A. Burrows, Lauren V. Usher, Peter C. Mundy, Heather A. Henderson.
    Autism Research. November 20, 2016
    Children and adolescents with autism spectrum disorder (ASD) demonstrate atypical processing of, and memory for, self‐referenced information, which may contribute to the heightened rates of co‐occurring internalizing problems. We assessed affective and cognitive aspects of self‐referential processing in verbally‐fluent children with ASD (N = 79), and an age‐matched comparison sample (COM, N = 73) of children without an autism diagnosis. We examined group differences in these two aspects of the self‐system, and their joint contributions to individual differnces in internalizing problems. Using a self‐referenced memory (SRM) task, participants indicated whether a series of positive and negative trait adjectives described themselves and a well‐known fictional character. Participants were then surprised with a recognition memory test on the same adjectives. Overall, individuals with ASD showed a reduction in the extent to which they preferentially endorsed positive over negative trait adjectives about themselves, and a reduction in their preferential memory for self‐ over other‐referenced information. Across the full sample, these two aspects of self‐referential processing jointly predicted self‐reported internalizing problems. Specifically, self‐evaluations were strongly and inversely associated with internalizing problems but only for children with relatively high SRM. These findings suggest that the salience of the self influences the extent to which affective self‐evaluations impact emotional functioning for youth both with and without ASD. Implications for basic (e.g., developmental) and translational (e.g., intervention) research are discussed. Autism Res 2017, 10: 949–960. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 20, 2016   doi: 10.1002/aur.1727   open full text
  • Gender differences in autism spectrum disorders: Divergence among specific core symptoms.
    Anita Beggiato, Hugo Peyre, Anna Maruani, Isabelle Scheid, Maria Rastam, Frederique Amsellem, Carina I. Gillberg, Marion Leboyer, Thomas Bourgeron, Christopher Gillberg, Richard Delorme.
    Autism Research. November 03, 2016
    Community‐based studies have consistently shown a sex ratio heavily skewed towards males in autism spectrum disorders (ASD). The factors underlying this predominance of males are largely unknown, but the way girls score on standardized categorical diagnostic tools might account for the underrecognition of ASD in girls. Despite the existence of different norms for boys and girls with ASD on several major screening tests, the algorithm of the Autism Diagnosis Interview‐Revised (ADI‐R) has not been reformulated. The aim of our study was to investigate which ADI‐R items discriminate between males and females, and to evaluate their weighting in the final diagnosis of autism. We then conducted discriminant analysis (DA) on a sample of 594 probands including 129 females with ASD, recruited by the Paris Autism Research International Sibpair (PARIS) Study. A replication analysis was run on an independent sample of 1716 probands including 338 females with ASD, recruited through the Autism Genetics Resource Exchange (AGRE) program. Entering the raw scores for all ADI‐R items as independent variables, the DA correctly classified 78.9% of males and 72.9% of females (P < 0.001) in the PARIS cohort, and 72.2% of males and 68.3% of females (P < 0.0001) in the AGRE cohort. Among the items extracted by the stepwise DA, four belonged to the ADI‐R algorithm used for the final diagnosis of ASD. In conclusion, several items of the ADI‐R that are taken into account in the diagnosis of autism significantly differentiates between males and females. The potential gender bias thus induced may participate in the underestimation of the prevalence of ASD in females. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 680–689. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 03, 2016   doi: 10.1002/aur.1715   open full text
  • Unique effects of The transporters animated series and of parental support on emotion recognition skills of children with ASD: Results of a randomized controlled trial.
    Tali Gev, Ruthie Rosenan, Ofer Golan.
    Autism Research. November 03, 2016
    Emotion recognition (ER) and understanding deficits are characteristic of autism spectrum disorder (ASD). The Transporters (TT) animated series has shown promising results in teaching children with ASD to recognize emotions, with mixed findings about generalization and maintenance of effects. This study aimed to evaluate the unique role of TT and of parental support in the acquisition, generalization, and maintenance of acquired ER skills in children with ASD. 77 Israeli children with high functioning ASD, aged 4–7 were randomly assigned into four groups according to a 2 × 2 design of the factors Series (TT, control series) and Parental Support (with/without). Thirty typically developing children, matched to the ASD groups on mental age, were tested with no intervention. Participants' ER (on three generalization levels) and emotional vocabulary (EV) were tested pre and post 8 weeks of intervention, and at 3 months' follow‐up. Compared to the control series, watching TT significantly improved children's ER skills at all generalization levels, with good skill maintenance. All groups improved equally on EV. The amount of parental support given, in the groups that had received it, contributed to the generalization and maintenance of ER skills. Autism severity negatively correlated with ER improvement. The current study provides evidence to the unique role of TT in ER skill acquisition, generalization, and maintenance in children with high functioning ASD. In addition, this study provides evidence for a successful cultural adaptation of TT to a non‐English speaking culture. Autism Res 2017, 10: 993–1003. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    November 03, 2016   doi: 10.1002/aur.1717   open full text
  • “Frank” presentations as a novel research construct and element of diagnostic decision‐making in autism spectrum disorder.
    Ashley de Marchena, Judith Miller.
    Autism Research. October 21, 2016
    Many individuals with ASD have a distinctive behavioral presentation that is recognizable within moments, a phenomenon we call “frank” ASD. This phenomenon has been discussed informally for decades, perhaps as “classic” ASD; however, there is no unitary “classic” presentation, and classic autism does not seem to correspond to level of functioning. Thus, neither “frank” nor “classic” autism has been delineated or studied as a research construct. To initiate the empirical study of frank ASD, we surveyed 151 clinicians, from a range of disciplines that diagnose ASD, about this phenomenon. Respondents completed a 13‐item questionnaire about frank ASD, which was analyzed using a mixed‐methods approach. Ninety‐seven percentage of respondents were familiar with the phenomenon. Respondents estimated that 40% of the ASD population has a frank presentation. Respondents reported the most highly specific behaviors associated with frank presentations were a general sense of impaired reciprocity, quality of eye contact, atypical vocal prosody, presence of motor mannerisms, and atypical gait or posture. In general, respondents reported detecting frank features rapidly, with the majority forming their impressions within the first ten minutes of interaction or observation. Although unstudied empirically, “frank” presentations of ASD are familiar to diagnosing clinicians, and appear to be based on behaviors both central to ASD diagnostic criteria (e.g., impaired reciprocity), and absent from diagnostic criteria (e.g., atypical gait or posture). We discuss these findings within the context of diagnostic decision‐making and behavioral phenotyping of ASD. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 653–662. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    October 21, 2016   doi: 10.1002/aur.1706   open full text
  • Neonatal thyroid hormone levels in association with autism spectrum disorder.
    Kristen Lyall, Meredith Anderson, Martin Kharrazi, Gayle C. Windham.
    Autism Research. October 14, 2016
    Thyroid hormones (TH) are critical in early neurodevelopment, but few studies have examined whether neonatal TH levels influence risk of autism spectrum disorder (ASD). This study linked California neonatal screening data with live birth and Department of Developmental Services records to examine newborn TH levels in relation to ASD. Thyroxine (T4) and thyroid‐stimulating hormone (TSH) levels were measured in newborn bloodspots as part of routine screening, in 1996 and 2002, respectively. Mean levels of T4 and TSH were compared between ASD cases and non‐cases. Four hundred forty‐seven thousand, fifty‐nine screened, singleton births from 1996 and 446,424 from 2002 were examined, including 4,818 ASD cases. Binomial regression, using categories of T4 and TSH percentiles was used to calculate crude and adjusted risk ratios (RR). Covariates included maternal and child factors, gestational age, and age at blood draw. No significant associations were found with TSH levels and ASD in crude or adjusted analyses. ASD cases had significantly lower mean T4 levels than non‐cases, but this association was no longer significant in adjusted analyses (RR in individuals in lowest 5th percentile of T4 levels = 1.13, 95% 0.93–1.37). However, this association appeared stronger in certain subgroup analyses, particularly among neonates with blood draw ≥48 hr from birth (RR = 1.67, 95% CI 1.08, 2.60), when TH levels become more stable. Thus, results from this large, population‐based study did not suggest strong associations between neonatal TH and ASD, but certain subgroups of newborns with the lowest T4 levels may have modestly increased ASD risk. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 585–592. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    October 14, 2016   doi: 10.1002/aur.1708   open full text
  • Stability of the acoustic startle response and its modulation in children with typical development and those with autism spectrum disorders: A one‐year follow‐up.
    Hidetoshi Takahashi, Takayuki Nakahachi, Andrew Stickley, Makoto Ishitobi, Yoko Kamio.
    Autism Research. October 14, 2016
    Auditory hyper‐reactivity is a common sensory–perceptual abnormality that interrupts behavioral adaptations in autism spectrum disorders (ASD). Recently, prolonged acoustic startle response (ASR) latency and hyper‐reactivity to weak acoustic stimuli were reported in children with ASD. Indexes of ASR and its modulation are known to be stable biological markers for translational research in the adult population. However, little is known about the stability of these indexes in children. Thus, the objective of our study was to investigate the stability of neurophysiological ASR indexes in children with ASD and typical development (TD). Participants included 12 children with ASD and 24 with TD. Mean startle magnitudes to acoustic stimuli presented at 65–105 dB in increments of 10 dB were analyzed. Average peak startle latency (PSL), ASR modulation of habituation, and prepulse inhibition were also analyzed. These startle measures were examined after a follow‐up period of 15.7 ± 5.1 months from baseline. At both baseline and in the follow‐up period, children with ASD had significantly greater startle magnitudes to weak stimuli of 65–85 dB and more prolonged PSL compared with controls. Intraclass correlation coefficients for these ASR measures between both periods were 0.499–0.705. None of the ASR measures differed significantly between the two periods. Our results suggest that prolonged PSL and greater startle magnitudes to weak stimuli in children with ASD might serve as moderately stable neurophysiological indexes of ASD. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 673–679. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    October 14, 2016   doi: 10.1002/aur.1710   open full text
  • Hyperactivity and male‐specific sleep deficits in the 16p11.2 deletion mouse model of autism.
    Christopher C. Angelakos, Adam J. Watson, W. Timothy O'Brien, Kyle S. Krainock, Thomas Nickl‐Jockschat, Ted Abel.
    Autism Research. October 14, 2016
    Sleep disturbances and hyperactivity are prevalent in several neurodevelopmental disorders, including autism spectrum disorders (ASDs) and attention deficit‐hyperactivity disorder (ADHD). Evidence from genome‐wide association studies indicates that chromosomal copy number variations (CNVs) are associated with increased prevalence of these neurodevelopmental disorders. In particular, CNVs in chromosomal region 16p11.2 profoundly increase the risk for ASD and ADHD, disorders that are more common in males than females. We hypothesized that mice hemizygous for the 16p11.2 deletion (16p11.2 del/+) would exhibit sex‐specific sleep and activity alterations. To test this hypothesis, we recorded activity patterns using infrared beam breaks in the home‐cage of adult male and female 16p11.2 del/+ and wildtype (WT) littermates. In comparison to controls, we found that both male and female 16p11.2 del/+ mice exhibited robust home‐cage hyperactivity. In additional experiments, sleep was assessed by polysomnography over a 24‐hr period. 16p11.2 del/+ male, but not female mice, exhibited significantly more time awake and significantly less time in non‐rapid‐eye‐movement (NREM) sleep during the 24‐hr period than wildtype littermates. Analysis of bouts of sleep and wakefulness revealed that 16p11.2 del/+ males, but not females, spent a significantly greater proportion of wake time in long bouts of consolidated wakefulness (greater than 42 min in duration) compared to controls. These changes in hyperactivity, wake time, and wake time distribution in the males resemble sleep disturbances observed in human ASD and ADHD patients, suggesting that the 16p11.2 del/+ mouse model may be a useful genetic model for studying sleep and activity problems in human neurodevelopmental disorders. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 572–584. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    October 14, 2016   doi: 10.1002/aur.1707   open full text
  • Social participation and its relation to internalizing symptoms among youth with autism spectrum disorder as they transition from high school.
    Julie Lounds Taylor, Ryan E. Adams, Somer L. Bishop.
    Autism Research. October 14, 2016
    In the present study, we examined how unstructured (e.g., spending time with friends or co‐workers) and structured (e.g., attending social events at a place of workshop, sports teams) social participation changed from before to after high school for youth with autism spectrum disorders (ASD), as well as the longitudinal and concurrent relations between social participation and internalizing symptoms. Participants included 36 families of youth with ASD who were all in their last year of high school at the first time point of data collection, and who were out of high school for an average of 9 months at the second time point. Social participation and internalizing symptoms were determined using parental report. There was no average change in the amount of unstructured social participation after high school exit, although substantial individual variability was observed. Participation in structured social activities significantly declined after high school exit. Youth who had more structured social participation while in high school were significantly more likely to have gains in their unstructured social participation after high school exit. Turning to relationships between internalizing and social activities, more internalizing symptoms while youth with ASD were in high school significantly predicted increasing social isolation after high school exit (both in terms of structured and unstructured activities). Results point to the likely need for additional supports during the transition to adulthood for youth with ASD who have internalizing problems. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 663–672. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    October 14, 2016   doi: 10.1002/aur.1709   open full text
  • Reduced visual disengagement but intact phasic alerting in young children with autism.
    Johan Lundin Kleberg, Emilia Thorup, Terje Falck‐Ytter.
    Autism Research. October 01, 2016
    Children with autism may have difficulties with visual disengagement—that is, inhibiting current fixations and orienting to new stimuli in the periphery. These difficulties may limit these children's ability to flexibly monitor the environment, regulate their internal states, and interact with others. In typical development, visual disengagement is influenced by a phasic alerting network that increases the processing speed of the visual system after salient events. The role of the phasic alerting effect in the putative atypical disengagement performance in autism spectrum disorder (ASD) is not known. Here, we compared visual disengagement in six‐year‐old children with autism (N = 18) and typically developing children (N = 17) matched for age and nonverbal IQ. We manipulated phasic alerting during a visual disengagement task by adding spatially nonpredictive sounds shortly before the onset of the visual peripheral targets. Children with ASD showed evidence of delayed disengagement compared to the control group. Sounds facilitated visual disengagement similarly in both groups, suggesting typical modulation by phasic alerting in ASD in the context of this task. These results support the view that atypical visual disengagement in ASD is related to other factors than atypicalities in the alerting network. Autism Res 2017, 10: 539–545. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
    October 01, 2016   doi: 10.1002/aur.1675   open full text
  • Exploring the relationship between cortical GABA concentrations, auditory gamma‐band responses and development in ASD: Evidence for an altered maturational trajectory in ASD.
    Russell G. Port, William Gaetz, Luke Bloy, Dah‐Jyuu Wang, Lisa Blaskey, Emily S. Kuschner, Susan E. Levy, Edward S. Brodkin, Timothy P.L. Roberts.
    Autism Research. October 01, 2016
    Autism spectrum disorder (ASD) is hypothesized to arise from imbalances between excitatory and inhibitory neurotransmission (E/I imbalance). Studies have demonstrated E/I imbalance in individuals with ASD and also corresponding rodent models. One neural process thought to be reliant on E/I balance is gamma‐band activity (Gamma), with support arising from observed correlations between motor, as well as visual, Gamma and underlying GABA concentrations in healthy adults. Additionally, decreased Gamma has been observed in ASD individuals and relevant animal models, though the direct relationship between Gamma and GABA concentrations in ASD remains unexplored. This study combined magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS) in 27 typically developing individuals (TD) and 30 individuals with ASD. Auditory cortex localized phase‐locked Gamma was compared to resting Superior Temporal Gyrus relative cortical GABA concentrations for both children/adolescents and adults. Children/adolescents with ASD exhibited significantly decreased GABA+/Creatine (Cr) levels, though typical Gamma. Additionally, these children/adolescents lacked the typical maturation of GABA+/Cr concentrations and gamma‐band coherence. Furthermore, children/adolescents with ASD additionally failed to exhibit the typical GABA+/Cr to gamma‐band coherence association. This altered coupling during childhood/adolescence may result in Gamma decreases observed in the adults with ASD. Therefore, individuals with ASD exhibit improper local neuronal circuitry maturation during a childhood/adolescence critical period, when GABA is involved in configuring of such circuit functioning. Provocatively a novel line of treatment is suggested (with a critical time window); by increasing neural GABA levels in children/adolescents with ASD, proper local circuitry maturation may be restored resulting in typical Gamma in adulthood. Autism Res 2017, 10: 593–607. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    October 01, 2016   doi: 10.1002/aur.1686   open full text
  • Beyond the hype and hope: Critical considerations for intranasal oxytocin research in autism spectrum disorder.
    Gail A. Alvares, Daniel S. Quintana, Andrew J.O. Whitehouse.
    Autism Research. September 21, 2016
    Extensive research efforts in the last decade have been expended into understanding whether intranasal oxytocin may be an effective therapeutic in treating social communication impairments in individuals with autism spectrum disorder (ASD). After much hyped early findings, subsequent clinical trials of longer‐term administration have yielded more conservative and mixed evidence. However, it is still unclear at this stage whether these more disappointing findings reflect a true null effect or are mitigated by methodological differences masking true effects. In this review, we comprehensively evaluate the rationale for oxytocin as a therapeutic, evaluating evidence from randomized controlled trials, case reports, and open‐label studies of oxytocin administration in individuals with ASD. The evidence to date, including reviews of preregistered trials, suggests a number of critical considerations for the design and interpretation of research in this area. These include considering the choice of ASD outcome measures, dosing and nasal spray device issues, and participant selection. Despite these limitations in the field to date, there remains significant potential for oxytocin to ameliorate aspects of the persistent and debilitating social impairments in individuals with ASD. Given the considerable media hype around new treatments for ASD, as well as the needs of eager families, there is an urgent need for researchers to prioritise considering such factors when conducting well‐designed and controlled studies to further advance this field. Autism Res 2017, 10: 25–41. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    September 21, 2016   doi: 10.1002/aur.1692   open full text
  • Reduced GABA and altered somatosensory function in children with autism spectrum disorder.
    Nicolaas A.J. Puts, Ericka L. Wodka, Ashley D. Harris, Deana Crocetti, Mark Tommerdahl, Stewart H. Mostofsky, Richard A.E. Edden.
    Autism Research. September 09, 2016
    Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods: GABA‐edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with‐ and without the presence of a slowly increasing sub‐threshold stimulus. Amplitude discrimination was measured with‐ and without the presence of an adapting stimulus, and frequency discrimination was measured. Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub‐threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    September 09, 2016   doi: 10.1002/aur.1691   open full text
  • The social responsiveness scale in relation to DSM IV and DSM5 ASD in Korean children.
    Keun‐Ah Cheon, Jee‐In Park, Yun‐Joo Koh, Jungeun Song, Hyun‐Joo Hong, Young‐Kee Kim, Eun‐Chung Lim, Hojang Kwon, Mina Ha, Myung‐Ho Lim, Ki‐Chung Paik, John N. Constantino, Bennett Leventhal, Young Shin Kim.
    Autism Research. September 08, 2016
    The Social Responsiveness Scale (SRS) is an autism rating scales in widespread use, with over 20 official foreign language translations. It has proven highly feasible for quantitative ascertainment of autistic social impairment in public health settings, however, little is known about the validity of the reinforcement in Asia populations or in references to DSM5. The current study aims to evaluate psychometric properties and cross‐cultural aspects of the SRS‐Korean version (K‐SRS).The study subjects were ascertained from three samples: a general sample from 3 regular education elementary schools (n=790), a clinical sample (n=154) of 6–12‐year‐olds from four psychiatric clinics, and an epidemiological sample of children with ASD, diagnosed using both DSM IV PDD, DSM5 ASD and SCD criteria (n=151). Their parents completed the K‐SRS and the Autism Spectrum Screening Questionnaire(ASSQ). Descriptive statistics, correlation analyses and principal components analysis (PCA) were performed on the total population. Mean total scores on the K‐SRS differed significantly between the three samples. ASSQ scores were significantly correlated with the K‐SRS T‐scores. PCA suggested a one‐factor solution for the total population.Our results indicate that the K‐SRS exhibits adequate reliability and validity for measuring ASD symptoms in Korean children with DSM IV PDD and DSM5 ASD. Our findings further suggest that it is difficult to distinguish SCD from other child psychiatric conditions using the K‐SRS.This is the first study to examine the relationship between the SRS subscales and DSM5‐based clinical diagnoses. This study provides cross‐cultural confirmation of the factor structure for ASD symptoms and traits measured by the SRS. Autism Res 2016, 9: 970–980. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    September 08, 2016   doi: 10.1002/aur.1671   open full text
  • Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound.
    Sara Jane Webb, Michelle M. Garrison, Raphael Bernier, Abbi M. McClintic, Bryan H. King, Pierre D. Mourad.
    Autism Research. September 01, 2016
    Current research suggests that incidence and heterogeneity of autism spectrum disorder (ASD) symptoms may arise through a variety of exogenous and/or endogenous factors. While subject to routine clinical practice and generally considered safe, there exists speculation, though no human data, that diagnostic ultrasound may also contribute to ASD severity, supported by experimental evidence that exposure to ultrasound early in gestation could perturb brain development and alter behavior. Here we explored a modified triple hit hypothesis [Williams & Casanova, ] to assay for a possible relationship between the severity of ASD symptoms and (1) ultrasound exposure (2) during the first trimester of pregnancy in fetuses with a (3) genetic predisposition to ASD. We did so using retrospective analysis of data from the SSC (Simon's Simplex Collection) autism genetic repository funded by the Simons Foundation Autism Research Initiative. We found that male children with ASD, copy number variations (CNVs), and exposure to first trimester ultrasound had significantly decreased non‐verbal IQ and increased repetitive behaviors relative to male children with ASD, with CNVs, and no ultrasound. These data suggest that heterogeneity in ASD symptoms may result, at least in part, from exposure to diagnostic ultrasound during early prenatal development of children with specific genetic vulnerabilities. These results also add weight to on‐going concerns expressed by the FDA about non‐medical use of diagnostic ultrasound during pregnancy. Autism Res 2017, 10: 472–484. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    September 01, 2016   doi: 10.1002/aur.1690   open full text
  • Disruption of visual circuit formation and refinement in a mouse model of autism.
    Ning Cheng, Maryam Khanbabaei, Kartikeya Murari, Jong M. Rho.
    Autism Research. August 16, 2016
    Aberrant connectivity is believed to contribute to the pathophysiology of autism spectrum disorder (ASD). Recent neuroimaging studies have increasingly identified such impairments in patients with ASD, including alterations in sensory systems. However, the cellular substrates and molecular underpinnings of disrupted connectivity remain poorly understood. Utilizing eye‐specific segregation in the dorsal lateral geniculate nucleus (dLGN) as a model system, we investigated the formation and refinement of precise patterning of synaptic connections in the BTBR T + tf/J (BTBR) mouse model of ASD. We found that at the neonatal stage, the shape of the dLGN occupied by retinal afferents was altered in the BTBR group compared to C57BL/6J (B6) animals. Notably, the degree of overlap between the ipsi‐ and contralateral afferents was significantly greater in the BTBR mice. Moreover, these abnormalities continued into mature stage in the BTBR animals, suggesting persistent deficits rather than delayed maturation of axonal refinement. Together, these results indicate disrupted connectivity at the synaptic patterning level in the BTBR mice, suggesting that in general, altered neural circuitry may contribute to autistic behaviours seen in this animal model. In addition, these data are consistent with the notion that lower‐level, primary processing mechanisms contribute to altered visual perception in ASD. Autism Res 2017, 10: 212–223. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
    August 16, 2016   doi: 10.1002/aur.1687   open full text
  • Sensory atypicalities in dyads of children with autism spectrum disorder (ASD) and their parents.
    Magdalena Glod, Deborah M. Riby, Emma Honey, Jacqui Rodgers.
    Autism Research. August 16, 2016
    Sensory atypicalities are a common feature of autism spectrum disorder (ASD). To date, the relationship between sensory atypicalities in dyads of children with ASD and their parents has not been investigated. Exploring these relationships can contribute to an understanding of how phenotypic profiles may be inherited, and the extent to which familial factors might contribute towards children's sensory profiles and constitute an aspect of the broader autism phenotype (BAP). Parents of 44 children with ASD and 30 typically developing (TD) children, aged between 3 and 14 years, participated. Information about children's sensory experiences was collected through parent report using the Sensory Profile questionnaire. Information about parental sensory experiences was collected via self‐report using the Adolescent/Adult Sensory Profile. Parents of children with ASD had significantly higher scores than parents of TD children in relation to low registration, over responsivity, and taste/smell sensory processing. Similar levels of agreement were obtained within ASD and TD parent‐child dyads on a number of sensory atypicalities; nevertheless significant correlations were found between parents and children in ASD families but not TD dyads for sensation avoiding and auditory, visual, and vestibular sensory processing. The findings suggest that there are similarities in sensory processing profiles between parents and their children in both ASD and TD dyads. Familial sensory processing factors are likely to contribute towards the BAP. Further work is needed to explore genetic and environmental influences on the developmental pathways of the sensory atypicalities in ASD. Autism Res 2017, 10: 531–538. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 16, 2016   doi: 10.1002/aur.1680   open full text
  • Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder.
    Richelle Mychasiuk, Jong M. Rho.
    Autism Research. August 16, 2016
    Background: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder characterized by hallmark behavioral features. The spectrum of disorders that fall within the ASD umbrella encompass a distinct but overlapping symptom complex that likely results from an array of molecular and genetic aberrations rather than a single genetic mutation. The ketogenic diet (KD) is a high‐fat low‐carbohydrate anti‐seizure and neuroprotective diet that has demonstrated efficacy in the treatment of ASD‐like behaviors in animal and human studies. Methods: We investigated changes in mRNA and gene expression in the BTBR mouse model of ASD that may contribute to the behavioral phenotype. In addition, we sought to examine changes in gene expression following KD treatment in BTBR mice. Results: Despite significant behavioral abnormalities, expression changes in BTBR mice did not differ substantially from controls; only 33 genes were differentially expressed in the temporal cortex, and 48 in the hippocampus. Examination of these differentially expressed genes suggested deficits in the stress response and in neuronal signaling/communication. After treatment with the KD, both brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development. Conclusions: Although our study supports many of the previously known impairments associated with ASD, such as excessive myelin formation and impaired GABAergic transmission, the RNAseq data and pathway analysis utilized here identified new therapeutic targets for analysis, such as Vitamin D pathways and cAMP signaling. Autism Res 2017, 10: 456–471. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 16, 2016   doi: 10.1002/aur.1682   open full text
  • RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex‐specific effects.
    Daniel S. Tylee, Alfred J. Espinoza, Jonathan L. Hess, Muhammad A. Tahir, Sarah Y. McCoy, Joshua K. Rim, Totadri Dhimal, Ori S. Cohen, Stephen J. Glatt.
    Autism Research. August 16, 2016
    Genome‐wide expression studies of samples derived from individuals with autism spectrum disorder (ASD) and their unaffected siblings have been widely used to shed light on transcriptomic differences associated with this condition. Females have historically been under‐represented in ASD genomic studies. Emerging evidence from studies of structural genetic variants and peripheral biomarkers suggest that sex‐differences may exist in the biological correlates of ASD. Relatively few studies have explicitly examined whether sex‐differences exist in the transcriptomic signature of ASD. The present study quantified genome‐wide expression values by performing RNA sequencing on transformed lymphoblastoid cell lines and identified transcripts differentially expressed between same‐sex, proximal‐aged sibling pairs. We found that performing separate analyses for each sex improved our ability to detect ASD‐related transcriptomic differences; we observed a larger number of dysregulated genes within our smaller set of female samples (n = 12 sibling pairs), as compared with the set of male samples (n = 24 sibling pairs), with small, but statistically significant overlap between the sexes. Permutation‐based gene‐set analyses and weighted gene co‐expression network analyses also supported the idea that the transcriptomic signature of ASD may differ between males and females. We discuss our findings in the context of the relevant literature, underscoring the need for future ASD studies to explicitly account for differences between the sexes. Autism Res 2017, 10: 439–455. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 16, 2016   doi: 10.1002/aur.1679   open full text
  • Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation, and child autistic traits: The moderating role of OXTR rs53576 genotype.
    Jolien Rijlaarsdam, Marinus H. van IJzendoorn, Frank C. Verhulst, Vincent W. V. Jaddoe, Janine F. Felix, Henning Tiemeier, Marian J. Bakermans‐Kranenburg.
    Autism Research. August 13, 2016
    Findings of studies investigating OXTR SNP rs53576 (G‐A) variation in social behavior have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. Our goal was to examine OXTR rs53576 allele‐specific sensitivity for neonatal OXTR DNA methylation in relation to (1) a prenatal maternal stress composite, and (2) child autistic traits. Prospective data from fetal life to age 6 years were collected in a total of 743 children participating in the Generation R Study. Prenatal maternal stress exposure was uniquely associated with child autistic traits but was unrelated to OXTR methylation across both OXTR rs53576 G‐allele homozygous children and A‐allele carriers. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction in the absence of main effects, suggesting that opposing effects cancelled each other out. Indeed, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G‐allele homozygous children but not for A‐allele carriers. These results highlight the importance of incorporating epi‐allelic information and support the role of OXTR methylation in child autistic traits. Autism Res 2017, 10: 430–438. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 13, 2016   doi: 10.1002/aur.1681   open full text
  • Neuron density is decreased in the prefrontal cortex in Williams syndrome.
    Caroline Horton Lew, Chelsea Brown, Ursula Bellugi, Katerina Semendeferi.
    Autism Research. August 13, 2016
    Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. Autism Res 2017, 10: 99–112. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 13, 2016   doi: 10.1002/aur.1677   open full text
  • “Is voice a marker for Autism spectrum disorder? A systematic review and meta‐analysis”.
    Riccardo Fusaroli, Anna Lambrechts, Dan Bang, Dermot M. Bowler, Sebastian B. Gaigg.
    Autism Research. August 08, 2016
    Individuals with Autism Spectrum Disorder (ASD) tend to show distinctive, atypical acoustic patterns of speech. These behaviors affect social interactions and social development and could represent a non‐invasive marker for ASD. We systematically reviewed the literature quantifying acoustic patterns in ASD. Search terms were: (prosody OR intonation OR inflection OR intensity OR pitch OR fundamental frequency OR speech rate OR voice quality OR acoustic) AND (autis* OR Asperger). Results were filtered to include only: empirical studies quantifying acoustic features of vocal production in ASD, with a sample size >2, and the inclusion of a neurotypical comparison group and/or correlations between acoustic measures and severity of clinical features. We identified 34 articles, including 30 univariate studies and 15 multivariate machine‐learning studies. We performed meta‐analyses of the univariate studies, identifying significant differences in mean pitch and pitch range between individuals with ASD and comparison participants (Cohen's d of 0.4–0.5 and discriminatory accuracy of about 61–64%). The multivariate studies reported higher accuracies than the univariate studies (63–96%). However, the methods used and the acoustic features investigated were too diverse for performing meta‐analysis. We conclude that multivariate studies of acoustic patterns are a promising but yet unsystematic avenue for establishing ASD markers. We outline three recommendations for future studies: open data, open methods, and theory‐driven research. Autism Res 2017, 10: 384–407. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 08, 2016   doi: 10.1002/aur.1678   open full text
  • Novel Shank3 mutant exhibits behaviors with face validity for autism and altered striatal and hippocampal function.
    Thomas C. Jaramillo, Haley E. Speed, Zhong Xuan, Jeremy M. Reimers, Christine Ochoa Escamilla, Travis P. Weaver, Shunan Liu, Irina Filonova, Craig M. Powell.
    Autism Research. August 05, 2016
    Mutations/deletions in the SHANK3 gene are associated with autism spectrum disorders and intellectual disability. Here, we present electrophysiological and behavioral consequences in novel heterozygous and homozygous mice with a transcriptional stop cassette inserted upstream of the PDZ domain‐coding exons in Shank3 (Shank3E13). Insertion of a transcriptional stop cassette prior to exon 13 leads to loss of the two higher molecular weight isoforms of Shank3. Behaviorally, both Shank3E13 heterozygous (HET) and homozygous knockout (KO) mice display increased repetitive grooming, deficits in social interaction tasks, and decreased rearing. Shank3E13 KO mice also display deficits in spatial memory in the Morris water maze task. Baseline hippocampal synaptic transmission and short‐term plasticity are preserved in Shank3E13 HET and KO mice, while both HET and KO mice exhibit impaired hippocampal long‐term plasticity. Additionally, Shank3E13 HET and KO mice display impaired striatal glutamatergic synaptic transmission. These results demonstrate for the first time in this novel Shank3 mutant that both homozygous and heterozygous mutation of Shank3 lead to behavioral abnormalities with face validity for autism along with widespread synaptic dysfunction. Autism Res 2017, 10: 42–65. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 05, 2016   doi: 10.1002/aur.1664   open full text
  • Development and validation of a streamlined autism case confirmation approach for use in epidemiologic risk factor research in prospective cohorts.
    Craig J. Newschaffer, Emily Schriver, Lindsay Berrigan, Rebecca Landa, Wendy L. Stone, Somer Bishop, Diane Burkom, Anne Golden, Lisa Ibanez, Alice Kuo, Kimberly D. Lakes, Daniel S. Messinger, Sarah Paterson, Zachary E. Warren.
    Autism Research. August 03, 2016
    The cost associated with incorporating standardized observational assessments and diagnostic interviews in large‐scale epidemiologic studies of autism spectrum disorders (ASD) risk factors can be substantial. Streamlined approaches for confirming ASD case status would benefit these studies. We conducted a multi‐site, cross‐sectional criterion validity study in a convenience sample of 382 three‐year olds scheduled for neurodevelopmental evaluation. ASD case classification as determined by three novel assessment instruments (the Early Video‐guided Autism Screener E‐VAS; the Autism Symptom Interview, ASI; the Screening Tool for Autism in Toddlers Expanded, STAT‐E) each designed to be administered in less than 30 minutes by lay staff, was compared to ADOS scores and DSM‐based diagnostic assessment from a qualified clinician. Sensitivity and specificity of each instrument alone and in combination were estimated. Alternative cutpoints were identified under different criteria and two‐stage cross validation was used to avoid overfitting. Findings were interpreted in the context of a large, prospective pregnancy cohort study utilizing a two‐stage approach to case identification. Under initial cutpoints, sensitivity ranged from 0.63 to 0.92 and specificity from 0.35 to 0.70. Cutpoints giving equal weight to sensitivity and specificity resulted in sensitivity estimates ranging from 0.45 to 0.83 and specificity ranging from 0.49 to 0.86. Several strategies were well‐suited for application as a second‐stage case‐confirmation. These included the STAT‐E alone and the parallel administration of both the E‐VAS and the ASI. Use of more streamlined methods of case‐confirmation in large‐scale prospective cohort epidemiologic investigations of ASD risk factors appears feasible. Autism Res 2017, 10: 485–501. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 03, 2016   doi: 10.1002/aur.1659   open full text
  • Context processing in adolescents with autism spectrum disorder: How complex could it be?
    Dekel Ben‐Yosef, David Anaki, Ofer Golan.
    Autism Research. August 03, 2016
    The ability of individuals with Autism Spectrum Disorder (ASD) to process context has long been debated: According to the Weak Central Coherence theory, ASD is characterized by poor global processing, and consequently—poor context processing. In contrast, the Social Cognition theory argues individuals with ASD will present difficulties only in social context processing. The complexity theory of autism suggests context processing in ASD will depend on task complexity. The current study examined this controversy through two priming tasks, one presenting human stimuli (facial expressions) and the other presenting non‐human stimuli (animal faces). Both tasks presented visual targets, preceded by congruent, incongruent, or neutral auditory primes. Local and global processing were examined by presenting the visual targets in three spatial frequency conditions: High frequency, low frequency, and broadband. Tasks were administered to 16 adolescents with high functioning ASD and 16 matched typically developing adolescents. Reaction time and accuracy were measured for each task in each condition. Results indicated that individuals with ASD processed context for both human and non‐human stimuli, except in one condition, in which human stimuli had to be processed globally (i.e., target presented in low frequency). The task demands presented in this condition, and the performance deficit shown in the ASD group as a result, could be understood in terms of cognitive overload. These findings provide support for the complexity theory of autism and extend it. Our results also demonstrate how associative priming could support intact context processing of human and non‐human stimuli in individuals with ASD. Autism Res 2017, 10: 520–530. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 03, 2016   doi: 10.1002/aur.1676   open full text
  • Serotonin neuron abnormalities in the BTBR mouse model of autism.
    Yue‐Ping Guo, Kathryn G. Commons.
    Autism Research. August 01, 2016
    The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) is studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region‐dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. Autism Res 2017, 10: 66–77. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    August 01, 2016   doi: 10.1002/aur.1665   open full text
  • The stability and validity of automated vocal analysis in preverbal preschoolers with autism spectrum disorder.
    Tiffany Woynaroski, D. Kimbrough Oller, Bahar Keceli‐Kaysili, Dongxin Xu, Jeffrey A. Richards, Jill Gilkerson, Sharmistha Gray, Paul Yoder.
    Autism Research. July 26, 2016
    Theory and research suggest that vocal development predicts “useful speech” in preschoolers with autism spectrum disorder (ASD), but conventional methods for measurement of vocal development are costly and time consuming. This longitudinal correlational study examines the reliability and validity of several automated indices of vocalization development relative to an index derived from human coded, conventional communication samples in a sample of preverbal preschoolers with ASD. Automated indices of vocal development were derived using software that is presently “in development” and/or only available for research purposes and using commercially available Language ENvironment Analysis (LENA) software. Indices of vocal development that could be derived using the software available for research purposes: (a) were highly stable with a single day‐long audio recording, (b) predicted future spoken vocabulary to a degree that was nonsignificantly different from the index derived from conventional communication samples, and (c) continued to predict future spoken vocabulary even after controlling for concurrent vocabulary in our sample. The score derived from standard LENA software was similarly stable, but was not significantly correlated with future spoken vocabulary. Findings suggest that automated vocal analysis is a valid and reliable alternative to time intensive and expensive conventional communication samples for measurement of vocal development of preverbal preschoolers with ASD in research and clinical practice. Autism Res 2017, 10: 508–519. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 26, 2016   doi: 10.1002/aur.1667   open full text
  • SLC9A9 Co‐expression modules in autism‐associated brain regions.
    Jameson Patak, Jonathan L. Hess, Yanli Zhang‐James, Stephen J. Glatt, Stephen V. Faraone.
    Autism Research. July 21, 2016
    SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism‐associated brain regions throughout development. We conducted a weighted gene co‐expression network analysis on RNA‐seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD‐associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD‐associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co‐immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. Autism Res 2017, 10: 414–429. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 21, 2016   doi: 10.1002/aur.1670   open full text
  • High autistic trait individuals do not modulate gaze behaviour in response to social presence but look away more when actively engaged in an interaction.
    Elisabeth A. H. von dem Hagen, Naomi Bright.
    Autism Research. July 19, 2016
    Autism is characterised by difficulties in social functioning, notably in interactions with other people. Yet, most studies addressing social difficulties have used static images or, at best, videos of social stimuli, with no scope for real interaction. Here, we study one crucial aspect of social interactions—gaze behaviour—in an interactive setting. First, typical individuals were shown videos of an experimenter and, by means of a deception procedure, were either led to believe that the experimenter was present via a live video‐feed or was pre‐recorded. Participants' eye movements revealed that when passively viewing an experimenter they believed to be “live,” they looked less at that person than when they believed the experimenter video was pre‐recorded. Interestingly, this reduction in viewing behaviour in response to the believed “live” presence of the experimenter was absent in individuals high in autistic traits, suggesting a relative insensitivity to social presence alone. When participants were asked to actively engage in a real‐time interaction with the experimenter, however, high autistic trait individuals looked significantly less at the experimenter relative to low autistic trait individuals. The results reinforce findings of atypical gaze behaviour in individuals high in autistic traits, but suggest that active engagement in a social interaction may be important in eliciting reduced looking. We propose that difficulties with the spatio‐temporal dynamics associated with real social interactions rather than underlying difficulties processing the social stimulus itself may drive these effects. The results underline the importance of developing ecologically valid methods to investigate social cognition. Autism Res 2017, 10: 359–368. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
    July 19, 2016   doi: 10.1002/aur.1666   open full text
  • Non‐ASD outcomes at 36 months in siblings at familial risk for autism spectrum disorder (ASD): A baby siblings research consortium (BSRC) study.
    Tony Charman, Gregory S. Young, Jessica Brian, Alice Carter, Leslie J. Carver, Katarzyna Chawarska, Suzanne Curtin, Karen Dobkins, Mayada Elsabbagh, Stelios Georgiades, Irva Hertz‐Picciotto, Ted Hutman, Jana M. Iverson, Emily J. Jones, Rebecca Landa, Suzanne Macari, Daniel S. Messinger, Charles A. Nelson, Sally Ozonoff, Celine Saulnier, Wendy L. Stone, Helen Tager‐Flusberg, Sara Jane Webb, Nurit Yirmiya, Lonnie Zwaigenbaum.
    Autism Research. July 15, 2016
    We characterized developmental outcomes of a large sample of siblings at familial high‐risk of autism spectrum disorder (ASD), who themselves did not have ASD (n = 859), and low‐risk controls with no family history of ASD (n = 473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview—Revised (ADI‐R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high‐risk siblings had mild‐to‐moderate levels of developmental delay, a rate higher than the low‐risk controls. The groups did not differ in the proportion of toddlers with mild‐to‐moderate language delay. Thirty percent of high‐risk siblings had elevated scores on the ADOS, double the rate seen in the low‐risk controls. High‐risk siblings also had higher parent reported levels of ASD symptoms on the ADI‐R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild‐to‐moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the “broader autism phenotype” (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high‐risk siblings who do not have an ASD by age 3 years, as well as continued follow‐up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169–178. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 15, 2016   doi: 10.1002/aur.1669   open full text
  • Salivary cortisol and behavioral response to social evaluative threat in adolescents with autism spectrum disorder.
    E. Kale Edmiston, Scott D. Blain, Blythe A. Corbett.
    Autism Research. July 15, 2016
    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behavior. One possible explanation for social communication deficits in ASD could be differences in biological systems that support responses to environmental stimuli. If so, it is unclear if differences in the arousal response to social stimuli in ASD are due to reduced interest in social information, or to an increased stress response. The hypothalamic pituitary adrenal axis facilitates arousal and the stress response to sensory input, including social stimuli. Previous research shows blunted cortisol response to social evaluative threat in children with ASD. The majority of prior work has focused on children with ASD, but adolescents with ASD are understudied. The adolescent period is of interest, as this developmental epoch is associated with increased salience of social evaluative threat in typically developing (TD) populations. In this study, we employed the Trier Social Stress Test (TSST), a laboratory paradigm that involves exposure to social evaluative threat, to study the cortisol and behavioral response to social evaluative threat in ASD and TD adolescents. Salivary cortisol data were collected at six time points before and after the TSST. Behavioral data were collected using video recordings of the TSST, which were then operationalized and coded. Paired sample t‐tests were used to calculate within‐group cortisol response to the TSST. Cortisol significantly increased in response to the TSST in the TD group but not the ASD group. The TD group showed a trend for more self‐soothing behaviors during the stressor than the ASD group. The lack of a cortisol response to the TSST in the ASD group suggests that the TSST is not interpreted as stressful or salient for ASD adolescents. Autism Res 2017, 10: 346–358. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 15, 2016   doi: 10.1002/aur.1660   open full text
  • Lack of replication of previous autism spectrum disorder GWAS hits in European populations.
    Bàrbara Torrico, Andreas G. Chiocchetti, Elena Bacchelli, Elisabetta Trabetti, Amaia Hervás, Barbara Franke, Jan K. Buitelaar, Nanda Rommelse, Afsheen Yousaf, Eftichia Duketis, Christine M. Freitag, Rafaela Caballero‐Andaluz, Amalia Martinez‐Mir, Francisco G. Scholl, Marta Ribasés, , Agatino Battaglia, Giovanni Malerba, Richard Delorme, Marion Benabou, Elena Maestrini, Thomas Bourgeron, Bru Cormand, Claudio Toma.
    Autism Research. July 15, 2016
    Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome‐wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family‐based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case‐control association study in five European populations of ASD patients and gender‐matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta‐analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI = 0.84–1.32) for rs10513025, 1.0002 (95% CI = 0.93–1.08) for rs4141463 and 1.01 (95% CI = 0.92–1.1) for rs4307059, with no significant P‐values (rs10513025, P = 0.73; rs4141463, P = 0.95; rs4307059, P = 0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. Autism Res 2017, 10: 202–211. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 15, 2016   doi: 10.1002/aur.1662   open full text
  • Children with autism spectrum disorder have reduced otoacoustic emissions at the 1 kHz mid‐frequency region.
    Loisa Bennetto, Jessica M. Keith, Paul D. Allen, Anne E. Luebke.
    Autism Research. July 12, 2016
    Autism spectrum disorder (ASD) is a behaviorally diagnosed disorder of early onset characterized by impairment in social communication and restricted and repetitive behaviors. Some of the earliest signs of ASD involve auditory processing, and a recent study found that hearing thresholds in children with ASD in the mid‐range frequencies were significantly related to receptive and expressive language measures. In addition, otoacoustic emissions have been used to detect reduced cochlear function in the presence of normal audiometric thresholds. We were interested then to know if otoacoustic emissions in children with normal audiometric thresholds would also reveal differences between children with ASD and typical developing (TD) controls in mid‐frequency regions. Our objective was to specifically measure baseline afferent otoacoustic emissions (distortion‐product otoacoustic emissions [DPOAEs]), transient‐evoked otoacoustic emissions (TrOAEs), and efferent suppression, in 35 children with high‐functioning ASD compared with 42 aged‐matched TD controls. All participants were males 6–17 years old, with normal audiometry, and rigorously characterized via Autism Diagnostic Interview‐Revised and Autism Diagnostic Observation Schedule. Children with ASD had greatly reduced DPOAE responses in the 1 kHz frequency range, yet had comparable DPOAE responses at 0.5 and 4–8 kHz regions. Furthermore, analysis of the spectral features of TrOAEs revealed significantly decreased emissions in ASD in similar frequencies. No significant differences were noted in DPOAE or TrOAE noise floors, middle ear muscle reflex activity, or efferent suppression between children with ASD and TD controls. In conclusion, attention to specific‐frequency deficits using non‐invasive measures of cochlear function may be important in auditory processing impairments found in ASD. Autism Res 2017, 10: 337–345. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 12, 2016   doi: 10.1002/aur.1663   open full text
  • Voice identity processing in autism spectrum disorder.
    Stefanie Schelinski, Claudia Roswandowitz, Katharina von Kriegstein.
    Autism Research. July 12, 2016
    People with autism spectrum disorder (ASD) have difficulties in identifying another person by face and voice. This might contribute considerably to the development of social cognition and interaction difficulties. The characteristics of the voice recognition deficit in ASD are unknown. Here, we used a comprehensive behavioral test battery to systematically investigate voice processing in high‐functioning ASD (n = 16) and typically developed pair‐wise matched controls (n = 16). The ASD group had particular difficulties with discriminating, learning, and recognizing unfamiliar voices, while recognizing famous voices was relatively intact. Tests on acoustic processing abilities showed that the ASD group had a specific deficit in vocal pitch perception that was dissociable from otherwise intact acoustic processing (i.e., musical pitch, musical, and vocal timbre perception). Our results allow a characterization of the voice recognition deficit in ASD: The findings indicate that in high‐functioning ASD, the difficulty to recognize voices is particularly pronounced for learning novel voices and the recognition of unfamiliar peoples’ voices. This pattern might be indicative of difficulties with integrating the acoustic characteristics of the voice into a coherent percept—a function that has been previously associated with voice‐selective regions in the posterior superior temporal sulcus/gyrus of the human brain. Autism Res 2017, 10: 155–168. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 12, 2016   doi: 10.1002/aur.1639   open full text
  • Category structure and processing in 6‐year‐old children with autism.
    Allison Bean Ellawadi, Deborah Fein, Letitia R. Naigles.
    Autism Research. July 12, 2016
    This study investigated the categorization abilities of 6‐year‐old children with autism spectrum disorders (ASD) as compared to their peers with typical development (TD) using a category verification task. We examined the impact of stimulus typicality on multiple aspects of real‐time performance, including accuracy, reaction time, and performance stability. Both groups were more accurate in identifying typical category members than atypical ones; however, only the ASD group's accuracy was affected by item ordering, indicating less stable performance. Furthermore, category structure was predicted by concurrent language levels in the TD group but by concurrent nonverbal IQ in the ASD group; these latter two findings suggest that children with ASD process categories differently than their peers with TD. Autism Res 2017, 10: 327–336. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 12, 2016   doi: 10.1002/aur.1652   open full text
  • Threatening faces fail to guide attention for adults with autistic‐like traits.
    Michael C. W. English, Murray T. Maybery, Troy A. W. Visser.
    Autism Research. July 07, 2016
    Individuals diagnosed with autistic spectrum conditions often show deficits in processing emotional faces relative to neurotypical peers. However, little is known about whether similar deficits exist in neurotypical individuals who show high‐levels of autistic‐like traits. To address this question, we compared performance on an attentional blink task in a large sample of adults who showed low‐ or high‐levels of autistic‐like traits on the Autism Spectrum Quotient. We found that threatening faces inserted as the second target in a rapid serial visual presentation were identified more accurately among individuals with low‐ compared to high‐levels of autistic‐like traits. This is the first study to show that attentional blink abnormalities seen in autism extend to the neurotypical population with autistic‐like traits, adding to the growing body of research suggesting that autistic‐related patterns of behaviors extend into a subset of the neurotypical population. Autism Res 2017, 10: 311–320. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 07, 2016   doi: 10.1002/aur.1658   open full text
  • Heterogeneity of subclinical autistic traits among parents of children with autism spectrum disorder: Identifying the broader autism phenotype with a data‐driven method.
    Emre Bora, Aydan Aydın, Tuğba Saraç, Muhammed Tayyib Kadak, Sezen Köse.
    Autism Research. July 07, 2016
    Clinical diagnosis of autism spectrum disorder (ASD) can be conceptualized as the extreme end of the distribution of subclinical autistic traits related to genetic susceptibility factors (broad autism phenotype (BAP)) in the general population. Subclinical autistic traits are significantly more common among unaffected first‐degree relatives of probands with autism. However, there is a significant heterogeneity of autistic traits in family members of individuals with ASD and severity of autistic traits are not significantly different from controls in the majority of these relatives. The current study investigated the heterogeneity of autistic traits using latent class analysis (LCA) of the Autism Spectrum Quotient (AQ) ratings of 673 parents of children with ASD and 147 parents of typically developing children. Two distinct subgroups, including a "low‐scoring" and a "high‐scorer (BAP)" groups, were found. In comparison to control parents, a significantly larger proportion (21.1% vs. 7.5%) of parents of ASD were members of BAP group. Communication subscale made a distinctive contribution to the separation of high and low‐scoring groups (d = 2.77). Further studies investigating neurobiological and genetic biomarkers and stability of these two subgroups over time are important for understanding the nature of autistic traits in the general population. Autism Res 2017, 10: 321–326. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    July 07, 2016   doi: 10.1002/aur.1661   open full text
  • Intact mirror mechanisms for automatic facial emotions in children and adolescents with autism spectrum disorder.
    Martin Schulte‐Rüther, Ellen Otte, Kübra Adigüzel, Christine Firk, Beate Herpertz‐Dahlmann, Iring Koch, Kerstin Konrad.
    Autism Research. June 28, 2016
    It has been suggested that an early deficit in the human mirror neuron system (MNS) is an important feature of autism. Recent findings related to simple hand and finger movements do not support a general dysfunction of the MNS in autism. Studies investigating facial actions (e.g., emotional expressions) have been more consistent, however, mostly relied on passive observation tasks. We used a new variant of a compatibility task for the assessment of automatic facial mimicry responses that allowed for simultaneous control of attention to facial stimuli. We used facial electromyography in 18 children and adolescents with Autism spectrum disorder (ASD) and 18 typically developing controls (TDCs). We observed a robust compatibility effect in ASD, that is, the execution of a facial expression was facilitated if a congruent facial expression was observed. Time course analysis of RT distributions and comparison to a classic compatibility task (symbolic Simon task) revealed that the facial compatibility effect appeared early and increased with time, suggesting fast and sustained activation of motor codes during observation of facial expressions. We observed a negative correlation of the compatibility effect with age across participants and in ASD, and a positive correlation between self‐rated empathy and congruency for smiling faces in TDC but not in ASD. This pattern of results suggests that basic motor mimicry is intact in ASD, but is not associated with complex social cognitive abilities such as emotion understanding and empathy. Autism Res 2017, 10: 298–310. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    June 28, 2016   doi: 10.1002/aur.1654   open full text
  • The Autism‐Spectrum Quotient in Siblings of People With Autism.
    Emily Ruzich, Carrie Allison, Paula Smith, Howard Ring, Bonnie Auyeung, Simon Baron‐Cohen.
    Autism Research. June 22, 2016
    This study measures the distribution of autistic traits, using the autism‐spectrum quotient (AQ), in siblings of individuals with autism spectrum conditions (ASC). Total AQ scores, along with AQ subscales, were collected from child, adolescent and adult controls, siblings, and volunteers with ASC using one of the three age‐appropriate versions of the instrument: the AQ (adult self‐report), the AQ‐adolescent and AQ‐child (both parent‐reports). We examined the effect of Group (case, sibling and control) and AQ version (adult, adolescent and adult) on total and subscale scores. In addition, we tested for sex differences in all groups and on all versions. We found that in male and female adults, AQ scores in siblings fell between cases and controls (cases > siblings > controls). In children and adolescents, female siblings also scored higher than control females (female cases > female siblings > female controls), but there was no difference between male siblings and controls (male cases > male siblings = male controls). An investigation of subscale scores revealed that male siblings only differed from controls on the “Communication” subscale (male cases > male siblings > male controls), while female siblings differed from controls on all subscales except “Imagination” (female cases > female siblings > female controls). This study confirms the broader autism phenotype in siblings, and reveals this is modulated by sex and AQ version. Autism Res 2017, 10: 289–297. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
    June 22, 2016   doi: 10.1002/aur.1651   open full text
  • Psychophysiological Associations with Gastrointestinal Symptomatology in Autism Spectrum Disorder.
    Bradley J. Ferguson, Sarah Marler, Lily L. Altstein, Evon Batey Lee, Jill Akers, Kristin Sohl, Aaron McLaughlin, Kaitlyn Hartnett, Briana Kille, Micah Mazurek, Eric A. Macklin, Erin McDonnell, Mariah Barstow, Margaret L. Bauman, Kara Gross Margolis, Jeremy Veenstra‐VanderWeele, David Q. Beversdorf.
    Autism Research. June 20, 2016
    Autism spectrum disorder (ASD) is often accompanied by gastrointestinal disturbances, which also may impact behavior. Alterations in autonomic nervous system functioning are also frequently observed in ASD. The relationship between these findings in ASD is not known. We examined the relationship between gastrointestinal symptomatology, examining upper and lower gastrointestinal tract symptomatology separately, and autonomic nervous system functioning, as assessed by heart rate variability and skin conductance level, in a sample of 120 individuals with ASD. Relationships with co‐occurring medical and psychiatric symptoms were also examined. While the number of participants with significant upper gastrointestinal tract problems was small in this sample, 42.5% of participants met criteria for functional constipation, a disorder of the lower gastrointestinal tract. Heart rate variability, a measure of parasympathetic modulation of cardiac activity, was found to be positively associated with lower gastrointestinal tract symptomatology at baseline. This relationship was particularly strong for participants with co‐occurring diagnoses of anxiety disorder and for those with a history of regressive ASD or loss of previously acquired skills. These findings suggest that autonomic function and gastrointestinal problems are intertwined in children with ASD; although it is not possible to assess causality in this data set. Future work should examine the impact of treatment of gastrointestinal problems on autonomic function and anxiety, as well as the impact of anxiety treatment on gastrointestinal problems. Clinicians should be aware that gastrointestinal problems, anxiety, and autonomic dysfunction may cluster in children with ASD and should be addressed in a multidisciplinary treatment plan. Autism Res 2017, 10: 276–288. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    June 20, 2016   doi: 10.1002/aur.1646   open full text
  • Autism‐specific maternal anti‐fetal brain autoantibodies are associated with metabolic conditions.
    Paula Krakowiak, Cheryl K. Walker, Daniel Tancredi, Irva Hertz‐Picciotto, Judy Van de Water.
    Autism Research. June 17, 2016
    Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of autoantibodies to fetal brain proteins that have been detected in only 1% of mothers of typically developing children. The biological mechanisms underlying the development of ASD‐specific maternal autoantibodies are poorly understood. We sought to determine whether ASD‐specific maternal autoantibodies identified postnatally were associated with metabolic conditions (MCs) during gestation. Participants were 227 mothers of 2–5 year old children with confirmed ASD, enrolled in CHARGE (Childhood Autism Risk from Genetics and the Environment) between January 2003 and April 2008, and from whom blood samples were collected and analyzed for anti‐fetal brain autoantibodies (Ab+). MCs included diabetes, hypertensive disorders, and prepregnancy obesity or overweight, ascertained from medical records or structured telephone interviews. Log‐linear regression models were performed to estimate prevalence ratios and 95% confidence intervals (CI) based on robust standard errors. Fifty‐six (25%) mothers were Ab+. Ab+ prevalence was higher among mothers with diabetes, hypertensive disorders, or overweight compared to healthy mothers, but differences were not statistically significant. In a subset of 145 mothers whose children exhibited severe ASD (31 Ab+), those diagnosed with type 2 or gestational diabetes were 2.7‐fold more likely to be Ab+ (95% CI 1.1, 6.6), controlling for delivery payer and smoking. Gestational diabetes specifically was associated with a 3.2‐fold increased Ab+ prevalence (95% CI 1.2, 8.6). In this exploratory study, mothers whose children had severe ASD and who experienced diabetes were more likely to have anti‐fetal brain autoantibodies 2–5 years later. Autism Res 2017, 10: 89–98. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    June 17, 2016   doi: 10.1002/aur.1657   open full text
  • Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case–control study.
    Rezvan Noroozi, Mohammad Taheri, Abolfazl Movafagh, Reza Mirfakhraie, Ghasem Solgi, Arezou Sayad, Mehrdokht Mazdeh, Hossein Darvish.
    Autism Research. June 17, 2016
    Autism spectrum disorder (ASD) as a synaptopathy is revealed to be pertained to aberrant glutamatergic neurotransmission. Glutamate receptor, metabotropic 7 (GRM7), a receptor coding gene of this pathway, is a new candidate gene for autism. The aim of this study was to examine if there is a relationship between genetic variants rs779867 and rs6782011 of GRM7 with ASD. The present research was designed as a population‐based, case–control study including 518 ASD patients versus 472 control individuals. The results showed that the frequency of rs779867 G/G genotype was significantly higher in ASD patients compared to healthy controls (P = 0.0001). Also, the G allele of this SNP was found to be significantly more frequent in the patients than control group (P = 0.0001). Haplotype analysis exhibited significant association of two estimated block of rs6782011/rs779867 in ASD patients versus control group. We found higher significant frequency of GT haplotype and lower frequencies of AT and AC haplotypes in the patients group compared to healthy controls (P = 0.001, P = 0.006, and P = 0.05, respectively). Our study indicated that the rs779867 polymorphism is associated with ASD; thus, results of this study provide supportive evidence of association of the GRM7 gene with ASD. Autism Res 2016, 9: 1161–1168. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    June 17, 2016   doi: 10.1002/aur.1640   open full text
  • Linkage between pain sensitivity and empathic response in adolescents with autism spectrum conditions and conduct disorder symptoms.
    Chenyi Chen, An‐Yi Hung, Yang‐Teng Fan, Shuai Tan, Hua Hong, Yawei Cheng.
    Autism Research. June 16, 2016
    Lack of empathy is one of the behavioral hallmarks in individuals with autism spectrum conditions (ASC) as well as youth with conduct disorder symptoms (CDS). Previous research has reliably documented considerable overlap between the perception of others' pain and first‐hand experience of pain. However, the linkage between empathy for pain and sensitivity to physical pain needs to be empirically determined, particularly in individuals with empathy deficits. This study measured the pressure pain threshold, which indexes sensitization of peripheral nociceptors, and assessed subjective ratings of unpleasantness and pain intensity in response to empathy‐eliciting stimuli depicting physical bodily injuries in three age‐ and sex‐matched participant groups: ASC, CDS, and typically developing controls (TDC). The results indicated that the pain threshold was lowest in the ASC group and highest in the CDS group. The ASC group displayed lower ratings of unpleasantness and pain intensity than did the TDC and CDS groups. Within the ASC and CDS, pain intensity ratings were significantly correlated with unpleasantness ratings to others' pain. Moreover, the ASC significantly differed from the TDC in the correlation between pain threshold values and unpleasantness ratings. These findings may cast some light on the linkage between atypical low‐level sensory functioning, for instance altered pain sensitivity, and high‐level empathic processing. Autism Res 2017, 10: 267–275. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    June 16, 2016   doi: 10.1002/aur.1653   open full text
  • The autism symptom interview, school‐age: A brief telephone interview to identify autism spectrum disorders in 5‐to‐12‐year‐old children.
    Somer L. Bishop, Marisela Huerta, Katherine Gotham, Karoline Alexandra Havdahl, Andrew Pickles, Amie Duncan, Vanessa Hus Bal, Lisa Croen, Catherine Lord.
    Autism Research. June 10, 2016
    This study reports on the initial validation of the Autism Symptom Interview (ASI), School‐Age, a brief (15–20 min) phone interview derived from questions from the Autism Diagnostic Interview‐Revised (ADI‐R). The ASI, School‐Age was administered by interviewers with minimal training to parents of children ages 5 to 12 who had all been previously identified with (or referred for assessment of) ASD or another neurodevelopmental disorder. Children then underwent a comprehensive assessment to determine a best‐estimate clinical diagnosis of ASD (n = 159) or non‐ASD (e.g. language disorder, intellectual disability, ADHD; n = 130). Clinicians who conducted the assessments were blind to ASI results. ROC analyses compared ASI scores to clinical diagnosis. Due to the small number of participants with non‐ASD diagnoses who were classified as nonverbal (i.e. not yet using phrases on a daily basis), it was not possible to assess sensitivity and specificity of the nonverbal algorithm in this sample. The verbal algorithm yielded a sensitivity of 0.87 (95% CI = 0.81–0.92) and a specificity of 0.62 (95% CI = 0.53–0.70). When used in conjunction with the Autism Diagnostic Observation Schedule (ADOS), sensitivity and specificity were 0.82 (95% CI = 0.74–0.88) and 0.92 (95% CI = 0.86–0.96), respectively. Internal consistency and test‐retest reliability were both excellent. Particularly for verbal school age children, the ASI may serve as a useful tool to more quickly ascertain or classify children with ASD for research or clinical triaging purposes. Additional data collection is underway to determine the utility of the ASI in children who are younger and/or nonverbal. Autism Res 2017, 10: 78–88. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    June 10, 2016   doi: 10.1002/aur.1645   open full text
  • Persistence of megalencephaly in a subgroup of young boys with autism spectrum disorder.
    Lauren E. Libero, Christine W. Nordahl, Deana D. Li, Emilio Ferrer, Sally J. Rogers, David G. Amaral.
    Autism Research. June 08, 2016
    A recurring finding in autism spectrum disorder research is that head and brain growth is disproportionate to body growth in early childhood. Nordahl et al. (2011) demonstrated that this occurs in approximately 15% of boys with autism. While the literature suggests that brain growth normalizes at older ages, this has never been evaluated in a longitudinal study. The current study evaluated head circumference and total cerebral volume in 129 male children with autism and 49 age‐matched, typically developing controls. We determined whether 3‐year‐old boys with brain size disproportionate to height (which we call disproportionate megalencephaly) demonstrated an abnormal trajectory of head growth from birth and whether they maintained an enlarged brain at 5 years of age. Findings were based on longitudinal, structural MRI data collected around 3, 4, and 5 years of age and head circumference data from medical records. At 3 years of age, 19 boys with autism had enlarged brains while 110 had brain sizes in the normal range. Boys with disproportionate megalencephaly had greater total cerebral, gray matter, and white matter volumes from 3–5 years compared to boys with autism and normal sized brains and typically developing boys, but no differences in body size. While head circumference did not differ between groups at birth, it was significantly greater in the disproportionate megalencephaly group by around 2 years. These data suggest that there is a subgroup of boys with autism who have brains disproportionate to body size and that this continues until at least 5 years of age. Autism Res 2016, 9: 1169–1182. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    June 08, 2016   doi: 10.1002/aur.1643   open full text
  • Vestibulo‐ocular reflex function in children with high‐functioning autism spectrum disorders.
    Tana B. Carson, Bradley J. Wilkes, Kunal Patel, Jill L. Pineda, Ji H. Ko, Karl M. Newell, James W. Bodfish, Michael C. Schubert, Krestin Radonovich, Keith D. White, Mark H. Lewis.
    Autism Research. May 25, 2016
    Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism Spectrum Disorders (ASD). The rotational vestibulo‐ocular reflex (rVOR), which functions to maintain stable vision during head movements, is a sensorimotor system that may be useful in understanding such alterations and their underlying neurobiology. In this study, we assessed post‐rotary nystagmus elicited by continuous whole body rotation among children with high‐functioning ASD and typically developing children. Children with ASD exhibited increased rVOR gain, the ratio of eye velocity to head velocity, indicating a possible lack of cerebellar inhibitory input to brainstem vestibular nuclei in this population. The ASD group also showed less regular or periodic horizontal eye movements as indexed by greater variance accounted for by multiple higher frequency bandwidths as well as greater entropy scores compared to typically developing children. The decreased regularity or dysrhythmia in the temporal structure of nystagmus beats in children with ASD may be due to alterations in cerebellum and brainstem circuitry. These findings could potentially serve as a model to better understand the functional effects of differences in these brain structures in ASD. Autism Res 2017, 10: 251–266. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 25, 2016   doi: 10.1002/aur.1642   open full text
  • Autism‐relevant behaviors are minimally impacted by conditional deletion of Pten in oxytocinergic neurons.
    Amy E. Clipperton‐Allen, Youjun Chen, Damon T. Page.
    Autism Research. May 25, 2016
    Germline heterozygous mutations in Pten (phosphatase and tensin homolog) are associated with macrocephaly and autism spectrum disorders (ASD). Pten germline heterozygous (Pten+/−) mice approximate these mutations, and both sexes show widespread brain overgrowth and impaired social behavior. Strikingly similar behavior phenotypes have been reported in oxytocin (Oxt) and/or oxytocin receptor (OxtR) knockout mice. Thus, we hypothesized that the behavioral phenotypes of germline Pten+/− mice may be caused by reduced Pten function in Oxt‐expressing cells. To investigate this, we tested mice in which Pten was conditionally deleted using oxytocin‐Cre (Oxt‐Cre+; PtenloxP/+, Oxt‐Cre+; PtenloxP/loxP) on a battery including assays of social, repetitive, depression‐like, and anxiety‐like behaviors. Minimal behavioral abnormalities were found; decreased anxiety‐like behavior in the open field test in Oxt‐Cre+; PtenloxP/loxP males was the only result that phenocopied germline Pten+/− mice. However, Oxt cell size was dramatically increased in Oxt‐Cre+; PtenloxP/loxP mice in adulthood. Thus, conditional deletion of Pten using Oxt‐Cre has a profound effect on Oxt cell structure, but not on ASD‐relevant behavior. We interpret these results as inconsistent with our starting hypothesis that reduced Pten function in Oxt‐expressing cells causes the behavioral deficits observed in germline Pten+/− mice. Autism Res 2016, 9: 1248–1262. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 25, 2016   doi: 10.1002/aur.1641   open full text
  • Prevalence and associated features of autism spectrum disorder in extremely low gestational age newborns at age 10 years.
    Robert M. Joseph, Thomas M. O'Shea, Elizabeth N. Allred, Tim Heeren, Deborah Hirtz, Nigel Paneth, Alan Leviton, Karl C. K. Kuban.
    Autism Research. May 25, 2016
    We sought to estimate the prevalence of autism spectrum disorder (ASD) in children born extremely preterm relative to the U.S. population risk of 1.5% [CDC, 2014] using the best‐available diagnostic procedures and minimizing confounding with other neurodevelopmental impairments. Eight hundred and eighty nine of 966 (92%) 10‐year‐old children from the Extremely Low Gestational Age Newborn birth cohort, delivered at 23–27 weeks gestation in 2002–2004, participated. Children meeting ASD screening criteria on the Social Communication Questionnaire were evaluated with the Autism Diagnostic Interview–Revised (ADI‐R). Those meeting ADI‐R criteria were assessed with the Autism Diagnostic Observation Schedule‐2 (ADOS‐2). A positive ADOS‐2 score was the criterion for ASD. Twenty‐six participants were not assessed for ASD because of severe sensory or motor impairment. In the remaining sample, 61 children met criteria for ASD, resulting in a prevalence of 7.1% (95% CI = 5.5–9.0). ASD risk decreased with increasing gestational age, from 15.0% (95% CI = 10.0–21.2) for 23–24 weeks, 6.5% (95% CI = 4.2–9.4) for 25–26 weeks, to 3.4% (95% CI = 1.6–6.1) for 27 weeks gestational age, and this association was independent of IQ. Among children with ASD, 40% had intellectual disability. The male‐to‐female ratio of children with ASD was 2.1:1 (95% CI = 1.2:1–3.5:1), lower than in the general population (4:1). ASD prevalence in the ELGAN cohort was four times higher than in the general population, and was strongly associated with gestational age, underscoring the need for enhanced ASD screening of children born preterm, and suggesting that some risk factors associated with preterm birth may also play a role in the etiology of autism. Autism Res 2017, 10: 224–232. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 25, 2016   doi: 10.1002/aur.1644   open full text
  • A sexually dichotomous, autistic‐like phenotype is induced by Group B Streptococcus maternofetal immune activation.
    Marie‐Julie Allard, Julie D. Bergeron, Moogeh Baharnoori, Lalit K. Srivastava, Louis‐Charles Fortier, Claire Poyart, Guillaume Sébire.
    Autism Research. May 25, 2016
    Group B Streptococcus (GBS) is a commensal bacterium present in the lower genital tract of 15–30% of healthy pregnant women. GBS is the leading cause of chorioamnionitis and cerebral injuries in newborns, occurring most often in the absence of maternofetal pathogen translocation. Despite GBS being the most frequent bacterium colonizing pregnant women, no preclinical studies have investigated the impact of end‐gestational maternal GBS exposure on the offspring's brain development and its behavioral correlates. Our hypothesis is that GBS‐induced gestational infection/inflammation has a deleterious neurodevelopmental impact on uninfected offspring. Our goal was to study the impact of maternal GBS infection on the placental and neurodevelopmental features in the offspring using a new preclinical rat model. GBS‐exposed placentas exhibited chorioamnionitis characterized by the presence of Gram‐positive cocci and polymorphonuclear cells, with the latter being significantly more prominent in the labyrinth of male offspring. GBS‐exposed male offspring had reduced thickness of periventricular white matter. In addition, they exhibited autistic‐like behaviors, such as abnormal social interaction and communication, impaired processing of sensory information and hyperactivity. Overall, these data show for the first time that gestational exposure to GBS plays an important role in the generation of neurodevelopmental abnormalities reminiscent of human autism spectrum disorders (ASD). These results provide new evidence in favor of the role of a common and modifiable infectious/inflammatory environmental factor in human ASD pathophysiology. Autism Res 2017, 10: 233–245. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 25, 2016   doi: 10.1002/aur.1647   open full text
  • Impaired downregulation of visual cortex during auditory processing is associated with autism symptomatology in children and adolescents with autism spectrum disorder.
    R. Joanne Jao Keehn, Sandra S. Sanchez, Claire R. Stewart, Weiqi Zhao, Emily L. Grenesko‐Stevens, Brandon Keehn, Ralph‐Axel Müller.
    Autism Research. May 20, 2016
    Autism spectrum disorders (ASD) are pervasive developmental disorders characterized by impairments in language development and social interaction, along with restricted and stereotyped behaviors. These behaviors often include atypical responses to sensory stimuli; some children with ASD are easily overwhelmed by sensory stimuli, while others may seem unaware of their environment. Vision and audition are two sensory modalities important for social interactions and language, and are differentially affected in ASD. In the present study, 16 children and adolescents with ASD and 16 typically developing (TD) participants matched for age, gender, nonverbal IQ, and handedness were tested using a mixed event‐related/blocked functional magnetic resonance imaging paradigm to examine basic perceptual processes that may form the foundation for later‐developing cognitive abilities. Auditory (high or low pitch) and visual conditions (dot located high or low in the display) were presented, and participants indicated whether the stimuli were “high” or “low.” Results for the auditory condition showed downregulated activity of the visual cortex in the TD group, but upregulation in the ASD group. This atypical activity in visual cortex was associated with autism symptomatology. These findings suggest atypical crossmodal (auditory‐visual) modulation linked to sociocommunicative deficits in ASD, in agreement with the general hypothesis of low‐level sensorimotor impairments affecting core symptomatology. Autism Res 2017, 10: 130–143. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 20, 2016   doi: 10.1002/aur.1636   open full text
  • Elevated levels of tissue plasminogen activator and E‐selectin in male children with autism spectrum disorder.
    Şeref Şimşek, İhsan Çetin, Abdullah Çim, Savaş Kaya.
    Autism Research. May 19, 2016
    Although the etiopathology of autism spectrum disorder (ASD) is not clear, immune dysfunction has been proposed as a mechanism for the pathophysiology of ASD. The purpose of this study is to examine serum levels of tissue plasminogen activator (t‐PA) and some adhesion molecules in children with ASD that have not been investigated previously in detail. The study group included 35 male children aged from 2 to 9 diagnosed with ASD according to DSM‐V criteria. Soluble platelet endothelial adhesion molecule‐1 (sPECAM‐1), P‐selectin, E‐selectin, and t‐PA in the serum were determined with enzyme‐linked immunosorbent assay. Autism behavior check list (ABC) is used for the assessment of ASD severity. The levels of t‐PA (P = 0.025) and E‐selectin (P = 0.007) was detected significantly higher in children with ASD than control group. Serum levels of sPECAM‐1 showed statistically significant negative correlation with sensory, body and object‐use, language, social, and self‐help and total scores in the patient group (r = −0.349, P = 0.04; r = −0.411, P = 0.01; r = −0.412, P = 0.01; r = −0.417, P = 0.01, and r = −0.531, P < 0.01, respectively). Serum levels of P‐selectin levels showed statistically significant negative correlation with ABC total score in the patient group (r = −0.378, P = 0.03). It may be suggested that t‐PA, E‐selectin, P‐selectin, and sPECAM‐1 a crucial role in inflammatory conditions in children with ASD. Autism Res 2016, 9: 1241–1247. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 19, 2016   doi: 10.1002/aur.1638   open full text
  • Personal space regulation in childhood autism: Effects of social interaction and person's perspective.
    Michela Candini, Virginia Giuberti, Alessandra Manattini, Serenella Grittani, Giuseppe di Pellegrino, Francesca Frassinetti.
    Autism Research. May 09, 2016
    Studies in children with Typical Development (TD) and with Autism Spectrum Disorder (ASD) revealed that autism affects the personal space regulation, influencing both its size (permeability) and its changes depending on social interaction (flexibility). Here, we investigate how the nature of social interaction (Cooperative vs. Uncooperative) and the person perspective influence permeability and flexibility of interpersonal distance. Moreover, we tested whether the deficit observed in ASD children, reflects the social impairment (SI) in daily interactions. The stop‐distance paradigm was used to measure the preferred distance between the participant and an unfamiliar adult (first‐person perspective, Experiment 1), and between two other people (third‐person perspective, Experiment 2). Interpersonal distance was measured before and after the interaction with a confederate. The Wing Subgroups Questionnaire was used to evaluate SI in everyday activities, and each ASD participant was accordingly assigned either to the lower (children with low social impairment [low‐SI ASD]), or to the higher SI group (children with high social impairment [high‐SI ASD]). We observed larger interpersonal distance (permeability) in both ASD groups compared to TD children. Moreover, depending on the nature of social interaction, a modulation of interpersonal distance (flexibility) was observed in TD children, both from the first‐ and third‐person perspective. Similar findings were found in low‐SI but not in high‐SI ASD children, in Experiment 1. Conversely, in Experiment 2, no change was observed in both ASD groups. These findings reveal that SI severity and a person's perspective may account for the deficit observed in autism when flexibility, but not permeability, of personal space is considered. Autism Res 2017, 10: 144–154. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 09, 2016   doi: 10.1002/aur.1637   open full text
  • Atypical rapid audio‐visual temporal recalibration in autism spectrum disorders.
    Jean‐Paul Noel, Matthew A. De Niear, Ryan Stevenson, David Alais, Mark T. Wallace.
    Autism Research. May 09, 2016
    Changes in sensory and multisensory function are increasingly recognized as a common phenotypic characteristic of Autism Spectrum Disorders (ASD). Furthermore, much recent evidence suggests that sensory disturbances likely play an important role in contributing to social communication weaknesses—one of the core diagnostic features of ASD. An established sensory disturbance observed in ASD is reduced audiovisual temporal acuity. In the current study, we substantially extend these explorations of multisensory temporal function within the framework that an inability to rapidly recalibrate to changes in audiovisual temporal relations may play an important and under‐recognized role in ASD. In the paradigm, we present ASD and typically developing (TD) children and adolescents with asynchronous audiovisual stimuli of varying levels of complexity and ask them to perform a simultaneity judgment (SJ). In the critical analysis, we test audiovisual temporal processing on trial t as a condition of trial t − 1. The results demonstrate that individuals with ASD fail to rapidly recalibrate to audiovisual asynchronies in an equivalent manner to their TD counterparts for simple and non‐linguistic stimuli (i.e., flashes and beeps, hand‐held tools), but exhibit comparable rapid recalibration for speech stimuli. These results are discussed in terms of prior work showing a speech‐specific deficit in audiovisual temporal function in ASD, and in light of current theories of autism focusing on sensory noise and stability of perceptual representations. Autism Res 2017, 10: 121–129. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 09, 2016   doi: 10.1002/aur.1633   open full text
  • Sensory subtypes and associated outcomes in children with autism spectrum disorders.
    Karla K. Ausderau, John Sideris, Lauren M. Little, Melissa Furlong, John C. Bulluck, Grace T. Baranek.
    Autism Research. May 02, 2016
    Sensory features are prevalent and heterogeneous across children with ASD and these features have been associated with child outcomes. Identification of clinically defined sensory subtypes may enhance our understanding of unique phenotypes that have implications for etiology, prognosis, and intervention. This longitudinal study used a national online survey aimed to identify associations of previously validated sensory subtypes to specific child and family characteristics and functional outcomes [vineland adaptive behavior scale‐II (VABS) and parenting stress index short form (PSI)]. The sensory experiences questionnaire‐3.0 was collected from caregivers with children with ASD, ages 2–12, at two time points (Time 1, n = 1307, Time 2, n = 884), 1 year apart. Functional outcomes assessments were collected at the second time point. A latent profile transition analysis (LPTA) was used to test associations, and results indicated that the attenuated‐preoccupied subtype presented with the significantly lowest levels of VABS adaptive behavior composite scores compared to the other three sensory subtypes. Both the VABS maladaptive behavior index and the total PSI score were significantly highest in the extreme‐mixed subtype. These results underscore the clinical utility of this subtyping approach for differentiating characteristics and functional outcomes associated with clinically defined sensory phenotypes. These findings may have implications for better understanding etiology, prognosis, and more precise targets for interventions designed to ameliorate sensory difficulties, and ultimately mitigate negative developmental consequences and parenting stress. Autism Res 2016, 9: 1316–1327. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    May 02, 2016   doi: 10.1002/aur.1626   open full text
  • Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress.
    Patrick M. Hecht, Melissa Hudson, Susan L. Connors, Michael R. Tilley, Xudong Liu, David Q. Beversdorf.
    Autism Research. April 19, 2016
    Stress exposure during gestation is implicated in several neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous research showed that prenatal stress increases risk for ASD with peak exposure during the end of the second and the beginning of the third trimester. However, exposures to prenatal stress do not always result in ASD, suggesting that other factors may interact with environmental stressors to increase ASD risk. The present study examined a maternal genetic variation in the promoter region of the serotonin transporter gene (5‐HTTLPR) affecting stress tolerance and its interaction with the effect of environmental stressors on risk for ASD. Two independent cohorts of mothers of ASD children recruited by the University of Missouri and Queen's University were surveyed regarding the prenatal environment and genotyping on 5‐HTTLPR was performed to explore this relationship. In both samples, mothers of children with ASD carrying the stress susceptible short allele variant of 5‐HTTLPR experienced a greater number of stressors and greater stress severity when compared to mothers carrying the long allele variant. The temporal peak of stressors during gestation in these mothers was consistent with previous findings. Additionally, increased exposure to prenatal stress was not reported in the pregnancies of typically developing siblings from the same mothers, regardless of maternal genotype, suggesting against the possibility that the short allele might increase the recall of stress during pregnancy. The present study provides further evidence of a specific maternal polymorphism that may affect the risk for ASD with exposure to prenatal stress. Autism Res 2016, 9: 1151–1160. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    April 19, 2016   doi: 10.1002/aur.1629   open full text
  • Exploring ‘The autisms’ at a cognitive level.
    Cathriona Cantio, Jens Richardt Møllegaard Jepsen, Gitte Falcher Madsen, Niels Bilenberg, Sarah J. White.
    Autism Research. April 19, 2016
    The autism spectrum is characterized by genetic and behavioral heterogeneity. However, it is still unknown whether there is a universal pattern of cognitive impairment in autism spectrum disorder (ASD) and whether multiple cognitive impairments are needed to explain the full range of behavioral symptoms. This study aimed to determine whether three widely acknowledged cognitive abnormalities (Theory of Mind (ToM) impairment, Executive Function (EF) impairment, and the presence of a Local Processing Bias (LB)) are universal and fractionable in autism, and whether the relationship between cognition and behavior is dependent on the method of behavioral assessment. Thirty‐one high‐functioning children with ASD and thirty‐seven children with neurotypical development (NTD), comparable in age, gender and Intelligence Quotient (IQ), completed several tasks tapping into ToM, EF, and LB, and autistic symptomatology was assessed through parental and teacher questionnaires, parental interview and direct observation. We found that ToM and EF deficits differentiated the groups and some ToM and EF tasks were related to each other. ToM and EF were together able to correctly classify more than three‐quarters of the children into cases and controls, despite relating to none of the specific behavioral measures. Only a small subgroup of individuals displayed a LB, which was unrelated to ToM and EF, and did not aid diagnostic classification, most likely contributing to non‐diagnostic symptoms in a subgroup. Despite the characteristic heterogeneity of the autism spectrum, it remains a possibility therefore that a single cognitive cause may underlie the range of diagnostic symptoms in all individuals with autism. Autism Res 2016, 9: 1328–1339. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    April 19, 2016   doi: 10.1002/aur.1630   open full text
  • The role of interstimulus interval and “Stimulus‐type” in prepotent response inhibition abilities in people with ASD: A quantitative and qualitative review.
    Marieke W.M. Kuiper, Elisabeth W.M. Verhoeven, Hilde M. Geurts.
    Autism Research. April 19, 2016
    Autism spectrum disorders (ASD) are associated with prepotent response inhibition difficulties. However, the large variation between studies suggests that understudied factors, such as interstimulus interval (ISI) and “stimulus‐type” (both hypothesized proxies of stressors influencing arousal), might influence the inhibitory abilities of people with ASD. Using meta‐analysis, we tested whether differences in prepotent response inhibition between people with and without ASD was influenced by ISI. There was not enough variation in “stimulus‐type” between the studies to include it as a moderator. Thirty‐seven studies met inclusion criteria, with a combined sample size of 950 people with ASD and 966 typically developing controls. Additionally, a qualitative review including studies comparing a neutral and an arousing condition in one experiment was performed to examine whether fast ISI or specific arousing stimuli directly influence prepotent response inhibition. The meta‐analysis indicated that ISI was not a relevant moderator. The qualitative review showed that ISI and “stimulus‐type” had the same effect for both groups. Although all studies regarding ISI indicated that fast ISI worsened performance, different types of stimuli had either a positive or a negative influence. This could suggest that distinctive stimuli might affect arousal differently. While we replicated the inhibition difficulties in people with ASD (g = .51), our results do not show strong ASD‐specific effects of ISI or “stimulus‐type” on inhibition. Nonetheless, ISI and “stimulus‐type” do seem to influence performance. Future research focusing on potential underlying factors (e.g., baseline physiological arousal) is needed to examine why this is the case. Autism Res 2016, 9: 1124–1141. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    April 19, 2016   doi: 10.1002/aur.1631   open full text
  • Discourse comprehension in autism spectrum disorder: Effects of working memory load and common ground.
    Jillian M. Schuh, Inge‐Marie Eigsti, Daniel Mirman.
    Autism Research. April 19, 2016
    Pragmatic language impairments are nearly universal in autism spectrum disorders (ASD). Discourse requires that we monitor information that is shared or mutually known, called “common ground.” While many studies have examined the role of Theory of Mind (ToM) in such impairments, few have examined working memory (WM). Common ground impairments in ASD could reflect limitations in both WM and ToM. This study explored common ground use in youth ages 8–17 years with high‐functioning ASD (n = 13) and typical development (n = 22); groups did not differ on age, gender, IQ, or standardized language. We tracked participants' eye movements while they performed a discourse task in which some information was known only to the participant (e.g., was privileged; a manipulation of ToM). In addition, the amount of privileged information varied (a manipulation of WM). All participants were slower to fixate the target when considering privileged information, and this effect was greatest during high WM load trials. Further, the ASD group was more likely to fixate competing (non‐target) shapes. Predictors of fixation patterns included ASD symptomatology, language ability, ToM, and WM. Groups did not differ in ToM. Individuals with better WM fixated the target more rapidly, suggesting an association between WM capacity and efficient discourse. In addition to ToM knowledge, WM capacity constrains common ground representation and impacts pragmatic skills in ASD. Social impairments in ASD are thus associated with WM capacity, such that deficits in domain‐general, nonsocial processes such as WM exert an influence during complex social interactions. Autism Res 2016, 9: 1340–1352. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    April 19, 2016   doi: 10.1002/aur.1632   open full text
  • Associations between joint attention and language in autism spectrum disorder and typical development: A systematic review and meta‐regression analysis.
    Kristen Bottema‐Beutel.
    Autism Research. April 05, 2016
    Using a structured literature search and meta‐regression procedures, this study sought to determine whether associations between joint attention and language are moderated by group (autism spectrum disorder [ASD] vs. typical development [TD]), joint attention type (responding to joint attention [RJA] vs. other), and other study design features and participant characteristics. Studies were located using database searches, hand searches, and electronic requests for data from experts in the field. This resulted in 71 reports or datasets and 605 effect sizes, representing 1,859 participants with ASD and 1,835 TD participants. Meta‐regression was used to answer research questions regarding potential moderators of the effect sizes of interest, which were Pearson's r values quantifying the association between joint attention and language variables. In the final models, conducted separately for each language variable, effect sizes were significantly higher for the ASD group as compared to the TD group, and for RJA as compared to non‐RJA joint attention types. Approximate mental age trended toward significance for the expressive language model. Joint attention may be more tightly tied to language in children with ASD as compared to TD children because TD children exhibit joint attention at sufficient thresholds so that language development becomes untethered to variations in joint attention. Conversely, children with ASD who exhibit deficits in joint attention develop language contingent upon their joint attention abilities. Because RJA was more strongly related to language than other types of joint attention, future research should involve careful consideration of the operationalization and measurement of joint attention constructs. Autism Res 2016, 9: 1021–1035. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    April 05, 2016   doi: 10.1002/aur.1624   open full text
  • Identifying children with autism spectrum disorder based on their face processing abnormality: A machine learning framework.
    Wenbo Liu, Ming Li, Li Yi.
    Autism Research. April 01, 2016
    The atypical face scanning patterns in individuals with Autism Spectrum Disorder (ASD) has been repeatedly discovered by previous research. The present study examined whether their face scanning patterns could be potentially useful to identify children with ASD by adopting the machine learning algorithm for the classification purpose. Particularly, we applied the machine learning method to analyze an eye movement dataset from a face recognition task [Yi et al., 2016], to classify children with and without ASD. We evaluated the performance of our model in terms of its accuracy, sensitivity, and specificity of classifying ASD. Results indicated promising evidence for applying the machine learning algorithm based on the face scanning patterns to identify children with ASD, with a maximum classification accuracy of 88.51%. Nevertheless, our study is still preliminary with some constraints that may apply in the clinical practice. Future research should shed light on further valuation of our method and contribute to the development of a multitask and multimodel approach to aid the process of early detection and diagnosis of ASD. Autism Res 2016, 9: 888–898. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    April 01, 2016   doi: 10.1002/aur.1615   open full text
  • Screening for co‐occurring conditions in adults with autism spectrum disorder using the strengths and difficulties questionnaire: A pilot study.
    James Findon, Tim Cadman, Catherine S. Stewart, Emma Woodhouse, Hanna Eklund, Hannah Hayward, Daniel De Le Harpe Golden, Eddie Chaplin, Karen Glaser, Emily Simonoff, Declan Murphy, Patrick F. Bolton, Fiona S. McEwen.
    Autism Research. March 28, 2016
    Adolescents and adults with autism spectrum disorder (ASD) are at elevated risk of co‐occurring mental health problems. These are often undiagnosed, can cause significant impairment, and place a very high burden on family and carers. Detecting co‐occurring disorders is extremely important. However, there is no validated screening tool for this purpose. The aim of this pilot study is to test the utility of the strengths and difficulties questionnaire (SDQ) to screen for co‐occurring emotional disorders and hyperactivity in adolescents and adults with ASD. The SDQ was completed by 126 parents and 98 individuals with ASD (in 79 cases both parent and self‐report were available from the same families). Inter‐rater reliability, test‐retest stability, internal consistency, and construct validity were examined. SDQ subscales were also compared to clinically utilized measures of emotional disorders and hyperactivity to establish the ability to predict risk of disorder. Inter‐rater reliability (r = 0.42), test‐retest stability (r = 0.64), internal consistency (α = 0.52–0.81) and construct validity (r = 0.42–0.57) for the SDQ subscales were comparable to general population samples. Parent‐ and self‐report SDQ subscales were significantly associated with measures of anxiety, depression and hyperactivity (62–74% correctly classified). Parent‐report performed significantly better than self‐report; adults with ASD under‐reported difficulties. The SDQ shows promise as a simple and efficient way to screen for emotional disorders and hyperactivity in adolescents and adults with ASD that could help reduce the impact of these disorders on individuals and their families. However, further more systematic attempts at validation are warranted. Autism Res 2016, 9: 1353–1363. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    March 28, 2016   doi: 10.1002/aur.1625   open full text
  • Cerebellar gray matter differentiates children with early language delay in autism.
    Anila M. D'Mello, Dorothea M. Moore, Deana Crocetti, Stewart H. Mostofsky, Catherine J. Stoodley.
    Autism Research. March 22, 2016
    Early language delay (ELD) is one of the earliest indicators of autism spectrum disorder (ASD), and predicts later cognitive and behavioral outcomes. We aimed to determine the neural correlates of ELD in autism, and examine the relationships between gray matter (GM), age of first word/phrase, and core ASD symptoms. We used voxel‐based morphometry to examine whole‐brain differences in GM in 8–13 year old children with autism (n = 13 ELD; n = 22 non‐ELD) and 35 age‐matched typically developing (TD) children. Multiple regression analyses examined the relationships between GM, age of first word/phrase, and autism diagnostic observation schedule (ADOS) scores. Composite age of first word/phrase negatively correlated with GM throughout the cerebellum. Both ASD groups (ELD and non‐ELD) had reduced GM in right cerebellar Crus I/II when compared to TD children. Left cerebellar Crus I/II was the only region in the brain that differentiated ELD and non‐ELD children, with ELD children showing reduced GM relative to both non‐ELD and TD groups. Group×score interactions converged in left Crus I/II, such that the non‐ELD group showed poorer ADOS scores with increasing GM, whereas the ELD group showed poorer ADOS scores as GM decreased. Reduced GM in right cerebellar Crus I/I was related ASD diagnosis, while children with ELD showed additional reduced GM in left Crus I/II. These findings highlight the importance of specific cerebellar networks in both ASD and early language development, and suggest that bilateral disruption in cerebellar regions that interconnect with fronto‐parietal networks could impact language acquisition in ASD. Autism Res 2016, 9: 1191–1204. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    March 22, 2016   doi: 10.1002/aur.1622   open full text
  • Atypical effective connectivity of thalamo‐cortical circuits in autism spectrum disorder.
    Heng Chen, Lucina Q. Uddin, Youxue Zhang, Xujun Duan, Huafu Chen.
    Autism Research. March 22, 2016
    Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by atypical connectivity within and across multiple brain systems. We aimed to explore information transmission from the sensory periphery to information processing centers of the brain across thalamo‐cortical circuits in ASD. A large multicenter dataset from the autism brain imaging data exchange was utilized. A thalamus template derived from the Automatic Anatomic Labeling atlas was subdivided into six subregions corresponding to six cortical regions using a “winner‐takes‐all” strategy. Granger causality analysis (GCA) was then applied to calculate effective connectivity from subregions of the thalamus to the corresponding cortical regions. Results demonstrate reduced effective connectivity from the thalamus to left prefrontal cortex (P = 0.023), right posterior parietal cortex (P = 0.03), and bilateral temporal cortex (left: P = 0.014; right: P = 0.015) in ASD compared with healthy control (HC) participants. The GCA values of the thalamus‐bilateral temporal cortex connections were significantly negatively correlated with communication scores as assessed by the autism diagnostic observation schedule in the ASD group (left: P = 0.037; right: P = 0.007). Age‐related analyses showed that the strengths of the thalamus‐bilateral temporal cortex connections were significantly positively correlated with age in the HC group (left: P = 0.013; right: P = 0.016), but not in the ASD group (left: P = 0.506; right: P = 0.219). These results demonstrate impaired thalamo‐cortical information transmission in ASD and suggest that atypical development of thalamus‐temporal cortex connections may relate to communication deficits in the disorder. Autism Res 2016, 9: 1183–1190. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    March 22, 2016   doi: 10.1002/aur.1614   open full text
  • Reduced goal‐directed action control in autism spectrum disorder.
    Gail A. Alvares, Bernard W. Balleine, Lisa Whittle, Adam J. Guastella.
    Autism Research. March 21, 2016
    Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental conditions associated with persistent, stereotyped or repetitive actions, and patterns of interest that are maintained in spite of possible negative outcomes. The aim of the present study was to investigate whether impairments in the ability to execute flexible goal‐directed actions may be an underlying feature in ASD contributing to these symptoms. Young adults diagnosed with ASD were recruited along with controls and adults with social anxiety disorder (SAD). Participants were trained to make keyboard actions for food outcomes and then subsequently allowed to consume one outcome till satiety. As expected, this outcome devaluation procedure reduced subsequent responding for actions predicting the devalued outcome, while maintaining responding on the other still‐valued action, in controls. However, both ASD and SAD participants were unable to demonstrate flexible goal‐directed actions, and were insensitive to the change in outcome value on subsequent action control. This behavioral deficit was not due to impairments in appropriate contingency awareness, as all groups rated the devalued food outcome as less pleasant after devaluation. A lack of control over actions may underlie persistent and habitual actions in anxiety‐inducing contexts typical in both ASD and SAD, such as avoidance and safety behaviors. Using a translational behavioral paradigm, this study demonstrated that individuals with ASD are unable to use changes in the environment to flexibly update their behavior in the same context. This reduced behavioral control may underlie persistence of intrusive actions and restricted inflexible cognition, representing a specific area for targeted behavioral interventions. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2016, 9: 1285–1293. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    March 21, 2016   doi: 10.1002/aur.1613   open full text
  • Dopaminergic variants in siblings at high risk for autism: Associations with initiating joint attention.
    Devon N. Gangi, Daniel S. Messinger, Eden R. Martin, Michael L. Cuccaro.
    Autism Research. March 15, 2016
    Younger siblings of children with autism spectrum disorder (ASD; high‐risk siblings) exhibit lower levels of initiating joint attention (IJA; sharing an object or experience with a social partner through gaze and/or gesture) than low‐risk siblings of children without ASD. However, high‐risk siblings also exhibit substantial variability in this domain. The neurotransmitter dopamine is linked to brain areas associated with reward, motivation, and attention, and common dopaminergic variants have been associated with attention difficulties. We examined whether these common dopaminergic variants, DRD4 and DRD2, explain variability in IJA in high‐risk (n = 55) and low‐risk (n = 38) siblings. IJA was assessed in the first year during a semi‐structured interaction with an examiner. DRD4 and DRD2 genotypes were coded according to associated dopaminergic functioning to create a gene score, with higher scores indicating more genotypes associated with less efficient dopaminergic functioning. Higher dopamine gene scores (indicative of less efficient dopaminergic functioning) were associated with lower levels of IJA in the first year for high‐risk siblings, while the opposite pattern emerged in low‐risk siblings. Findings suggest differential susceptibility—IJA was differentially associated with dopaminergic functioning depending on familial ASD risk. Understanding genes linked to ASD‐relevant behaviors in high‐risk siblings will aid in early identification of children at greatest risk for difficulties in these behavioral domains, facilitating targeted prevention and intervention. Autism Res 2016, 9: 1142–1150. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    March 15, 2016   doi: 10.1002/aur.1623   open full text
  • Aging and autism spectrum disorder: Evidence from the broad autism phenotype.
    Gregory L. Wallace, Jessica Budgett, Rebecca A. Charlton.
    Autism Research. March 11, 2016
    This study investigated for the first time the broad autism phenotype (BAP) in the context of older adulthood and its associations with real‐world executive function, social support, and both depression and anxiety symptomatology. Based on self‐ratings of autistic traits, 66 older adults (60+ years old, range = 61–88) were split into BAP (n = 20) and control (n = 46) groups. Individuals in the BAP group, even after controlling for age, education level, sex, and health problems, exhibited more real‐world executive function problems in multiple domains, reported lower levels of social support, and self‐rated increased depression and anxiety symptomatology compared to the control group. Regression analysis revealed that level of social support was the strongest predictor of BAP traits across both groups, although real‐world executive function problems and depression symptomatology were also significant predictors. Moreover, when predicting anxiety and depression symptomatology, BAP traits were the strongest predictors above and beyond the effects of demographic factors, real‐world executive function problems, and social support levels. These findings suggest that the BAP in older adulthood imparts additional risks to areas of functioning that are known to be crucial to aging‐related outcomes in the context of typical development. These results might in turn inform aging in autism spectrum disorder, which has been largely unexplored to date. Autism Res 2016, 9: 1294–1303. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    March 11, 2016   doi: 10.1002/aur.1620   open full text
  • Relations between language and cognition in native‐signing children with autism spectrum disorder.
    Aaron Shield, Jennie Pyers, Amber Martin, Helen Tager‐Flusberg.
    Autism Research. March 03, 2016
    Two populations have been found to exhibit delays in theory of mind (ToM): deaf children of hearing parents and children with autism spectrum disorder (ASD). Deaf children exposed to sign from birth by their deaf parents, however, show no such delay, suggesting that early language exposure is key to ToM development. Sign languages also present frequent opportunities with visual perspective‐taking (VPT), leading to the question of whether sign exposure could benefit children with ASD. We present the first study of children with ASD exposed to sign from birth by their deaf parents. Seventeen native‐signing children with a confirmed ASD diagnosis and a chronological‐ and mental age‐matched control group of 18 typically developing (TD) native‐signing deaf children were tested on American Sign Language (ASL) comprehension, two minimally verbal social cognition tasks (ToM and VPT), and one spatial cognition task (mental rotation). The TD children outperformed the children with ASD on ASL comprehension (p < 0.0001), ToM (p = 0.02), and VPT (p < 0.01), but not mental rotation (p = 0.12). Language strongly correlated with ToM (p < 0.01) and VPT (p < 0.001), but not mental rotation (p = ns). Native exposure to sign is thus insufficient to overcome the language and social impairments implicated in ASD. Contrary to the hypothesis that sign could provide a scaffold for ToM skills, we find that signing children with ASD are unable to access language so as to gain any potential benefit sign might confer. Our results support a strong link between the development of social cognition and language, regardless of modality, for TD and ASD children. Autism Res 2016, 9: 1304–1315. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    March 03, 2016   doi: 10.1002/aur.1621   open full text
  • Differences in age‐dependent neural correlates of semantic processing between youths with autism spectrum disorder and typically developing youths.
    Pin‐Jane Chen, Susan Shur‐Fen Gau, Shu‐Hui Lee, Tai‐Li Chou.
    Autism Research. February 21, 2016
    Individuals with autism spectrum disorders (ASD) have aberrant neural activity during semantic judgments. We aimed to examine age‐dependent neural correlates of semantic processing in boys with ASD as compared to typically developing boys (TD). We used functional MRI to investigate 37 boys with ASD (mean age = 13.3 years, standard deviation = 2.4) and 35 age‐, sex‐, Intelligence quotient (IQ)‐ and handedness‐matched TD boys (mean age = 13.3 years, standard deviation = 2.7) from age 8 to 18 years. Participants had to indicate whether pairs of Chinese characters presented visually were related in meaning. Group (ASD, TD) × Age (Old, Young) ANOVA was used to examine the difference of age‐related changes. Direct comparisons between the adolescent group and the child group were also performed. The behavioral results showed that the ASD group had lower accuracy in the related condition relative to the TD group. The neuroimaging results showed greater activation in the cuneus and less activation in the left inferior frontal gyrus in boys with ASD than TD boys. Children with ASD produced greater activation in the cuneus than TD children. Adolescents with ASD showed reduced left IFG activation as compared to TD adolescents. Our findings suggest that TD boys may engage more in higher‐level processing of retrieving or selecting semantic features while boys with ASD may rely more on lower‐level visual processing during semantic judgments. The findings imply different functional organizations of the semantic system between the two groups. Autism Res 2016, 9: 1263–1273. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    February 21, 2016   doi: 10.1002/aur.1616   open full text
  • Executive function predicts the development of play skills for verbal preschoolers with autism spectrum disorders.
    Susan Faja, Geraldine Dawson, Katherine Sullivan, Andrew N. Meltzoff, Annette Estes, Raphael Bernier.
    Autism Research. February 18, 2016
    Executive function and play skills develop in early childhood and are linked to cognitive and language ability. The present study examined these abilities longitudinally in two groups with autism spectrum disorder—a group with higher initial language (n = 30) and a group with lower initial language ability (n = 36). Among the lower language group, concurrent nonverbal cognitive ability contributed most to individual differences in executive function and play skills. For the higher language group, executive function during preschool significantly predicted play ability at age 6 over and above intelligence, but early play did not predict later executive function. These results suggested that factors related to the development of play and executive function differ for subgroups of children with different language abilities and that early executive function skills may be critical in order for verbal children with autism to develop play. Autism Res 2016, 9: 1274–1284. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    February 18, 2016   doi: 10.1002/aur.1608   open full text
  • Development of the anxiety scale for children with autism spectrum disorder (ASC‐ASD).
    Jacqui Rodgers, Sarah Wigham, Helen McConachie, Mark Freeston, Emma Honey, Jeremy R. Parr.
    Autism Research. February 17, 2016
    Many children with autism spectrum disorder (ASD) experience high levels of anxiety. A widely used measure for typically developing children is the Revised Child Anxiety and Depression Scale (RCADS). However, such anxiety measures may require adaptation to accommodate characteristics of those with ASD. An adapted version of the RCADS was created based on empirical evidence of anxiety phenomenology in ASD, which included additional items related to sensory anxiety, intolerance of uncertainty, and phobias. Content validity was refined during focus groups with parents. Polychoric factor analysis was undertaken on data from 170 children with ASD, aged 8‐16, and their parents. This process resulted in the creation of a new 24 item scale (self and parent report) each with four subscales: Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety, with evidence of good reliability and validity. The freely available Anxiety Scale for Children ‐ ASD, Parent and Child versions (ASC‐ASD) has promising psychometric properties including good internal consistency, validity, and 1 month test–retest reliability. Autism Res 2016, 9: 1205–1215. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    February 17, 2016   doi: 10.1002/aur.1603   open full text
  • Deficient visuospatial working memory functions and neural correlates of the default‐mode network in adolescents with autism spectrum disorder.
    Hsiang‐Yun Chien, Susan Shur‐Fen Gau, Wen‐Yih Isaac Tseng.
    Autism Research. February 01, 2016
    In addition to the essential features of autism spectrum disorder (ASD), namely social communication deficits and repetitive behaviors, individuals with ASD may suffer from working memory deficits and an altered default‐mode network (DMN). We hypothesized that an altered DMN is related to working memory deficits in those with ASD. A total of 37 adolescents with ASD and 36 age‐ and IQ‐matched typically developing (TD) controls were analyzed. Visuospatial working memory performance was assessed using pattern recognition memory (PRM), spatial recognition memory (SRM), and paired‐associates learning (PAL) tasks. The intrinsic functional connectivity (iFC) of the DMN was indexed by the temporal correlations between the resting‐state functional magnetic resonance imaging signals of pairs of DMN regions, including those between the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) and between the PCC and parahippocampi (PHG). The corresponding structural connectivity of the DMN was indexed by the generalized fractional anisotropy (GFA) of the dorsal and ventral cingulum bundles on the basis of diffusion spectrum imaging data. The results showed that ASD adolescents exhibited delayed correct responses in PRM and SRM tasks and committed more errors in the PAL task than the TD controls did. The delayed responses during the PRM and SRM tasks were negatively correlated with bilateral PCC–mPFC iFCs, and PAL performance was negatively correlated with right PCC–PHG iFC in ASD adolescents. Furthermore, ASD adolescents showed significant lower GFA in the right cingulum bundles than the TD group did; the GFA value was negatively correlated with SRM performance in ASD. Our results provide empirical evidence for deficient visuospatial working memory and corresponding neural correlates within the DMN in adolescents with ASD. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    February 01, 2016   doi: 10.1002/aur.1607   open full text
  • Communication growth in minimally verbal children with ASD: The importance of interaction.
    Charlotte DiStefano, Wendy Shih, Ann Kaiser, Rebecca Landa, Connie Kasari.
    Autism Research. January 29, 2016
    Little is known about language development in children with Autism Spectrum Disorders (ASD) who remain minimally verbal past age 5. While there is evidence that children can develop language after age 5, we lack detailed information. Studies of this population generally focus on discrete language skills without addressing broader social‐communication abilities. As communication and social deficits are both inherent to ASD, an examination of not only what language skills are acquired, but how those skills are used in interactions is relevant. Research in typical development has examined how communication interchanges (unbroken back‐and‐forth exchanges around a unified purpose) develop, which can be used as a framework for studying minimally verbal children. This study examined the interchange use by 55 children with ASD over the course of a 6‐month play and engagement‐based communication intervention. Half of the children received intervention sessions that also incorporated a speech‐generating device (SGD). Interchanges were coded by: frequency, length, function, and initiator (child or adult). Results indicated that children initiated a large proportion of interchanges and this proportion increased over time. The average length and number of interchanges increased over time, with children in the SGD group showing even greater growth. Finally, children's total number of interchanges at baseline was positively associated with their spoken language gains over the course of intervention. This study supports the crucial relationship between social engagement and expressive language development, and highlights the need to include sustained communication interchanges as a target for intervention with this population. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 29, 2016   doi: 10.1002/aur.1594   open full text
  • Maternal metabolic risk factors for autism spectrum disorder—An analysis of electronic medical records and linked birth data.
    Natalia Connolly, Julia Anixt, Patty Manning, Daniel Ping‐I Lin, Keith A. Marsolo, Katherine Bowers.
    Autism Research. January 29, 2016
    Past studies have suggested that conditions experienced by women during pregnancy (e.g. obesity and gestational diabetes mellitus (GDM)) may be associated with having a child with autism spectrum disorder (ASD). Our objective was to compare mothers who had a child diagnosed with ASD to mothers of children with a non‐ASD developmental disorder (DD) or without any reported DD (controls). To accomplish the objective we collected medical record data from patients who resided in the Cincinnati Children's Hospital Medical Center's (CCHMC) primary catchment area and linked those data to data from birth certificates (to identify risk factors). Two comparison groups were analyzed; one with DD; and the other, controls without a reported ASD or DD. Descriptive statistics and regression analyses evaluated differences. Differences were greater comparing mothers of ASD to controls than comparing ASD to DD. Maternal obesity and GDM were associated with a statistically significant approximately 1.5‐fold increased odds of having a child with an ASD. For mothers with both GDM and obesity, the association was twofold for having a child with ASD compared with controls. Maternal obesity and GDM might be associated with an increased risk of ASD in the offspring; however, no difference in risk of ASD according to BMI and GDM was seen when comparing to DD. Autism Res 2016, 9: 829–837,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 29, 2016   doi: 10.1002/aur.1586   open full text
  • Atypical development of the central auditory system in young children with Autism spectrum disorder.
    Yuko Yoshimura, Mitsuru Kikuchi, Hirotoshi Hiraishi, Chiaki Hasegawa, Tetsuya Takahashi, Gerard B. Remijn, Manabu Oi, Toshio Munesue, Haruhiro Higashida, Yoshio Minabe, Haruyuki Kojima.
    Autism Research. January 25, 2016
    The P1m component of the auditory evoked magnetic field is the earliest cortical response associated with language acquisition. However, the growth curve of the P1m component is unknown in both typically developing (TD) and atypically developing children. The aim of this study is to clarify the developmental pattern of this component when evoked by binaural human voice stimulation using child‐customized magnetoencephalography. A total of 35 young TD children (32–121 months of age) and 35 children with autism spectrum disorder (ASD) (38–111 months of age) participated in this study. This is the first report to demonstrate an inverted U‐shaped growth curve for the P1m dipole intensity in the left hemisphere in TD children. In addition, our results revealed a more diversified age‐related distribution of auditory brain responses in 3‐ to 9‐year‐old children with ASD. These results demonstrate the diversified growth curve of the P1m component in ASD during young childhood, which is a crucial period for first language acquisition. Autism Res 2016, 9: 1216–1226. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 25, 2016   doi: 10.1002/aur.1604   open full text
  • White matter volume in the brainstem and inferior parietal lobule is related to motor performance in children with autism spectrum disorder: A voxel‐based morphometry study.
    Ryuzo Hanaie, Ikuko Mohri, Kuriko Kagitani‐Shimono, Masaya Tachibana, Junko Matsuzaki, Ikuko Hirata, Fumiyo Nagatani, Yoshiyuki Watanabe, Norihiko Fujita, Masako Taniike.
    Autism Research. January 25, 2016
    Many studies have reported poor motor performance in autism spectrum disorder (ASD); however, the underlying brain mechanisms remain unclear. Recent neuroimaging studies have suggested that abnormalities of the white matter (WM) are related to the features of ASD. In this study, we used voxel‐based morphometry (VBM) to investigate which WM regions correlate with motor performance in children with ASD, and whether the WM volume in those brain regions differed between children with ASD and typically developing (TD) children. The subjects included 19 children with ASD and 20 TD controls. Motor performance was assessed using the Movement Assessment Battery for Children 2 (M‐ABC 2). Children with ASD showed poorer motor performance than did the controls. There was a significant positive correlation between the total test score on the M‐ABC 2 and the volume of WM in the brainstem and WM adjacent to the left supramarginal gyrus (SMG). In addition, compared with the TD controls, children with ASD had a decreased volume of WM in the brainstem and adjacent to the left intraparietal sulcus, which is close to the SMG. These findings suggest that structural changes in the WM in the brainstem and left inferior parietal lobule may contribute to poor motor performance in children with ASD. Autism Res 2016, 9: 981–992. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 25, 2016   doi: 10.1002/aur.1605   open full text
  • Intact recognition, but attenuated adaptation, for biological motion in youth with autism spectrum disorder.
    Jeroen J. A. van Boxtel, Mirella Dapretto, Hongjing Lu.
    Autism Research. January 25, 2016
    Given the ecological importance of biological motion and its relevance to social cognition, considerable effort has been devoted over the past decade to studying biological motion perception in autism. However, previous studies have asked observers to detect or recognize briefly presented human actions placed in isolation, without spatial or temporal context. Research on typical populations has shown the influence of temporal context in biological motion perception: prolonged exposure to one action gives rise to an aftereffect that biases perception of a subsequently displayed action. Whether people with autism spectrum disorders (ASD) show such adaptation effects for biological motion stimuli remains unknown. To address this question, this study examined how well youth with ASD recognize ambiguous actions and adapt to recently‐observed actions. Compared to typically‐developing (TD) controls, youth with ASD showed no differences in perceptual boundaries between actions categories, indicating intact ability in recognizing actions. However, children with ASD showed weakened adaptation to biological motion. It is unlikely that the reduced action adaptability in autism was due to delayed developmental trajectory, as older children with ASD showed weaker adaptation to actions than younger children with ASD. Our results further suggest that high‐level (i.e., action) processing weakens with age for children with ASD, but this change may be accompanied by a potentially compensatory mechanism based on more involvement of low‐level (i.e., motion) processing. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 25, 2016   doi: 10.1002/aur.1595   open full text
  • Uh and um in children with autism spectrum disorders or language impairment.
    Kyle Gorman, Lindsay Olson, Alison Presmanes Hill, Rebecca Lunsford, Peter A. Heeman, Jan P. H. van Santen.
    Autism Research. January 22, 2016
    Atypical pragmatic language is often present in individuals with autism spectrum disorders (ASD), along with delays or deficits in structural language. This study investigated the use of the “fillers” uh and um by children ages 4–8 during the autism diagnostic observation schedule. Fillers reflect speakers' difficulties with planning and delivering speech, but they also serve communicative purposes, such as negotiating control of the floor or conveying uncertainty. We hypothesized that children with ASD would use different patterns of fillers compared to peers with typical development or with specific language impairment (SLI), reflecting differences in social ability and communicative intent. Regression analyses revealed that children in the ASD group were much less likely to use um than children in the other two groups. Filler use is an easy‐to‐quantify feature of behavior that, in concert with other observations, may help to distinguish ASD from SLI. Autism Res 2016, 9: 854–865. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 22, 2016   doi: 10.1002/aur.1578   open full text
  • Meta‐analysis and association of two common polymorphisms of the human oxytocin receptor gene in autism spectrum disorder.
    Thorsten M. Kranz, Marnie Kopp, Regina Waltes, Michael Sachse, Eftichia Duketis, Tomasz A. Jarczok, Franziska Degenhardt, Katharina Görgen, Jobst Meyer, Christine M. Freitag, Andreas G. Chiocchetti.
    Autism Research. January 20, 2016
    Neuropeptides such as oxytocin (OXT) are known facilitators of social behavior across species. Variants of the OXT receptor gene (OXTR) have been tested for association with autism spectrum disorder (ASD) across manifold ethnicities, yielding both positive and negative findings. A recent meta‐analysis, comprising 16 single nucleotide polymorphisms (SNPs), has corroborated the implication of OXTR in the etiology of ASD. Here, we genotyped and tested two additional variants (rs237889 and rs237897) for association with ASD in two German predominantly high‐functioning ASD samples. We found nominal over‐transmission (OR = 1.48, CI95 = 1.06‐2.08, P = 0.022) for the minor A allele of variant rs237889G>A in sample 1 (N = 135 complete parent‐offspring trios, 29 parent child duos), but not in sample 2 (362 trios, 69 duos). Still, in a meta‐analysis comprising four different studies including the two unreported German data sets (N = 542 families), this finding was confirmed (OR = 1.12; CI95 = 1.01–1.24, random effects P = 0.012). In addition, carriers of the minor risk allele rs237889‐A showed significantly increased severity scores, as assessed through the autism diagnostic interview – revised (ADI‐R), with highly significant increases in social interaction deficits. Our results corroborate the implication of common OXTR variants in the etiology of ASD. There is a need for functional studies to delineate the neurobiological implications of this and other association findings. (172/250). Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 20, 2016   doi: 10.1002/aur.1597   open full text
  • A selective impairment in extracting fearful information from another's eyes in Autism.
    Yongning Song, Yuji Hakoda, Biao Sang.
    Autism Research. January 18, 2016
    An atypical pattern of facial expression processing in children with autism spectrum disorder (ASD) has been discussed in previous studies. In this study, we systematically examined the hypothesis of selective abnormality of gaze pattern of in children with ASD using three emotion judgment “bubble” tasks. In this study, we used a data‐driven driven technique, referred to as “Bubbles” to examine the hypothesis that ASD children will not show a general but rather a selective abnormality in extracting eyes information expressed by different emotions. Results indicated that similar to non‐ASD individuals, ASD individuals used information from other people's eyes to judge happiness and anger. In contrast, ASD individuals showed a remarkable reduction in processing the eye region in fearful face, together with enhanced processing of the mouth, compared with the control group. The results suggest that a selective abnormality in extracting eyes information of fearful face without abnormality in processing eyes area of other basic facial emotions is a key and characteristic feature of autistic facial cognition. To our knowledge, this finding regarding the selective abnormality in extracting fearful information from another's eyes in ASDs has never been reported in previous studies and the information gathered as a part of this pilot research project has important clinical implications for social information processing training. For example, as children with ASD are more vulnerable to fear processing, training related to fear should be stressed. Autism Res 2016, 9: 1002–1011. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 18, 2016   doi: 10.1002/aur.1583   open full text
  • Atypical sensory reactivity influences auditory attentional control in adults with autism spectrum disorders.
    Debra S. Karhson, Edward J. Golob.
    Autism Research. January 18, 2016
    Frequent observations of atypical sensory reactivity in people with autism spectrum disorders (ASD) suggest that the perceptual experience of those on the Spectrum is dissimilar to neurotypicals. Moreover, variable attention abilities in people with ASD, ranging from good control to periods of high distractibility, may be related to atypical sensory reactivity. This study used auditory event‐related potential (ERP) measures to evaluate top‐down and bottom‐up attentional processes as a function of perceptual load, and examined these factors with respect to sensory reactivity. Twenty‐five age and IQ‐matched participants (ASD: 22.5 year, SD = 4.1 year; Controls: 22.8 year, SD = 5.1 year) completed the Adolescent/Adult Sensory Profile prior to performing a modified 3‐stimulus (target, non‐target, and distractor) auditory oddball target detection task EEG was recorded during task completion. ERP analysis assessed early sensory processing (P50, ∼50 ms latency; N100, ∼100 ms latency), cognitive control (N200, ∼200 ms latency), and attentional processing (P3a and P3b, ∼300 ms latency). Behavioral data demonstrates participants with ASD and neurotypical performed similarly on auditory target detection, but diverged on sensory profiles. Target ERP measures associated with top‐down control (P3b latency) significantly increased under greater load in controls, but not in participants with ASD. Early ERP responses associated with bottom‐up attention (P50 amplitude) were positively correlated to increased sensory sensitivity. Findings suggest specific neural mechanisms for increased perceptual capacity and enhanced bottom‐up processing of sensory stimuli in people with autism. Results from participants with ASD are consistent with load theory and enhanced perceptual functioning. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 18, 2016   doi: 10.1002/aur.1593   open full text
  • Hemispheric differences in language processing in autism spectrum disorders: A meta‐analysis of neuroimaging studies.
    Abbey J. Herringshaw, Carla J. Ammons, Thomas P. DeRamus, Rajesh K. Kana.
    Autism Research. January 11, 2016
    Language impairments, a hallmark feature of autism spectrum disorders (ASD), have been related to neuroanatomical and functional abnormalities. Abnormal lateralization of the functional language network, increased reliance on visual processing areas, and increased posterior brain activation have all been reported in ASD and proposed as explanatory models of language difficulties. Nevertheless, inconsistent findings across studies have prevented a comprehensive characterization of the functional language network in ASD. The aim of this study was to quantify common and consistent patterns of brain activation during language processing in ASD and typically developing control (TD) participants using a meta‐analytic approach. Activation likelihood estimation (ALE) meta‐analysis was used to examine 22 previously published functional Magnetic Resonance Imaging (fMRI)/positron emission tomography studies of language processing (ASD: N = 328; TD: N = 324). Tasks included in this study addressed semantic processing, sentence comprehension, processing figurative language, and speech production. Within‐group analysis showed largely overlapping patterns of language‐related activation in ASD and TD groups. However, the ASD participants, relative to TD participants, showed: (1) more right hemisphere activity in core language areas (i.e., superior temporal gyrus and inferior frontal gyrus), particularly in tasks where they had poorer performance accuracy; (2) bilateral MTG hypo‐activation across many different paradigms; and (3) increased activation of the left lingual gyrus in tasks where they had intact performance. These findings show that the hypotheses reviewed here address the neural and cognitive aspects of language difficulties in ASD across all tasks only in a limited way. Instead, our findings suggest the nuances of language and brain in ASD in terms of its context‐dependency. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    January 11, 2016   doi: 10.1002/aur.1599   open full text
  • Functioning and disability in autism spectrum disorder: A worldwide survey of experts.
    Elles de Schipper, Soheil Mahdi, Petrus de Vries, Mats Granlund, Martin Holtmann, Sunil Karande, Omar Almodayfer, Cory Shulman, Bruce Tonge, Virginia V.C.N. Wong, Lonnie Zwaigenbaum, Sven Bölte.
    Autism Research. January 08, 2016
    Objective: This study is the second of four to prepare International Classification of Functioning, Disability and Health (ICF; and Children and Youth version, ICF(‐CY)) Core Sets for Autism Spectrum Disorder (ASD).The objective of this study was to survey the opinions and experiences of international experts on functioning and disability in ASD. Methods: Using a protocol stipulated by the World Health Organization (WHO) and monitored by the ICF Research Branch, an email‐based questionnaire was circulated worldwide among ASD experts, and meaningful functional ability and disability concepts were extracted from their responses. These concepts were then linked to the ICF(‐CY) by two independent researchers using a standardized linking procedure. Results: N = 225 experts from 10 different disciplines and all six WHO‐regions completed the survey. Meaningful concepts from the responses were linked to 210 ICF(‐CY) categories. Of these, 103 categories were considered most relevant to ASD (i.e., identified by at least 5% of the experts), of which 37 were related to Activities and Participation, 35 to Body functions, 22 to Environmental factors, and 9 to Body structures. A variety of personal characteristics and ASD‐related functioning skills were provided by experts, including honesty, loyalty, attention to detail and creative talents. Reported gender differences in ASD comprised more externalizing behaviors among males and more internalizing behaviors in females. Conclusion: The ICF(‐CY) categories derived from international expert opinions indicate that the impact of ASD on functioning extends far beyond core symptom domains. Autism Res 2016, 9: 959–969. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    January 08, 2016   doi: 10.1002/aur.1592   open full text
  • Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid‐induced autism.
    Yuta Hara, Yukio Ago, Atsuki Taruta, Keisuke Katashiba, Shigeru Hasebe, Erika Takano, Yusuke Onaka, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma.
    Autism Research. December 30, 2015
    Rodents exposed prenatally to valproic acid (VPA) show autism‐related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA‐treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA‐treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA‐treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA‐induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine‐D1 receptor antagonist SCH39166 or the dopamine‐D2 receptor antagonist raclopride, but not by the α2‐adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA‐treated mice via a prefrontal dopaminergic system‐dependent mechanism. Autism Res 2016, 9: 926–939. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    December 30, 2015   doi: 10.1002/aur.1596   open full text
  • Early gross motor skills predict the subsequent development of language in children with autism spectrum disorder.
    Rachael Bedford, Andrew Pickles, Catherine Lord.
    Autism Research. December 22, 2015
    Background: Motor milestones such as the onset of walking are important developmental markers, not only for later motor skills but also for more widespread social‐cognitive development. The aim of the current study was to test whether gross motor abilities, specifically the onset of walking, predicted the subsequent rate of language development in a large cohort of children with autism spectrum disorder (ASD). Methods: We ran growth curve models for expressive and receptive language measured at 2, 3, 5 and 9 years in 209 autistic children. Measures of gross motor, visual reception and autism symptoms were collected at the 2 year visit. In Model 1, walking onset was included as a predictor of the slope of language development. Model 2 included a measure of non‐verbal IQ and autism symptom severity as covariates. The final model, Model 3, additionally covaried for gross motor ability. Results: In the first model, parent‐reported age of walking onset significantly predicted the subsequent rate of language development although the relationship became non‐significant when gross motor skill, non‐verbal ability and autism severity scores were included (Models 2 & 3). Gross motor score, however, did remain a significant predictor of both expressive and receptive language development. Conclusions: Taken together, the model results provide some evidence that early motor abilities in young children with ASD can have longitudinal cross‐domain influences, potentially contributing, in part, to the linguistic difficulties that characterise ASD. Autism Res 2016, 9: 993–1001. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    December 22, 2015   doi: 10.1002/aur.1587   open full text
  • Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study.
    Zeyan Liew, Beate Ritz, Jasveer Virk, Jørn Olsen.
    Autism Research. December 21, 2015
    Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking. We followed 64,322 children and mothers enrolled in the Danish National Birth Cohort (DNBC; 1996–2002) for average 12.7 years to investigate whether acetaminophen use in pregnancy is associated with increased risk of ASD in the offspring. Information on acetaminophen use was collected prospectively from three computer‐assisted telephone interviews. We used records from the Danish hospital and psychiatric registries to identify diagnoses of ASD. At the end of follow up, 1,027 (1.6%) children were diagnosed with ASD, 345 (0.5%) with infantile autism. We found that 31% of ASD (26% of infantile autism) have also been diagnosed with hyperkinetic disorders. More than 50% women reported ever using acetaminophen in pregnancy. We used Cox proportional hazards model to estimate hazard ratio (HR) and 95% confident interval (CI). Prenatal use of acetaminophen was associated with an increased risk of ASD accompanied by hyperkinetic symptoms (HR = 1.51 95% CI 1.19–1.92), but not with other ASD cases (HR = 1.06 95% CI 0.92–1.24). Longer duration of use (i.e., use for >20 weeks in gestation) increased the risk of ASD or infantile autism with hyperkinetic symptoms almost twofold. Maternal use of acetaminophen in pregnancy was associated with ASD with hyperkinetic symptoms only, suggesting acetaminophen exposure early in fetal life may specifically impact this hyperactive behavioral phenotype. Autism Res 2016, 9: 951–958. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    December 21, 2015   doi: 10.1002/aur.1591   open full text
  • The integrity of lexical acquisition mechanisms in autism spectrum disorders: A research review.
    Sudha Arunachalam, Rhiannon J. Luyster.
    Autism Research. December 21, 2015
    Research on autism spectrum disorders (ASD) has rapidly expanded in recent years, yielding important developments in both theory and practice. While we have gained important insights into how children with ASD differ from typically developing (TD) children in terms of phenotypic features, less has been learned about if and how development in ASD differs from typical development in terms of underlying mechanisms of change. This article aims to provide a review of processes subserving lexical development in ASD, with the goal of identifying contributing factors to the heterogeneity of language outcomes in ASD. The focus is on available evidence of the integrity or disruption of these mechanisms in ASD, as well as their significance for vocabulary development; topics include early speech perception and preference, speech segmentation, word learning, and category formation. Significant gaps in the literature are identified and future directions are suggested. Autism Res 2016, 9: 810–828. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    December 21, 2015   doi: 10.1002/aur.1590   open full text
  • The Social ABCs caregiver‐mediated intervention for toddlers with autism spectrum disorder: Feasibility, acceptability, and evidence of promise from a multisite study.
    Jessica A. Brian, Isabel M. Smith, Lonnie Zwaigenbaum, Wendy Roberts, Susan E. Bryson.
    Autism Research. December 21, 2015
    The Social ABCs is a parent‐mediated intervention for toddlers with suspected or confirmed autism spectrum disorder (ASD). We undertook a multi‐site pilot study to evaluate feasibility and acceptability, and to identify trends in child and parent behavior to inform future research using a larger sample and a rigorous research design. The program involved 12 weeks of parent coaching, followed by 12 weeks' implementation, and 3‐month follow‐up assessment for 20 parent‐toddler dyads (age range: 12–32 months). Parents successfully learned the techniques and rated the intervention as highly acceptable. Paired samples t‐tests revealed significant gains in children's functional communication (responsivity, initiations), and language gains (age‐equivalents on standardized measures) commensurate with typical developmental rates. Significant increases in shared smiling and social orienting also emerged, but were attenuated at follow‐up. Parents' fidelity was positively associated with child responsivity. Training parents as mediators is a feasible and highly acceptable approach that provides a potentially cost‐effective opportunity for intensive intervention at a very young age at the first signs of ASD risk. Child and parent gains in several key variables demonstrate the promise of this intervention. Autism Res 2016, 9: 899–912. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    December 21, 2015   doi: 10.1002/aur.1582   open full text
  • Subregional differences in intrinsic amygdala hyperconnectivity and hypoconnectivity in autism spectrum disorder.
    Natalia M. Kleinhans, Maya A. Reiter, Emily Neuhaus, Greg Pauley, Nathalie Martin, Stephen Dager, Annette Estes.
    Autism Research. December 15, 2015
    The amygdala is a complex structure with distinct subregions and dissociable functional networks. The laterobasal subregion of the amygdala is hypothesized to mediate the presentation and severity of autism symptoms, although very little data are available regarding amygdala dysfunction at the subregional level. In this study, we investigated the relationship between abnormal amygdalar intrinsic connectivity, autism symptom severity, and anxiety and depressive symptoms. We collected resting state fMRI data on 31 high functioning adolescents and adults with autism spectrum disorder and 38 typically developing (TD) controls aged 14–45. Twenty‐five participants with ASD and 28 TD participants were included in the final analyses. ASD participants were administered the Autism Diagnostic Interview–Revised and the Autism Diagnostic Observation Schedule. Adult participants were administered the Beck Depression Inventory II and the Beck Anxiety Inventory. Functional connectivity analyses were conducted from three amygdalar subregions: centromedial (CM), laterobasal (LB) and superficial (SF). In addition, correlations with the behavioral measures were tested in the adult participants. In general, the ASD group showed significantly decreased connectivity from the LB subregion and increased connectivity from the CM and SF subregions compared to the TD group. We found evidence that social symptoms are primarily associated with under‐connectivity from the LB subregion whereas over‐connectivity and under‐connectivity from the CM, SF and LB subregions are related to co‐morbid depression and anxiety in ASD, in brain regions that were distinct from those associated with social dysfunction, and in different patterns than were observed in mildly symptomatic TD participants. Our findings provide new evidence for functional subregional differences in amygdala pathophysiology in ASD. Autism Res 2016, 9: 760–772. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    December 15, 2015   doi: 10.1002/aur.1589   open full text
  • Using the brief observation of social communication change (BOSCC) to measure autism‐specific development.
    Janina Kitzerow, Karoline Teufel, Christian Wilker, Christine M. Freitag.
    Autism Research. December 08, 2015
    To date no reliable and objective, change sensitive instrument for autistic symptoms is available. The brief observation of social communication change (BOSCC) was specifically developed to measure change of core autistic symptoms, for example, for use as outcome measure in early intervention trials. This study investigated quality criteria of a preliminary research version of the BOSCC in N = 21 children with autism spectrum disorder (ASD) who had participated for 1 year in the Frankfurt early intervention program (FFIP). BOSCC rating was done on play based ADOS video scenes. Inter‐rater agreement on the BOSCC average total was very high. The BOSCC showed a significant decrease of autistic symptoms after 1 year with a medium effect size. Symptom specific improvements were captured by the social communication subscale and most single items. The BOSCC showed comparable change sensitivity to other autism specific instruments. Future studies should focus on the finalized BOSCC version, and replicate findings in a larger sample. Autism Res 2016, 9: 940–950. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    December 08, 2015   doi: 10.1002/aur.1588   open full text
  • Looking, seeing and believing in autism: Eye movements reveal how subtle cognitive processing differences impact in the social domain.
    Valerie Benson, Monica S. Castelhano, Philippa L. Howard, Nida Latif, Keith Rayner.
    Autism Research. November 28, 2015
    Adults with High Functioning Autism Spectrum Disorders (ASD) viewed scenes with people in them, while having their eye movements recorded. The task was to indicate, using a button press, whether the pictures were normal, or in some way weird or odd. Oddities in the pictures were categorized as violations of either perceptual or social norms. Compared to a Typically Developed (TD) control group, the ASD participants were equally able to categorize the scenes as odd or normal, but they took longer to respond. The eye movement patterns showed that the ASD group made more fixations and revisits to the target areas in the odd scenes compared with the TD group. Additionally, when the ASD group first fixated the target areas in the scenes, they failed to initially detect the social oddities. These two findings have clear implications for processing difficulties in ASD for the social domain, where it is important to detect social cues on‐line, and where there is little opportunity to go back and recheck possible cues in fast dynamic interactions. Autism Res 2016, 9: 879–887. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    November 28, 2015   doi: 10.1002/aur.1580   open full text
  • Stability of diagnostic assessment for autism spectrum disorder between 18 and 36 months in a high‐risk cohort.
    Lonnie Zwaigenbaum, Susan E. Bryson, Jessica Brian, Isabel M. Smith, Wendy Roberts, Peter Szatmari, Caroline Roncadin, Nancy Garon, Tracy Vaillancourt.
    Autism Research. November 27, 2015
    Children with autism spectrum disorder (ASD) are diagnosed, on average, around the age of 4 years. However, previous research has shown that the diagnosis can be made as early as 2 years, and that if the child is seen a year or more later, it is highly likely that the diagnosis will be confirmed. In this study, to examine whether diagnoses made as early as 18 months of age are also “stable,” we followed a group of younger siblings of children with ASD (who are known to be at higher risk). We also examined whether the age of ASD diagnosis within this high‐risk group was related to the severity of children's ASD symptoms or developmental delays. Participants (n = 381) were seen at three ages: 18 months, 24 months, and 3 years. ASD symptoms, general development, and adaptive functioning were assessed at each time point. Twenty‐three children were diagnosed with ASD at 18 months and a total of 61 at 24 months. Of these diagnoses, 19/23 (82.6%) and 56/61 (91.8%), respectively, were confirmed independently at 3 years. However, 45 children were diagnosed with ASD at 3 years who had not been identified at earlier visits. Children diagnosed at 18 months, in comparison to those diagnosed at 24 months, had less advanced language and adaptive skills at 18 months. Children not diagnosed with ASD until 3 years, compared with those diagnosed earlier, had more advanced language and adaptive skills, and milder ASD symptoms. Autism Res 2016, 9: 790–800. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    November 27, 2015   doi: 10.1002/aur.1585   open full text
  • The developmental trajectory of contrast sensitivity in autism spectrum disorder.
    Jacalyn Guy, Laurent Mottron, Claude Berthiaume, Armando Bertone.
    Autism Research. November 27, 2015
    Autism Spectrum Disorder (ASD) is characterized by a detail‐driven visual processing strategy, evidence for which has been based largely on cross‐sectional studies in small participant groups of limited age ranges. It is therefore unknown when sensitivity to detailed information emerges and develops in ASD. Contrast sensitivity to sinusoidal gratings of different spatial frequencies (0.5, 1, 2, 4, and 8 cycles per degree (cpd)) was measured for 34 participants with ASD and 55 typically developing participants (aged 6–16 years). Cross‐sectional, developmental trajectories were constructed to examine within and between group differences across the range of spatial frequencies tested. Developmental trajectories indicated that sensitivity across low (i.e., 0.5 and 1 cpd) and mid (2 and 4 cpd) spatial frequencies varied by chronological age within each group, with mid frequencies developing at a more significant rate than low frequencies. There was no overall difference between groups in terms of the relationship of sensitivity and age across spatial frequencies, yet the ASD group had an overall lower level of sensitivity. Closer examination revealed that the youngest participants with ASD had a reduced sensitivity for mid frequencies. Moreover, the ASD group showed a statistically significant developmental relationship at 8 cpd, which suggests that a trend for increased sensitivity to early detailed information may manifest beyond the ages tested. These findings demonstrate a differential development of contrast sensitivity for spatial frequencies in ASD and underscore the need to better identify what drives such differences in the “building blocks” of visual perception. Autism Res 2016, 9: 866–878. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    November 27, 2015   doi: 10.1002/aur.1579   open full text
  • The sensitivity and specificity of the social communication questionnaire for autism spectrum with respect to age.
    Lucy Barnard‐Brak, Adam Brewer, Steven Chesnut, David Richman, Anna Marie Schaeffer.
    Autism Research. November 26, 2015
    The age neutrality of the Social Communication Questionnaire (SCQ) was examined as a common screener for ASD. Mixed findings have been reported regarding the recommended cutoff score's ability to accurately classify an individual as at‐risk for autism spectrum disorder (ASD) (sensitivity) versus accurately classifying an individual as not at‐risk for ASD (specificity). With a sample from the National Database for Autism Research, this study examined the SCQ's sensitivity versus specificity. Analyses indicated that the actual sensitivity and specificity scores were lower than initially reported by the creators of the SCQ. Autism Res 2016, 9: 838–845. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    November 26, 2015   doi: 10.1002/aur.1584   open full text
  • Biochemistry of the cingulate cortex in autism: An MR spectroscopy study.
    Lauren E. Libero, Meredith A. Reid, David M. White, Nouha Salibi, Adrienne C. Lahti, Rajesh K. Kana.
    Autism Research. November 03, 2015
    Neuroimaging studies have uncovered structural and functional alterations in the cingulate cortex in individuals with autism spectrum disorders (ASD). Such abnormalities may underlie neurochemical imbalance. In order to characterize the neurochemical profile, the current study examined the concentration of brain metabolites in dorsal ACC (dACC) and posterior cingulate cortex (PCC) in high‐functioning adults with ASD. Twenty high‐functioning adults with ASD and 20 age‐and‐IQ‐matched typically developing (TD) peers participated in this Proton magnetic resonance spectroscopy (1H‐MRS) study. LCModel was used in analyzing the spectra to measure the levels of N‐Acetyl aspartate (NAA), choline (Cho), creatine (Cr), and glutamate/glutamine (Glx) in dACC and PCC. Groups were compared using means for the ratio of each metabolite to their respective Cr levels as well as on absolute internal‐water‐referenced measures of each metabolite. There was a significant increase in Cho in PCC for ASD adults, with a marginal increase in dACC. A reduction in NAA/Cr in dACC was found in ASD participants, compared to their TD peers. No significant differences in Glx/Cr or Cho/Cr were found in dACC. There were no statistically significant group differences in the absolute concentration of NAA, Cr, Glx, or NAA/Cr, Cho/Cr, and Glx/Cr in the PCC. Differences in the metabolic properties of dACC compared to PCC were also found. Results of this study provide evidence for possible cellular and metabolic differences in the dACC and PCC in adults with ASD. This may suggest neuronal dysfunction in these regions and may contribute to the neuropathology of ASD. Autism Res 2016, 9: 643–657. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    November 03, 2015   doi: 10.1002/aur.1562   open full text
  • Altered kynurenine pathway metabolism in autism: Implication for immune‐induced glutamatergic activity.
    Chai K. Lim, Musthafa M. Essa, Roberta de Paula Martins, David B. Lovejoy, Ayse A. Bilgin, Mostafa I. Waly, Yahya M. Al‐Farsi, Marwan Al‐Sharbati, Mohammed A. Al‐Shaffae, Gilles J. Guillemin.
    Autism Research. October 24, 2015
    Dysfunction of the serotoninergic and glutamatergic systems is implicated in the pathogenesis of autism spectrum disorder (ASD) together with various neuroinflammatory mediators. As the kynurenine pathway (KP) of tryptophan degradation is activated in neuroinflammatory states, we hypothesized that there may be a link between inflammation in ASD and enhanced KP activation resulting in reduced serotonin synthesis from tryptophan and production of KP metabolites capable of modulating glutamatergic activity. A cross‐sectional study of 15 different Omani families with newly diagnosed children with ASD (n = 15) and their age‐matched healthy siblings (n = 12) was designed. Immunological profile and the KP metabolic signature were characterized in the study participants. Our data indicated that there were alterations to the KP in ASD. Specifically, increased production of the downstream metabolite, quinolinic acid, which is capable of enhancing glutamatergic neurotransmission was noted. Correlation studies also demonstrated that the presence of inflammation induced KP activation in ASD. Until now, previous studies have failed to establish a link between inflammation, glutamatergic activity, and the KP. Our findings also suggest that increased quinolinic acid may be linked to 16p11.2 mutations leading to abnormal glutamatergic activity associated with ASD pathogenesis and may help rationalize the efficacy of sulforaphane treatment in ASD. Autism Res 2016, 9: 621–631. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 24, 2015   doi: 10.1002/aur.1565   open full text
  • The motivation for special interests in individuals with autism and controls: Development and validation of the special interest motivation scale.
    Rachel Grove, Ilona Roth, Rosa A. Hoekstra.
    Autism Research. October 24, 2015
    Clinical observations and first person accounts of living with autism suggest that individuals with autism are highly motivated to engage in special interests, and that these interests remain important throughout life. Previous research assessing special interests has mainly focused on parental reports of children with autism spectrum conditions (ASC). To better understand the significance of and motivations for engaging in special interests it is essential to use self‐report ratings. This paper aims to systematically explore the motivations for engagement in special interests, and whether these differ in adults with ASC, first‐degree relatives and general population controls. The Special Interest Motivation Scale (SIMS) was developed to assess motivation to engage in special interests. The internal structure of this scale was evaluated using factor analysis, and mean scores on the SIMS factors were subsequently compared across individuals with autism, parents and general population controls. Factor analysis indicated a 20‐item SIMS containing five factors assessing Personal life values and goals; Intrinsic interest and knowledge; Prestige; Engagement and “flow” and Achievement. Individuals with autism were more motivated by Intrinsic interest and knowledge and by Engagement and flow than controls. The 20‐item SIMS is a quick to administer measure that provides a reliable description of motivation to engage in special interests. This study indicates that individuals with ASC are highly motivated to engage in their special interest, and are more motivated than controls by intrinsic motivational factors, some of which are associated with positive affect. This has implications for research and clinical practice. Autism Res 2016, 9: 677–688. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 24, 2015   doi: 10.1002/aur.1560   open full text
  • Prolonged auditory brainstem responses in infants with autism.
    Oren Miron, Daphne Ari‐Even Roth, Lidia V. Gabis, Yael Henkin, Shahar Shefer, Ilan Dinstein, Ronny Geva.
    Autism Research. October 19, 2015
    Numerous studies have attempted to identify early physiological abnormalities in infants and toddlers who later develop autism spectrum disorder (ASD). One potential measure of early neurophysiology is the auditory brainstem response (ABR), which has been reported to exhibit prolonged latencies in children with ASD. We examined whether prolonged ABR latencies appear in infancy, before the onset of ASD symptoms, and irrespective of hearing thresholds. To determine how early in development these differences appear, we retrospectively examined clinical ABR recordings of infants who were later diagnosed with ASD. Of the 118 children in the participant pool, 48 were excluded due to elevated ABR thresholds, genetic aberrations, or old testing age, leaving a sample of 70 children: 30 of which were tested at 0–3 months, and 40 were tested at toddlerhood (1.5–3.5 years). In the infant group, the ABR wave‐V was significantly prolonged in those who later developed ASD as compared with case‐matched controls (n = 30). Classification of infants who later developed ASD and case‐matched controls using this measure enabled accurate identification of ASD infants with 80% specificity and 70% sensitivity. In the group of toddlers with ASD, absolute and interpeak latencies were prolonged compared to clinical norms. Findings indicate that ABR latencies are significantly prolonged in infants who are later diagnosed with ASD irrespective of their hearing thresholds; suggesting that abnormal responses might be detected soon after birth. Further research is needed to determine if ABR might be a valid marker for ASD risk. Autism Res 2016, 9: 689–695. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    October 19, 2015   doi: 10.1002/aur.1561   open full text
  • Assessment of sleep problems and related risk factors observed in Turkish children with Autism spectrum disorders.
    Tuba Mutluer, Sevcan Karakoc Demirkaya, Osman Abali.
    Autism Research. October 13, 2015
    Sleep problems are common and difficult to manage in children with autism spectrum disorders (ASD). Another major adverse impact of sleep problems is that they exacerbate behavioral problems. To assess sleep problems and possible behavioral risk factors in detail, we aimed to compare sleep habits of children with ASD, with healthy children. The relationship between sleep difficulties and concomitant behavioral problems such as repetitive behaviors, hyperactivity, and social withdrawal were also examined. Hundred and seventeen children and adolescents including 64 with the diagnosis of ASD and 53 healthy subjects were enrolled in the study. Diagnostic Interview for ASD was performed according to DSM‐IV‐TR. Socio‐demographical data form and childhood autism rating scale were filled by researchers. Aberrant behavior checklist (ABC), child behavior checklist and pediatric sleep questionnaire (PSQ) were completed by the parents of the children. Children with ASD had higher frequency of sleep problems, snoring, breathing problems, behavioral problems compared with healthy children (for all parameters; P < 0.001). A positive correlation was identified between the total score of PSQ and the total score of ABC (P < 0.05, Spearman correlation coefficient: 0.347). Sleep latency was prolonged in children with ASD compared with healthy subjects (P < 0.001). In accordance with the current literature, children with ASD were subject to sleep problems significantly more than the control group. Identified risk factors for sleep problems in ASD children were behavioral factors such as stereotypies, self‐mutilation, hyperactivity, and social withdrawal. Autism Res 2016, 9: 536–542. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 13, 2015   doi: 10.1002/aur.1542   open full text
  • Identifying diagnostically‐relevant resting state brain functional connectivity in the ventral posterior complex via genetic data mining in autism spectrum disorder.
    Philip R. Baldwin, Kaylah N. Curtis, Michelle A. Patriquin, Varina Wolf, Humsini Viswanath, Chad Shaw, Yasunari Sakai, Ramiro Salas.
    Autism Research. October 09, 2015
    Exome sequencing and copy number variation analyses continue to provide novel insight to the biological bases of autism spectrum disorder (ASD). The growing speed at which massive genetic data are produced causes serious lags in analysis and interpretation of the data. Thus, there is a need to develop systematic genetic data mining processes that facilitate efficient analysis of large datasets. We report a new genetic data mining system, ProcessGeneLists and integrated a list of ASD‐related genes with currently available resources in gene expression and functional connectivity of the human brain. Our data‐mining program successfully identified three primary regions of interest (ROIs) in the mouse brain: inferior colliculus, ventral posterior complex of the thalamus (VPC), and parafascicular nucleus (PFn). To understand its pathogenic relevance in ASD, we examined the resting state functional connectivity (RSFC) of the homologous ROIs in human brain with other brain regions that were previously implicated in the neuro‐psychiatric features of ASD. Among them, the RSFC of the VPC with the medial frontal gyrus (MFG) was significantly more anticorrelated, whereas the RSFC of the PN with the globus pallidus was significantly increased in children with ASD compared with healthy children. Moreover, greater values of RSFC between VPC and MFG were correlated with severity index and repetitive behaviors in children with ASD. No significant RSFC differences were detected in adults with ASD. Together, these data demonstrate the utility of our data‐mining program through identifying the aberrant connectivity of thalamo‐cortical circuits in children with ASD. Autism Res 2016, 9: 553–562. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 09, 2015   doi: 10.1002/aur.1559   open full text
  • School‐age outcomes of infants at risk for autism spectrum disorder.
    Meghan Miller, Ana‐Maria Iosif, Gregory S. Young, Monique Hill, Elise Phelps Hanzel, Ted Hutman, Scott Johnson, Sally Ozonoff.
    Autism Research. October 09, 2015
    Studies of infants at risk for autism spectrum disorder (ASD) have proliferated, but few of these samples have been followed longer‐term. We conducted a follow‐up study, at age 5.5–9 years, of younger siblings of children with ASD (high‐risk group, n = 79) or typical development (low‐risk group, n = 60), originally recruited as infants. Children with ASD were excluded because of the focus on understanding the range of non‐ASD outcomes among high‐risk siblings. Using examiner ratings, parent ratings, and standardized assessments, we evaluated differences in clinical outcomes, psychopathology symptoms, autism symptoms, language skills, and nonverbal cognitive abilities. After adjusting for covariates, the high‐risk group had increased odds of any clinically elevated/impaired score across measures relative to the low‐risk group (43% vs. 12%, respectively). The high‐risk group also had increased odds of examiner‐rated Clinical Concerns (CC) outcomes (e.g., ADHD concerns, broader autism phenotype, speech‐language difficulties, anxiety/mood problems, learning problems) relative to the low‐risk group (38% vs. 13%, respectively). The high‐risk group with CC outcomes had higher parent‐reported psychopathology and autism symptoms, and lower directly‐assessed language skills, than the Low‐Risk Typically Developing (TD) and High‐Risk TD groups, which did not differ. There were no differences in nonverbal cognitive skills. For some in the high‐risk group, clinical concerns persisted from early childhood, whereas for others clinical concerns were first evident at school‐age. Results suggest continued vulnerability in at least a subgroup of school‐age children with a family history of ASD and suggest that this population may benefit from continued screening and monitoring into the school‐age years. Autism Res 2016, 9: 632–642. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 09, 2015   doi: 10.1002/aur.1572   open full text
  • Prevalence of School Bullying Among Youth with Autism Spectrum Disorders: A Systematic Review and Meta‐Analysis.
    Christophe Maïano, Claude L. Normand, Marie‐Claude Salvas, Grégory Moullec, Annie Aimé.
    Autism Research. October 09, 2015
    The true extent of school bullying among youth with autism spectrum disorders (ASD) remains an underexplored area. The purpose of this meta‐analysis is to: (a) assess the proportion of school‐aged youth with ASD involved in school bullying as perpetrators, victims or both; (b) examine whether the observed prevalence estimates vary when different sources of heterogeneity related to the participants' characteristics and to the assessment methods are considered; and (c) compare the risk of school bullying between youth with ASD and their typically developing (TD) peers. A systematic literature search was performed and 17 studies met the inclusion criteria. The resulting pooled prevalence estimate for general school bullying perpetration, victimization and both was 10%, 44%, and 16%, respectively. Pooled prevalence was also estimated for physical, verbal, and relational school victimization and was 33%, 50%, and 31%, respectively. Moreover, subgroup analyses showed significant variations in the pooled prevalence by geographic location, school setting, information source, type of measures, assessment time frame, and bullying frequency criterion. Finally, school‐aged youth with ASD were found to be at greater risk of school victimization in general, as well as verbal bullying, than their TD peers. Autism Res 2016, 9: 601–615. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 09, 2015   doi: 10.1002/aur.1568   open full text
  • Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm.
    Alexandra M. Ure, Karli Treyvaud, Deanne K. Thompson, Leona Pascoe, Gehan Roberts, Katherine J. Lee, Marc L. Seal, Elisabeth Northam, Jeanie L. Cheong, Rod W. Hunt, Terrie Inder, Lex W. Doyle, Peter J. Anderson.
    Autism Research. October 07, 2015
    Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term‐born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy‐two VP children (<30 weeks' gestation or <1250 g birth weight) underwent structural brain MR scans at term equivalent age (TEA; 40 weeks' gestation ±2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2016, 9: 543–552. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 07, 2015   doi: 10.1002/aur.1558   open full text
  • Development of Planning in Children with High‐Functioning Autism Spectrum Disorders and/or Attention Deficit/Hyperactivity Disorder.
    Josef M. Unterrainer, Reinhold Rauh, Benjamin Rahm, Jochen Hardt, Christoph P. Kaller, Christoph Klein, Mirjam Paschke‐Müller, Monica Biscaldi.
    Autism Research. October 07, 2015
    Planning impairment is often observed in children with high‐functioning autism spectrum disorders (ASD), but attempts to differentiate planning in ASD from children with attention deficit hyperactivity disorder (ADHD) and typically developing children (TD) have yielded inconsistent results. This study examined differences between these groups by focusing on development and analyzing performance in searching ahead several steps (“search depth”) in addition to commonly used global performance measures in planning. A cross‐sectional consecutive sample of 83 male patients (6–13 years), subgrouped as ASD without (ASD−, n = 18) or with comorbid ADHD (ASD+, n = 23), ADHD only (n = 42) and n = 42 TD children (6–13 years) were tested with the Tower‐of‐London‐task. For global performance, ASD+ showed the lowest accuracy in younger children, but similar performance as TD at older ages, suggesting delayed development. Typically, a prolongation of planning time with increasing problem difficulty is observed in older children as compared to younger children. Here, this was most pronounced in ASD−, but under‐expressed in ADHD. In contrast to global performance, effects of search depth were independent of age. ASD−, but not ASD+, showed increased susceptibility to raised demands on mentally searching ahead, along with the longest planning times. Thus, examining both global and search depth performance across ages revealed discernible patterns of planning between groups. Notably, the potentially detrimental impact of two diagnosed disorders does not add up in ASD+ in this task. Rather, our results suggest paradoxical enhancement of performance, ostensibly attributable to disruption of behavioral rigidity through increased impulsivity, which did not take place in ASD−. Autism Res 2016, 9: 739–751. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 07, 2015   doi: 10.1002/aur.1574   open full text
  • Spontaneous Facial Mimicry is Modulated by Joint Attention and Autistic Traits.
    Janina Neufeld, Christina Ioannou, Sebastian Korb, Leonhard Schilbach, Bhismadev Chakrabarti.
    Autism Research. October 07, 2015
    Joint attention (JA) and spontaneous facial mimicry (SFM) are fundamental processes in social interactions, and they are closely related to empathic abilities. When tested independently, both of these processes have been usually observed to be atypical in individuals with autism spectrum conditions (ASC). However, it is not known how these processes interact with each other in relation to autistic traits. This study addresses this question by testing the impact of JA on SFM of happy faces using a truly interactive paradigm. Sixty‐two neurotypical participants engaged in gaze‐based social interaction with an anthropomorphic, gaze‐contingent virtual agent. The agent either established JA by initiating eye contact or looked away, before looking at an object and expressing happiness or disgust. Eye tracking was used to make the agent's gaze behavior and facial actions contingent to the participants' gaze. SFM of happy expressions was measured by Electromyography (EMG) recording over the Zygomaticus Major muscle. Results showed that JA augments SFM in individuals with low compared with high autistic traits. These findings are in line with reports of reduced impact of JA on action imitation in individuals with ASC. Moreover, they suggest that investigating atypical interactions between empathic processes, instead of testing these processes individually, might be crucial to understanding the nature of social deficits in autism. Autism Res 2016, 9: 781–789. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    October 07, 2015   doi: 10.1002/aur.1573   open full text
  • Slow intestinal transit contributes to elevate urinary p‐cresol level in Italian autistic children.
    Stefano Gabriele, Roberto Sacco, Laura Altieri, Cristina Neri, Andrea Urbani, Carmela Bravaccio, Maria Pia Riccio, Maria Rosaria Iovene, Francesca Bombace, Laura De Magistris, Antonio M. Persico.
    Autism Research. October 06, 2015
    The uremic toxin p‐cresol (4‐methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol‐producing bacteria present in the gut lumen. Elevated p‐cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p‐cresol in ASD. Urinary p‐cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile‐derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p‐cresol concentration (P < 0.05). No association was found with presence of Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability (P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD child was found to carry C. difficile in the gut or to release toxin A/B in the feces. In conclusion, urinary p‐cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2016, 9: 752–759. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 06, 2015   doi: 10.1002/aur.1571   open full text
  • Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies.
    Michael W. Nestor, Andre W. Phillips, Elena Artimovich, Jonathan E. Nestor, John P. Hussman, Gene J. Blatt.
    Autism Research. October 01, 2015
    Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental condition. Symptoms of ASD cover the spectrum from mild qualitative differences in social interaction to severe communication and social and behavioral challenges that require lifelong support. Attempts at understanding the pathophysiology of ASD have been hampered by a multifactorial etiology that stretches the limits of current behavioral and cell based models. Recent progress has implicated numerous autism‐risk genes but efforts to gain a better understanding of the underlying biological mechanisms have seen slow progress. This is in part due to lack of appropriate models for complete molecular and pharmacological studies. The advent of induced pluripotent stem cells (iPSC) has reinvigorated efforts to establish more complete model systems that more reliably identify molecular pathways and predict effective drug targets and candidates in ASD. iPSCs are particularly appealing because they can be derived from human patients and controls for research purposes and provide a technology for the development of a personalized treatment regimen for ASD patients. The pluripotency of iPSCs allow them to be reprogrammed into a number of CNS cell types and phenotypically screened across many patients. This quality is already being exploited in protocols to generate 2‐dimensional (2‐D) and three‐dimensional (3‐D) models of neurons and developing brain structures. iPSC models make powerful platforms that can be interrogated using electrophysiology, gene expression studies, and other cell‐based quantitative assays. iPSC technology has limitations but when combined with other model systems has great potential for helping define the underlying pathophysiology of ASD. Autism Res 2016, 9: 513–535. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 01, 2015   doi: 10.1002/aur.1570   open full text
  • Alexithymia in children with and without autism spectrum disorders.
    Cáit Griffin, Michael V. Lombardo, Bonnie Auyeung.
    Autism Research. October 01, 2015
    Alexithymia refers to pronounced difficulty in identifying and describing one's own emotions and is associated with an externally oriented focus of thinking. Alexithymia is known to be much more common in adults with autism spectrum disorders (ASD) compared with the typically developing (TD) adult population. However, we know very little about alexithymia in young children with ASD and advancing our understanding of this topic may be of critical clinical and translational importance. Here, we present the first study to examine alexithymia in children with ASD. We find that alexithymia is substantially elevated in ASD on both self‐ and parent‐report measures. Despite both measures being sensitive to on‐average group differentiation, we find no evidence of correlation between such measures, indicating that children and their parents may be using different sources of information. Parent‐rated alexithymia is also associated with increasing levels of autistic traits. Discrepancy between self and other alexithymia ratings are also associated with autistic traits, but only in ASD. These results underscore the idea that assessing alexithymia in ASD at younger ages may help identify important subgroups that have particular difficulties in the domain of emotion processing. Autism Res 2016, 9: 773–780. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    October 01, 2015   doi: 10.1002/aur.1569   open full text
  • Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context.
    A. Özge Sungur, Rainer K.W. Schwarting, Markus Wöhr.
    Autism Research. September 30, 2015
    Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation‐induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1−/− null mutant, Shank1+/− heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD‐related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1−/− pups vocalized less and displayed a delay in the typical inverted U‐shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype‐dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    September 30, 2015   doi: 10.1002/aur.1564   open full text
  • Keeping time in the brain: Autism spectrum disorder and audiovisual temporal processing.
    Ryan A. Stevenson, Magali Segers, Susanne Ferber, Morgan D. Barense, Stephen Camarata, Mark T. Wallace.
    Autism Research. September 24, 2015
    A growing area of interest and relevance in the study of autism spectrum disorder (ASD) focuses on the relationship between multisensory temporal function and the behavioral, perceptual, and cognitive impairments observed in ASD. Atypical sensory processing is becoming increasingly recognized as a core component of autism, with evidence of atypical processing across a number of sensory modalities. These deviations from typical processing underscore the value of interpreting ASD within a multisensory framework. Furthermore, converging evidence illustrates that these differences in audiovisual processing may be specifically related to temporal processing. This review seeks to bridge the connection between temporal processing and audiovisual perception, and to elaborate on emerging data showing differences in audiovisual temporal function in autism. We also discuss the consequence of such changes, the specific impact on the processing of different classes of audiovisual stimuli (e.g. speech vs. nonspeech, etc.), and the presumptive brain processes and networks underlying audiovisual temporal integration. Finally, possible downstream behavioral implications, and possible remediation strategies are outlined. Autism Res 2016, 9: 720–738. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    September 24, 2015   doi: 10.1002/aur.1566   open full text
  • Age‐related differences in cognition across the adult lifespan in autism spectrum disorder.
    Anne G. Lever, Hilde M. Geurts.
    Autism Research. September 02, 2015
    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age‐related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self‐report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20–79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age‐related effects on verbal memory, generativity, and ToM, while age‐related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age‐related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age‐related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666–676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    September 02, 2015   doi: 10.1002/aur.1545   open full text
  • Subgrouping siblings of people with autism: Identifying the broader autism phenotype.
    Emily Ruzich, Carrie Allison, Paula Smith, Peter Watson, Bonnie Auyeung, Howard Ring, Simon Baron‐Cohen.
    Autism Research. September 02, 2015
    We investigate the broader autism phenotype (BAP) in siblings of individuals with autism spectrum conditions (ASC). Autistic traits were measured in typical controls (n = 2,000), siblings (n = 496), and volunteers with ASC (n = 2,322) using the Autism‐Spectrum Quotient (AQ), both self‐report and parent‐report versions. Using cluster analysis of AQ subscale scores, two sibling subgroups were identified for both males and females: a cluster of low‐scorers and a cluster of high‐scorers. Results show that while siblings as a group have intermediate levels of autistic traits compared to control individuals and participants with ASC, when examined on a cluster level, the low‐scoring sibling group is more similar to typical controls while the high‐scoring group is more similar to the ASC clinical group. Further investigation into the underlying genetic and epigenetic characteristics of these two subgroups will be informative in understanding autistic traits, both within the general population and in relation to those with a clinical diagnosis. Autism Res 2016, 9: 658–665. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research
    September 02, 2015   doi: 10.1002/aur.1544   open full text
  • Children with Autism Show Altered Autonomic Adaptation to Novel and Familiar Social Partners.
    Emily Neuhaus, Raphael A. Bernier, Theodore P. Beauchaine.
    Autism Research. August 25, 2015
    Social deficits are fundamental to autism spectrum disorder (ASD), and a growing body of research implicates altered functioning of the autonomic nervous system (ANS), including both sympathetic and parasympathetic branches. However, few studies have explored both branches concurrently in ASD, particularly within the context of social interaction. The current study investigates patterns of change in indices of sympathetic (pre‐ejection period; PEP) and parasympathetic (respiratory sinus arrhythmia; RSA) cardiac influence as boys (ages 8–11 years) with (N = 18) and without (N = 18) ASD engage in dyadic social interaction with novel and familiar social partners. Groups showed similar patterns of autonomic change during interaction with the novel partner, but differed in heart rate, PEP, and RSA reactivity while interacting with a familiar partner. Boys without ASD evinced decreasing sympathetic and increasing parasympathetic influence, whereas boys with ASD increased in sympathetic influence. Boys without ASD also demonstrated more consistent ANS responses across partners than those with ASD, with parasympathetic responding differentiating familiar and novel interaction partners. Finally, PEP slopes with a familiar partner correlated with boys' social skills. Implications include the importance of considering autonomic state during clinical assessment and treatment, and the potential value of regulation strategies as a complement to intervention programs aiming to support social cognition and behavior. Autism Res 2016, 9: 579–591. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    August 25, 2015   doi: 10.1002/aur.1543   open full text
  • Structural and functional correlates of a quantitative autistic trait measured using the social responsive scale in neurotypical male adolescents.
    Pei‐Chi Tu, Ju‐Wei Hsu, Chen‐Chia Lan, Chia‐Chien Liu, Tung‐Ping Su, Ying‐Sheue Chen.
    Autism Research. August 18, 2015
    Behaviors associated with autism spectrum disorder (ASD) have been suggested to be considered as quantitative traits. This study investigated the structural and functional correlates of autistic traits measured using the Social Responsiveness Scale (SRS) in neurotypical adolescents. Twenty‐six neurotypical male adolescents (12–18 years old) were recruited for this study and underwent structural and resting functional magnetic resonance image scanning, and intelligence quotient and SRS evaluations. We used the automated surface‐based method (FreeSurfer) to measure cortical thickness and seed‐based functional connectivity (FC) analysis to derive the FC map of the dorsal anterior cingulate (dACC). Brain‐wise regression analyses of cortical thickness and FC maps on SRS scores were performed using a general linear model. The results indicated that higher autistic trait ratings of total SRS scores were associated with a thinner cortex in the left insula, right insula, and right superior temporal gyrus. Furthermore, we observed that only higher scores of social awareness were correlated with increased FC between the dACC and right superior temporal gyrus and decreased FC between the dACC and right putamen and thalamus. These results indicated that a quantitative trait in social cognition is associated with structural and connectivity variations linked to ASD patients. Autism Res 2016, 9: 570–578. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    August 18, 2015   doi: 10.1002/aur.1535   open full text
  • A Meta‐Analysis of Imitation Abilities in Individuals With Autism Spectrum Disorders.
    Laura A. Edwards.
    Autism Research. May 23, 2014
    Although imitation impairments are often reported in individuals with autism spectrum disorders (ASD), previous work has not yet determined whether these impairments are significant, specific to ASD, and present across the entire spectrum. This report of 53 studies on imitation in ASD seeks to determine whether individuals with ASD show significant imitation deficits, the magnitude of these deficits, and whether they are specific to ASD. Using standard meta‐analytic techniques in a random‐effects model, the data reviewed suggest that individuals with ASD show deficits in imitation, performing on average 0.81 SDs below individuals without ASD on imitation tasks. This deficit was specific to the condition of having ASD. Moderator analyses revealed that the average Autism Diagnostic Observation Schedule (ADOS) scores of groups of ASD participants were significantly and strongly negatively associated with the imitation abilities of these subjects, but average participant IQ was not associated with imitation abilities. Study setting, novelty of actions, format of imitation tasks (live vs. not), number of actions to imitate, or verbal prompts were not found to significantly affect the sizes of the imitation differences between individuals with and without ASD. The manner in which imitation was operationalized, however, had significant effects on whether imitation deficits were found between individuals with and without ASD. In tests that measured imitation of both form and end points, participants with ASD showed significant deficits compared with those without ASD; on tests of end point emulation only, individuals with ASD showed no deficits. Autism Res 2014, ●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    May 23, 2014   doi: 10.1002/aur.1379   open full text
  • Emotion Regulation in Children and Adolescents With Autism Spectrum Disorder.
    Andrea C. Samson, Antonio Y. Hardan, Rebecca W. Podell, Jennifer M. Phillips, James J. Gross.
    Autism Research. May 23, 2014
    Emotion dysregulation is not a formal criterion for the diagnosis of autism spectrum disorder (ASD). However, parents and clinicians have long noted the importance of emotional problems in individuals with ASD (e.g. tantrums and “meltdowns”). In this study, 21 high‐functioning children and adolescents with ASD and 22 age and gender group‐matched typically developing (TD) controls completed a Reactivity and Regulation Situation Task. This task assesses emotional reactivity and spontaneous use of emotion regulation strategies (problem solving, cognitive reappraisal, avoidance, distraction, venting, suppression, and relaxation) in the context of age‐appropriate ambiguous and potentially threatening negative scenarios. After the concept of cognitive reappraisal was explained, the scenarios were presented again to participants, and they were prompted to use this strategy. Results indicated that individuals with ASD exhibited the same level of reactivity to negative stimuli as TD participants. Furthermore, youth with ASD had a different emotion regulation profile than TD individuals, characterized by a less frequent use of cognitive reappraisal and more frequent use of suppression. When prompted to use cognitive reappraisal, participants with ASD were less able to implement reappraisal, but benefitted from this strategy when they were able to generate a reappraisal. Findings from this study suggest that cognitive reappraisal strategies may be useful to children and adolescents with ASD. Therefore, the development of treatment programs that focus on enhancing the use of adaptive forms of emotion regulation might decrease emotional problems and optimize long‐term outcomes in youth with ASD. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    May 23, 2014   doi: 10.1002/aur.1387   open full text
  • Mapping Collaboration Networks in the World of Autism Research.
    Neal D. Goldstein, Helen Tager‐Flusberg, Brian K. Lee.
    Autism Research. May 21, 2014
    In the era of globalization and with the emergence of autism spectrum disorder as a global concern, the landscape of autism research has expanded to encompass much of the world. Here, we seek to provide an overview of the world of autism research, by documenting collaboration underlying the International Meeting for Autism Research (IMFAR), the pre‐eminent annual scientific meeting devoted to the presentation of the latest autism research. We analyzed published abstracts presented at IMFAR meetings, between 2008 and 2013, to determine patterns of collaboration. We described collaboration networks on the individual, institutional, and international levels, and visually depicted these results on spatial network maps. Consistent with findings from other scientific disciplines, we found that collaboration is correlated with research productivity. Collaborative hotspots of autism research throughout the years were clustered on the East and West coasts of the U.S., Canada, and northern Europe. In years when conferences were held outside of North America, the proportion of abstracts from Europe and Asia increased. While IMFAR has traditionally been dominated by a large North American presence, greater global representation may be attained by shifting meeting locations to other regions of the world. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    May 21, 2014   doi: 10.1002/aur.1393   open full text
  • Modest Impact on Risk for Autism Spectrum Disorder of Rare Copy Number Variants at 15q11.2, Specifically Breakpoints 1 to 2.
    Pauline Chaste, Stephan J. Sanders, Kommu N. Mohan, Lambertus Klei, Youeun Song, Michael T. Murtha, Vanessa Hus, Jennifer K. Lowe, A. Jeremy Willsey, Daniel Moreno‐De‐Luca, Timothy W. Yu, Eric Fombonne, Daniel Geschwind, Dorothy E. Grice, David H. Ledbetter, Catherine Lord, Shrikant M. Mane, Donna M. Martin, Eric M. Morrow, Christopher A. Walsh, James S. Sutcliffe, Matthew W. State, Christa Lese Martin, Bernie Devlin, Arthur L. Beaudet, Edwin H. Cook, Soo‐Jeong Kim.
    Autism Research. May 12, 2014
    The proximal region of chromosome 15 is one of the genomic hotspots for copy number variants (CNVs). Among the rearrangements observed in this region, CNVs from the interval between the common breakpoints 1 and 2 (BP1 and BP2) have been reported cosegregating with autism spectrum disorder (ASD). Although evidence supporting an association between BP1‐BP2 CNVs and autism accumulates, the magnitude of the effect of BP1‐BP2 CNVs remains elusive, posing a great challenge to recurrence‐risk counseling. To gain further insight into their pathogenicity for ASD, we estimated the penetrance of the BP1‐BP2 CNVs for ASD as well as their effects on ASD‐related phenotypes in a well‐characterized ASD sample (n = 2525 families). Transmission disequilibrium test revealed significant preferential transmission only for the duplicated chromosome in probands (20T:9NT). The penetrance of the BP1‐BP2 CNVs for ASD was low, conferring additional risks of 0.3% (deletion) and 0.8% (duplication). Stepwise regression analyses suggest a greater effect of the CNVs on ASD‐related phenotype in males and when maternally inherited. Taken together, the results are consistent with BP1‐BP2 CNVs as risk factors for autism. However, their effect is modest, more akin to that seen for common variants. To be consistent with the current American College of Medical Genetics guidelines for interpretation of postnatal CNV, the BP1‐BP2 deletion and duplication CNVs would probably best be classified as variants of uncertain significance (VOUS): they appear to have an impact on risk, but one so modest that these CNVs do not merit pathogenic status. Autism Res 2014, ●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    May 12, 2014   doi: 10.1002/aur.1378   open full text
  • Rumination and Perceived Impairment Associated With Depressive Symptoms in a Verbal Adolescent–Adult ASD Sample.
    Katherine Gotham, Somer L. Bishop, Steven Brunwasser, Catherine Lord.
    Autism Research. May 06, 2014
    The aim of this study was to examine the association between depressive symptoms and several psychosocial constructs (insight into autism symptoms, rumination, desire for social interaction, and satisfaction with social support) that may play a role in the development or maintenance of depression in verbally fluent adolescents and adults with ASD. Participants included 50 individuals with ASD and verbal IQ ≥ 70, aged 16–35 (sample size varied by measure). Elevated depressive symptoms on the Beck Depression Inventory, 2nd edition (BDI‐II), were associated with greater self‐perceived, autism‐related impairments (n = 48), greater rumination (n = 21), and lower perceived social support (n = 37). Rumination tended to moderate the association between self‐perceived autism symptoms and BDI‐II scores (n = 21), and was significantly associated with ASD‐related insistence on sameness behaviors (n = 18). An unexpected relationship between depressive features and social participation and motivation will need to be clarified by longitudinal research. These and similar findings contribute to our understanding of the phenomenology of depression in ASD, which is critical to the development of practical prevention and treatment. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    May 06, 2014   doi: 10.1002/aur.1377   open full text
  • Electrodermal and Behavioral Responses of Children With Autism Spectrum Disorders to Sensory and Repetitive Stimuli.
    Carolyn McCormick, David Hessl, Suzanne L. Macari, Sally Ozonoff, Cherie Green, Sally J. Rogers.
    Autism Research. April 30, 2014
    Parents frequently report that their children with autism spectrum disorders (ASD) respond atypically to sensory stimuli. Repetitive behaviors are also part of the ASD behavioral profile. Abnormal physiological arousal may underlie both of these symptoms. Electrodermal activity (EDA) is an index of sympathetic nervous system arousal. The goals of this study were twofold: (1) to pilot methods for collecting EDA data in young children and (2) to examine hypothesized relationships among EDA, and sensory symptoms and repetitive behaviors in children with ASD as compared with children with typical development. EDA was recorded on 54 young children with ASD and on 33 children with typical development (TD) during a protocol that included baseline, exposure to sensory and repetitive stimuli, and play. Parents completed standardized questionnaires regarding their child's sensory symptoms and repetitive behaviors. Frequency and type of repetitive behavior during play was coded offline. Comparisons between EDA data for ASD and TD groups indicated no significant between‐group differences in any measures. Parents of children with ASD reported more abnormal responses to sensory stimuli and more repetitive behaviors, but scores on these measures were not significantly correlated with EDA or with frequency of observed repetitive behaviors. Parent report of frequency and severity of sensory symptoms was significantly correlated with reports of repetitive behaviors in both groups. Although parents of children with ASD report high levels of sensory symptoms and repetitive behaviors, these differences are not related to measured EDA arousal or reactivity. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    April 30, 2014   doi: 10.1002/aur.1382   open full text
  • Testing the Extreme Male Brain Theory of Autism Spectrum Disorder in a Familial Design.
    Ingeborg Hauth, Yvette G. E. Bruijn, Wouter Staal, Jan K. Buitelaar, Nanda N. Rommelse.
    Autism Research. April 28, 2014
    Autism Spectrum Disorder (ASD) may be an extreme manifestation of some male‐typical traits in both neuroanatomy and cognition. Using the ratio of the second to fourth digit (2D:4D) and digit length as biomarkers of (pre‐ and postnatal) testosterone levels, examined was whether hypermasculinized digit ratios and/or lengths were familial traits in ASD and investigated their relation to sexually dimorphic cognitive abilities. 2D:4D ratios and digit lengths of 216 children with ASD, 202 unaffected siblings, and 360 parents were compared with those of 174 control children and their 146 parents. Generalized Estimation Equations, Generalized Linear Models, and Linear Mixed Models were used to investigate parent–offspring relationships and group differences. In ASD probands and their relatives alike, digit length relative to overall height was significantly increased in comparison to controls. No significant group differences were found between affected and unaffected subjects, or between males and females. Additionally, 2D:4D ratios increased with age. No (consistent) associations were found between 2D:4D ratio or digit lengths and systemizing and empathizing skills. The findings emphasize the role of familially based elevated pre‐ and postnatal testosterone levels in the liability for ASD, but challenge the use of 2D:4D ratio as a proxy of prenatal testosterone exposure solely. Given that many genes influence digit length, the exact mechanisms underlying a familial predisposition toward increased digit length in ASD are as yet unknown and needs to be explored in future studies. Autism Res 2014, ●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    April 28, 2014   doi: 10.1002/aur.1384   open full text
  • Intact Facial Adaptation in Autistic Adults.
    Richard Cook, Rebecca Brewer, Punit Shah, Geoffrey Bird.
    Autism Research. April 22, 2014
    Adaptation paradigms seek to bias subsequently viewed stimuli through prolonged exposure to an adapting stimulus, thereby giving rise to an aftereffect. Recent experiments have found that children with autism spectrum disorders (ASD) show reduced facial aftereffects, prompting some researchers to speculate that all individuals with ASD exhibit deficient facial adaptation. However, caution is required when generalizing findings from samples of children with ASD to the wider ASD population. The reduced facial aftereffects seen in child samples may instead reflect delayed or atypical developmental trajectories, whereby individuals with ASD are slower to develop adaptive mechanisms. In the present study, two experiments were conducted to determine whether high‐functioning adults with ASD also show diminished aftereffects for facial identity and expression. In Experiment 1, using a procedure that minimized the contribution of low‐level retinotopic adaptation, we observed substantial aftereffects comparable to those seen in matched controls, for both facial identity and expression. A similar pattern of results was seen in Experiment 2 using a revised procedure that increased the contribution of retinotopic adaptation to the facial aftereffects observed. That adults with autism can show robust facial aftereffects raises the possibility that group differences are seen only at particular points during development, and may not be a lifelong feature of the condition. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    April 22, 2014   doi: 10.1002/aur.1381   open full text
  • Are Urinary Porphyrins a Valid Diagnostic Biomarker of Autism Spectrum Disorder?
    Kerrie Shandley, David W. Austin, Jahar L. Bhowmik.
    Autism Research. April 22, 2014
    A fundamental challenge to the timely diagnosis of Autism Spectrum Disorder (ASD) is the reliance on the observation of a set of aberrant behavior. Consequently, the diagnostic process requires that the child reach an age where the behaviors would typically be exhibited. The identification of a reliable biological marker (biomarker) could be of considerable benefit to the diagnostic process. As a diagnostic biomarker, porphyrins present an attractive prospect as previous studies have reported consistent findings of children with ASD showing significant elevations in porphyrin levels in contrast to controls. Furthermore, there is some evidence that ASD severity may be associated with porphyrins, which would be a valuable characteristic of any ASD biomarker. Importantly, for practical use, porphyrins can be tested non‐invasively via a sample of urine. The present study sought to investigate whether porphyrin profiles can reliably be used to (a) differentiate ASD cases from healthy controls; and (b) predict ASD severity. The study compared the porphyrin levels of three groups of children aged 2–6 years: Group 1—children diagnosed with ASD (n = 70); Group 2—healthy, normally developing siblings of children diagnosed with ASD (n = 36); and Group 3—healthy, normally developing children with no known blood relative diagnosed with ASD (n = 54). The results of logistic regression analyses failed to find support for the hypotheses that porphyrin levels could be used as a valid tool to detect ASD cases or predict severity. Autism Res 2014 , ●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    April 22, 2014   doi: 10.1002/aur.1385   open full text
  • Gastrointestinal Dysfunction in Children With Autism Spectrum Disorders.
    Victor Kang, George C. Wagner, Xue Ming.
    Autism Research. April 21, 2014
    Gastrointestinal (GI) dysfunctions are frequently reported by parents of children with autism spectrum disorders (ASD) and have been recently recognized as a comorbid condition. However, the clinical significance of these GI dysfunctions remains to be delineated. This study describes the clinical characteristics, associated comorbid disorders, and endoscopic and colonoscopic evaluation of GI dysfunction in a cohort of 164 children with ASD evaluated at a pediatric neurology practice. Symptoms of GI dysfunction were prevalent: 49% of the children reported one or more chronic GI complaints, 22% exhibited diarrhea, 26% suffered from constipation. Furthermore 13% of the parents reported their children to suffer from bloating and/or being gassy and while 10% of the parents reported vomiting or gastroesophageal reflux problems. Similar rates of GI symptoms were reported among pre‐school and school‐aged children. Inflammation of the gut was found in 6 of the 12 subjects who underwent endoscopic and colonoscopic evaluations, however clinical symptoms did not predict the results of the evaluation. GI dysfunction was significantly associated with sleep disorders and food intolerance, but not with irritability or aggressiveness. In summary, GI dysfunction was prevalent in this cohort of children with ASD, observations consistent with the reports of parents and other clinicians. We conclude that the GI dysfunction in ASD requires proper evaluation and treatment. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    April 21, 2014   doi: 10.1002/aur.1386   open full text
  • Family‐Based Clinical Associations and Functional Characterization of the Serotonin 2A Receptor Gene (HTR2A) in Autism Spectrum Disorder.
    Ryan M. Smith, Wesley Banks, Emily Hansen, Wolfgang Sadee, Gail E. Herman.
    Autism Research. April 17, 2014
    The serotonin 2A receptor gene (HTR2A) harbors two functional single nucleotide polymorphisms (SNPs) that are frequent in populations of African and European descent; rs6311, which affects mRNA expression, and rs6314, which changes the amino acid sequence of the encoded protein and affects the signaling properties of the receptor. Multiple clinical associations support a role for these SNPs in cognitive and neuropsychiatric phenotypes, although studies in autism spectrum disorder (ASD) remain equivocal. Here, we tested transmission disequilibrium of rs6311 and rs6314 in a cohort of 158 ASD trios (simplex and multiplex), observing significant under‐transmission of the minor “A” allele of rs6311 to offspring with ASD (permuted P = 0.0004). Consistent with our previous findings in the dorsolateral prefrontal cortex of unaffected individuals, rs6311/A decreases expression of HTR2A mRNA with an extended 5′ untranslated region (UTR) in the frontopolar cortex in brain samples from 54 ASD patients and controls. Interpreting the clinical results in the context of our mRNA expression analysis, we speculate that any risk associated with rs6311 is conferred by greater expression of the long 5′UTR mRNA isoform. The current study corroborates earlier associations between rs6311 and ASD in a family study, supporting the hypothesis that rs6311 plays a modulatory role in ASD risk. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    April 17, 2014   doi: 10.1002/aur.1383   open full text
  • Propensity to Imitate in Autism Is Not Modulated by the Model's Gaze Direction: An Eye‐Tracking Study.
    Giacomo Vivanti, Cheryl Dissanayake.
    Autism Research. April 16, 2014
    Individuals with Autism Spectrum Disorder (ASD) show a diminished propensity to imitate others' actions, as well as a diminished sensitivity and responsivity to others' communicative cues, such as a direct gaze. However, it is not known whether failure to appreciate the communicative value of a direct gaze is associated with imitation abnormalities in this population. In this eye‐tracking study, we investigated how 25 preschoolers with ASD, compared with 25 developmental and chronological age‐matched children, imitate actions that are associated with a model's direct gaze versus averted gaze. We found that the model's direct gaze immediately prior to the demonstration increased the attention to the model and the propensity to imitate the demonstrated action in children without ASD. In contrast, preschoolers with ASD showed a similar propensity to look at the model's face and to imitate the demonstrated actions across the direct gaze and the averted gaze conditions. These data indicate that atypical imitation in ASD might be linked to abnormal processing of the model's communicative signals (such as a direct gaze) that modulate imitative behaviours in individuals without ASD. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    April 16, 2014   doi: 10.1002/aur.1376   open full text
  • Susceptibility to Distraction in Autism Spectrum Disorder: Probing the Integrity of Oscillatory Alpha‐Band Suppression Mechanisms.
    Jeremy W. Murphy, John J. Foxe, Joanna B. Peters, Sophie Molholm.
    Autism Research. March 27, 2014
    When attention is directed to one information stream over another, the brain can be configured in advance to selectively process the relevant stream and suppress potentially distracting inputs. One key mechanism of suppression is through the deployment of anticipatory alpha‐band (∼10 Hz) oscillatory activity, with greater alpha‐band power observed in cortical regions that will ultimately process the distracting stream. Atypical attention has been implicated in autism spectrum disorder (ASD), including greater interference by distracting task‐irrelevant inputs. Here we tested the integrity of these alpha‐band mechanisms in ASD using an intersensory attention task. Electroencephalography (EEG) was recorded while participants were cued on a trial‐by‐trial basis to selectively deploy attention to the visual or auditory modality in anticipation of a target within the cued modality. Whereas typically developing (TD) children showed the predicted alpha‐band modulation, with increased alpha‐band power over parieto‐occipital scalp when attention was deployed to the auditory compared with the visual modality, this differential pattern was entirely absent at the group level in the ASD cohort. Further, only the ASD group showed impaired performance due to the presence of task‐irrelevant sensory information. These data suggest that impaired modulation of alpha‐band activity plays a role in increased distraction from extraneous sensory inputs in ASD. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 27, 2014   doi: 10.1002/aur.1374   open full text
  • Autism Characteristics and Behavioural Disturbances in ∼ 500 Children with Down's Syndrome in England and Wales.
    Georgina Warner, Joanna Moss, Patrick Smith, Patricia Howlin.
    Autism Research. March 24, 2014
    Recent research shows that a significant minority of children with Down's syndrome (DS) also meet diagnostic criteria for an autism spectrum disorder (ASD). The present study investigated what proportion of children aged 6–15 years with a confirmed diagnosis of DS in England and Wales display autistic‐type behaviours, and explored the characteristics of this group of children. The Social Communication Questionnaire (SCQ) was used to screen for autism characteristics and the Strengths and Difficulties Questionnaire (SDQ) to explore behavioural difficulties. The proportion of children who met the cut‐off score for ASD on the SCQ (total score ≥ 15) was 37.7% (95% CI: 33.4–42.0%); for autism (total score ≥ 22) the proportion was 16.5% (95% CI: 13.2–19.8%). Children who met the cut‐off for ASD were significantly more likely to be reported as having emotional symptoms, conduct problems and hyperactivity on the SDQ than children who scored well below cut‐off (total score < 10). However, the profile of their autism characteristics on the SCQ was atypical compared with individuals with idiopathic ASD. The pervasiveness of ASD in children with DS in England and Wales is substantially higher than in the general population. These children also experience significantly greater behavioural problems than children with DS only. Early detection of autism characteristics is important for appropriate intervention. However, the unusual profile of autism characteristics in this group may affect the recognition of the disorder and hinder the implementation of appropriate interventions. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 24, 2014   doi: 10.1002/aur.1371   open full text
  • Classification of Children With Autism Spectrum Disorder by Sensory Subtype: A Case for Sensory‐Based Phenotypes.
    Alison E. Lane, Cynthia A. Molloy, Somer L. Bishop.
    Autism Research. March 17, 2014
    This study examines whether sensory differences can be used to classify meaningful subgroups of children with autism spectrum disorder (ASD). Caregivers of children with ASD aged 2–10 years (n = 228) completed the Short Sensory Profile. Model‐based cluster analysis was used to extract sensory subtypes. The relationship of these subtypes to age, gender, autism symptom severity, and nonverbal intelligence quotient (IQ) was further explored. Four distinct sensory subtypes were identified: (a) sensory adaptive; (b) taste smell sensitive; (c) postural inattentive; and (d) generalized sensory difference. The sensory subtypes differ from each other on two dimensions: (a) the severity of reported sensory differences; and (b) the focus of differences across auditory, taste, smell, vestibular and proprioceptive domains. Examination of the clinical features of each subtype reveals two possible mechanisms of sensory disturbance in autism: (a) sensory hyperreactivity; and (b) difficulties with multisensory processing. Further, the sensory subtypes are not well explained by other variables such as age, gender, IQ, and autism symptom severity. We conclude that classification of children using sensory differences offers a promising method by which to identify phenotypes in ASD. Sensory‐based phenotypes may be useful in identifying behavioral features responsive to specific interventions thereby improving intervention effectiveness. Further validation of the sensory‐based phenotypes by establishing neural and physiological correlates is recommended. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 17, 2014   doi: 10.1002/aur.1368   open full text
  • Prosodic Development in Middle Childhood and Adolescence in High‐Functioning Autism.
    Megan Lyons, Elizabeth Schoen Simmons, Rhea Paul.
    Autism Research. March 14, 2014
    The present study aims to investigate the perception and production of several domains of prosodic performance in a cross‐sectional sample of preadolescents and adolescents with and without high‐functioning autism (HFA). To look at the role of language abilities on prosodic performance, the HFA groups were subdivided based on “high” and “low” language performance on the Clinical Evaluation of Language Fundamentals‐Fourth Edition (CELF‐4) (Semel, Wiig, & Secord). Social and cognitive abilities were also examined to determine their relationship to prosodic performance. No significant differences were seen in prosody scores in the younger versus older subgroups in typically developing (TD) group with age‐appropriate language. There was small but significant improvement in performance with age in the groups with HFA. Comparing performance at each age level across diagnostic groups showed that preteens with HFA and higher language levels perform similarly to their TD peers on all prosodic tasks, whereas those with lower language skills scored significantly worse than both their higher language and TD peers when looking at composite perception and production findings. Teens with HFA showed no deficits on perception tasks; however, those with low language levels had difficulty on several production tasks when compared to the TD group. Regression analyses suggested that, for the preteen group with HFA, language was the strongest predictor of prosodic perception, whereas nonverbal IQ was most highly predictive of prosodic production. For adolescents with HFA, social skills significantly contributed to the prediction of prosodic perception and, along with language abilities, predicted prosodic production. Implications of these findings will be discussed. Autism Res 2014, 7: 181–196.. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 14, 2014   doi: 10.1002/aur.1355   open full text
  • A Deletion Involving CD38 and BST1 Results in a Fusion Transcript in a Patient With Autism and Asthma.
    Fabiola Ceroni, Angela Sagar, Nuala H. Simpson, Alex J.T. Gawthrope, Dianne F. Newbury, Dalila Pinto, Sunday M. Francis, Dorothy C. Tessman, Edwin H. Cook, Anthony P. Monaco, Elena Maestrini, Alistair T. Pagnamenta, Suma Jacob.
    Autism Research. March 13, 2014
    CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression—previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1‐CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister. Autism Res 2014, 7: 254–263. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 13, 2014   doi: 10.1002/aur.1365   open full text
  • The Association Between Social Cognition and Executive Functioning and Symptoms of Anxiety and Depression in Adolescents With Autism Spectrum Disorders.
    Matthew J. Hollocks, Catherine R.G. Jones, Andrew Pickles, Gillian Baird, Francesca Happé, Tony Charman, Emily Simonoff.
    Autism Research. March 12, 2014
    While high levels of anxiety and depression are now recognized as major co‐occurring problems in children and young people with an autism spectrum disorder (ASD), research examining possible associations with individual differences in neurocognitive functioning has been limited. This study included 90 adolescents with an ASD aged 14–16 years with a full‐scale IQ > 50. Using structural equation modeling, we examined the independent relationships between multiple measures of executive functioning and social cognition on severity of anxiety or depressive symptoms. Results indicated a significant association between poorer executive functioning and higher levels of anxiety, but not depression. In contrast, social cognition ability was not associated with either anxiety or depression. This study is the first to report significant associations between executive functions and anxiety in ASD. This may suggest that poor executive functioning is one factor associated with the high prevalence of anxiety disorder in children and adolescents with ASD. Autism Res 2014, 7: 216–228. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 12, 2014   doi: 10.1002/aur.1361   open full text
  • Electroencephalogram Coherence in Children With and Without Autism Spectrum Disorders: Decreased Interhemispheric Connectivity in Autism.
    Audrey M. Carson, Nicole M. G. Salowitz, Robert A. Scheidt, Bridget K. Dolan, Amy V. Van Hecke.
    Autism Research. March 12, 2014
    Electroencephalogram coherence was measured in children with autism spectrum disorders (ASD) and control children at baseline and while watching videos of a familiar and unfamiliar person reading a story. Coherence was measured between the left and right hemispheres of the frontal, parietal, and temporal‐parietal lobes (interhemispheric) and between the frontal and parietal lobes in each hemisphere (intrahemispheric). A data‐reduction technique was employed to identify the frequency (alpha) that yielded significant differences in video conditions. Children with ASD displayed reduced coherence at the alpha frequency between the left and right temporal‐parietal lobes in all conditions and reduced coherence at the alpha frequency between left and right frontal lobes during baseline. No group differences in intrahemispheric coherence at the alpha frequency emerged at the chosen statistical threshold. Results suggest decreased interhemispheric connectivity in frontal and temporal‐parietal regions in children with ASD compared to controls. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 12, 2014   doi: 10.1002/aur.1367   open full text
  • Autism‐Related Neuroligin‐3 Mutation Alters Social Behavior and Spatial Learning.
    Thomas C. Jaramillo, Shunan Liu, Ami Pettersen, Shari G. Birnbaum, Craig M. Powell.
    Autism Research. March 11, 2014
    Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome‐wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin‐3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin‐3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism‐associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Südhof laboratory, we reported that mice with an R451C substitution in neuroligin‐3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Südhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin‐3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore, we sought to replicate our findings in the neuroligin‐3 R451C point mutant knock‐in mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social deficits, enhanced spatial learning, and increased locomotor activity. These data extend our previous findings that NL3R451C mice exhibit autism‐relevant behavioral abnormalities and further suggest that different genetic backgrounds can modify this behavioral phenotype through epistatic genetic interactions. Autism Res 2014, 7: 264–272. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 11, 2014   doi: 10.1002/aur.1362   open full text
  • Emotion Regulation Patterns in Adolescents With High‐Functioning Autism Spectrum Disorder: Comparison to Typically Developing Adolescents and Association With Psychiatric Symptoms.
    Carla A. Mazefsky, Xenia Borue, Taylor N. Day, Nancy J. Minshew.
    Autism Research. March 07, 2014
    Autism spectrum disorder (ASD) is often associated with poor emotional control and psychopathology, such as anxiety and depression; however, little is known about the underlying mechanisms. Emotion regulation (ER) is a potential contributing factor, but there has been limited research on ER and its role in comorbid psychopathology in ASD. In this study, we compared self‐reported ER with self‐ and parent reports of psychopathology in 25 high‐functioning adolescents with ASD and 23 age‐ and Intelligence Quotient (IQ)‐matched typically developing controls. Contrary to expectations, both groups reported similar levels of adaptive, voluntary forms of ER (problem solving, acceptance, etc.). However, the ASD group reported significantly greater use of involuntary forms of ER that are typically maladaptive, including remaining focused on the stressor (e.g. rumination and emotional arousal) and shutting down (e.g. emotional numbing and being unable to think or act). Associations between ER and psychopathology were generally more robust using self‐report rather than parent report. For both groups, greater endorsement of involuntary ER strategies was associated with higher ratings of psychopathology, whereas voluntary ER strategies focused on changing or adapting to the situation were significantly associated with lower levels of psychopathology. The magnitude and direction of association between ER types and psychopathology were similar for measures of depression and anxiety. These findings can help guide the development of psychosocial treatments targeting dysfunctional ER in adolescents with ASD. Interventions focused on ER as a transdiagnostic process may be a more robust method to improve emotional control and decrease emotional distress in ASD than disorder‐specific interventions. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 07, 2014   doi: 10.1002/aur.1366   open full text
  • What and Why Understanding in Autism Spectrum Disorders and Williams Syndrome: Similarities and Differences.
    Laura Sparaci, Silvia Stefanini, Lidia D'Elia, Stefano Vicari, Giacomo Rizzolatti.
    Autism Research. March 06, 2014
    Children with autism spectrum disorders (ASD) and children with Williams syndrome (WS) show divergent social phenotypes, but also several similarities in their socio‐cognitive deficits. Cross‐syndrome direct comparisons could lead to a better understanding of mechanisms that determine deficits in social cognition in the two syndromes. A fundamental factor for social cognition is the ability to understand and predict others' actions (e.g. what action is being done and why it is being done when observing a goal‐related act). Here we compared the understanding of others' actions in children with ASD, WS and in children with typical development. Comprehension of what motor act was being done and of why it was being done was assessed with or without contextual cueing using a computer‐based task. The results showed that what understanding was impaired in the WS group, but not in the ASD group, which showed mental‐age appropriate performance. Why understanding was impaired in both experimental groups. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 06, 2014   doi: 10.1002/aur.1370   open full text
  • Prepotent Response Inhibition and Interference Control in Autism Spectrum Disorders: Two Meta‐Analyses.
    Hilde M. Geurts, Sanne F. W. M. Bergh, Laura Ruzzano.
    Autism Research. March 04, 2014
    There is a substantial amount of data providing evidence for, but also against the hypothesis that individuals with autism spectrum disorders (ASD) encounter inhibitory control deficits. ASD is often associated with interference control deficits rather than prepotent response inhibition. Moreover, the developmental trajectory for these inhibitory control processes is hypothesized to differ in ASD as compared to typical development. In efforts to gain a more comprehensive perspective of inhibition in ASD, separate quantitative analysis for prepotent response inhibition studies and interference control studies were conducted. Together, these two meta‐analyses included 41 studies with a combined sample size of 1,091 people with ASD (M age 14.8 years), and 1,306 typically developing (TD) controls (M age 13.8 years).The meta‐analyses indicated that individuals with ASD show increased difficulties in prepotent response inhibition (effect size 0.55) and in interference control (effect size 0.31). In addition, age was a relevant moderator for prepotent response inhibition but not for interference control. Exploratory analyses revealed that when IQ was taken into account, heterogeneity considerably decreased among interference control studies but not among prepotent response inhibition. In contrast to the general belief, both prepotent response inhibition and interference control problems were observed in individuals with ASD. However, a large variation between studies was also found. Therefore, there remain factors beyond inhibition type, age, or IQ that significantly influence inhibitory control performance among individuals with ASD. Autism Res 2014, ●●: ●●–●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    March 04, 2014   doi: 10.1002/aur.1369   open full text
  • Time Estimation Among Low‐Functioning Individuals With Autism Spectrum Disorders: Evidence of Poor Sensitivity to Variability of Short Durations.
    Darlene A. Brodeur, Cathryn Gordon Green, Heidi Flores, Jacob A. Burack.
    Autism Research. February 26, 2014
    Time estimation of short durations (under 1 sec) was examined in low‐functioning individuals with autism spectrum disorder (ASD) and typically developing (TD) children matched on mental age. Temporal bisection and generalization tasks were used to examine basic perceptual timing mechanisms. For both tasks, the participants with ASD demonstrated less sensitivity to variability in short durations than the TD children, adding to a growing body of literature suggesting deficits in timing exist for longer durations. The results highlight the need to examine multiple levels of processing of time‐related information from basic perceptual mechanisms to higher level cognitive mechanisms. Autism Res 2014, 7: 237–244. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    February 26, 2014   doi: 10.1002/aur.1364   open full text
  • Investigation of Maternal Genotype Effects in Autism by Genome‐Wide Association.
    Han Yuan, Joseph D. Dougherty.
    Autism Research. February 25, 2014
    Like most psychiatric disorders, autism spectrum disorders have both a genetic and an environmental component. While previous studies have clearly demonstrated the contribution of in utero (prenatal) environment on autism risk, most of them focused on transient environmental factors. Based on a recent sibling study, we hypothesized that environmental factors could also come from the maternal genome, which would result in persistent effects across siblings. In this study, the possibility of maternal genotype effects was examined by looking for common variants (single‐nucleotide polymorphisms or SNPs) in the maternal genome associated with increased risk of autism in children. A case/control genome‐wide association study was performed using mothers of probands as cases, and either fathers of probands or normal females as controls. Autism Genetic Resource Exchange and Illumina Genotype Control Database were used as our discovery cohort (n = 1616). The same analysis was then replicated on Simon Simplex Collection and Study of Addiction: Genetics and Environment datasets (n = 2732). We did not identify any SNP that reached genome‐wide significance (P < 10−8), and thus a common variant of large effect is unlikely. However, there was evidence for the possibility of a large number of alleles of effective size marginally below our power to detect. Autism Res 2014, 7: 245–253. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    February 25, 2014   doi: 10.1002/aur.1363   open full text
  • Age‐Related Changes in Conjunctive Visual Search in Children with and without ASD.
    Grace Iarocci, Kimberly Armstrong.
    Autism Research. February 20, 2014
    Visual‐spatial strengths observed among people with autism spectrum disorder (ASD) may be associated with increased efficiency of selective attention mechanisms such as visual search. In a series of studies, researchers examined the visual search of targets that share features with distractors in a visual array and concluded that people with ASD showed enhanced performance on visual search tasks. However, methodological limitations, the small sample sizes, and the lack of developmental analysis have tempered the interpretations of these results. In this study, we specifically addressed age‐related changes in visual search. We examined conjunctive visual search in groups of children with (n = 34) and without ASD (n = 35) at 7–9 years of age when visual search performance is beginning to improve, and later, at 10–12 years, when performance has improved. The results were consistent with previous developmental findings; 10‐ to 12‐year‐old children were significantly faster visual searchers than their 7‐ to 9‐year‐old counterparts. However, we found no evidence of enhanced search performance among the children with ASD at either the younger or older ages. More research is needed to understand the development of visual search in both children with and without ASD. Autism Res 2014, 7: 229–236. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    February 20, 2014   doi: 10.1002/aur.1359   open full text
  • Two to Ten Years: Developmental Trajectories of Joint Attention in Children With ASD Who Received Targeted Social Communication Interventions.
    Amanda C. Gulsrud, Gerhard S. Hellemann, Stephanny F.N. Freeman, Connie Kasari.
    Autism Research. February 18, 2014
    This study follows 40 children who were participants in a randomized controlled early intervention trial (Kasari et al.) from early childhood (2–5 years of age) to elementary school age (8–10 years). To fully utilize the available longitudinal data, the general linear mixed model was the primary analytical approach. The growth trajectories of joint attention skills (pointing, coordinated joint looking, and showing) and expressive language outcomes in these children were estimated based on five time points during the measurement period. The children were grouped by diagnosis at the last follow‐up (autism, autism spectrum disorder (ASD), no diagnosis) and by their original treatment group assignment (joint attention, symbolic play, control), and differences between these groups were evaluated. Results showed that joint attention skills of coordinated joint looking and showing increased over time, and pointing to share interest increased over the first year measured and decreased thereafter. These trajectories were influenced by both original treatment assignment and diagnostic status at follow‐up. In addition, a cross‐lagged panel analysis revealed a causal relationship between early pointing and later language development. This study highlights the longitudinal and developmental importance of measures of early core deficits in autism, and suggests that both treatment and ASD symptomatology may influence growth in these skills over time. Autism Res 2014, 7: 207–215. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    February 18, 2014   doi: 10.1002/aur.1360   open full text
  • Exploring the Role of Neural Mirroring in Children with Autism Spectrum Disorder.
    Lieselot Ruysschaert, Petra Warreyn, Jan R. Wiersema, Ann Oostra, Herbert Roeyers.
    Autism Research. February 10, 2014
    Investigating the underlying neural mechanisms of autism spectrum disorder (ASD) has recently been influenced by the discovery of mirror neurons. These neurons, active during both observation and execution of actions, are thought to play a crucial role in imitation and other social‐communicative skills that are often impaired in ASD. In the current electroencephalographic study, we investigated mu suppression, indicating neural mirroring in children with ASD between the ages of 24 and 48 months and age‐matched typically developing children, during observation of goal‐directed actions and non‐goal‐directed mimicked hand movements, as well as during action execution. Results revealed no significant group differences with significant central mu suppression in the ASD children and control children during both execution and observation of goal‐directed actions and during observation of hand movements. Furthermore, no significant correlations between mu suppression on one hand and quality of imitation, age, and social communication questionnaire scores on the other hand were found. These findings challenge the “broken mirror” hypothesis of ASD, suggesting that impaired neural mirroring is not a distinctive feature of ASD. Autism Res 2014, 7: 197– 206. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
    February 10, 2014   doi: 10.1002/aur.1339   open full text
  • Gut Permeability in Autism Spectrum Disorders.
    Neil Dalton, Susie Chandler, Charles Turner, Tony Charman, Andrew Pickles, Tom Loucas, Emily Simonoff, Peter Sullivan, Gillian Baird.
    Autism Research. December 12, 2013
    Objective To test whether gut permeability is increased in autism spectrum disorders (ASD) by evaluating gut permeability in a population‐derived cohort of children with ASD compared with age‐ and intelligence quotient‐matched controls without ASD but with special educational needs (SEN). Patients and Methods One hundred thirty‐three children aged 10–14 years, 103 with ASD and 30 with SEN, were given an oral test dose of mannitol and lactulose and urine collected for 6 hr. Gut permeability was assessed by measuring the urine lactulose/mannitol (L/M) recovery ratio by electrospray mass spectrometry‐mass spectrometry. The ASD group was subcategorized for comparison into those without (n = 83) and with (n = 20) regression. Results There was no significant difference in L/M recovery ratio (mean (95% confidence interval)) between the groups with ASD: 0.015 (0.013–0.018), and SEN: 0.014 (0.009–0.019), nor in lactulose, mannitol, or creatinine recovery. No significant differences were observed in any parameter for the regressed versus non‐regressed ASD groups. Results were consistent with previously published normal ranges. Eleven children (9/103 = 8.7% ASD and 2/30 = 6.7% SEN) had L/M recovery ratio > 0.03 (the accepted normal range cut‐off), of whom two (one ASD and one SEN) had more definitely pathological L/M recovery ratios > 0.04. Conclusion There is no statistically significant group difference in small intestine permeability in a population cohort‐derived group of children with ASD compared with a control group with SEN. Of the two children (one ASD and one SEN) with an L/M recovery ratio of > 0.04, one had undiagnosed asymptomatic celiac disease (ASD) and the other (SEN) past extensive surgery for gastroschisis. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    December 12, 2013   doi: 10.1002/aur.1350   open full text
  • Mice Exposed to Diagnostic Ultrasound In Utero Are Less Social and More Active in Social Situations Relative to Controls.
    Abbi M. McClintic, Bryan H. King, Sara J. Webb, Pierre D. Mourad.
    Autism Research. November 18, 2013
    Clinical use of diagnostic ultrasound imaging during pregnancy has a long history of safety and diagnostic utility, as supported by numerous human case reports and epidemiological studies. However, there exist in vivo studies linking large but clinically relevant doses of ultrasound applied to mouse fetuses in utero to altered learning, memory, and neuroanatomy of those mice. Also, there exists a well‐documented significant increase in the likelihood of non‐right‐handedness in boys exposed to diagnostic ultrasound in utero, potentially relevant given the increased prevalence of autism in males, and reports of excess non‐right‐handedness in this population. Motivated by these observations, we applied 30 minutes of diagnostic ultrasound to pregnant mice at embryonic day 14.5 and assayed the social behavior of their male pups 3 weeks after their birth. The ultrasound‐exposed pups were significantly (P < 0.01) less interested in social interaction than sham‐exposed pups in a three‐chamber sociability test. In addition, they demonstrated significantly (P < 0.05) more activity relative to the sham‐exposed pups, but only in the presence of an unfamiliar mouse. These results suggest that fetal exposure to diagnostic ultrasound applied in utero can alter typical social behaviors in young mice that may be relevant for autism. There exist meaningful differences between the exposure of diagnostic ultrasound to mice versus humans that require further exploration before this work can usefully inform clinical practice. Future work should address these differences as well as clarify the extent, mechanisms, and functional effects of diagnostic ultrasound's interaction with the developing brain. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    November 18, 2013   doi: 10.1002/aur.1349   open full text
  • Impaired Comprehension of Alternating Syntactic Constructions in Autism.
    Melissa D. Stockbridge, Francesca G. E. Happé, Sarah J. White.
    Autism Research. November 13, 2013
    Individuals on the higher‐functioning end of the autism spectrum have significant impairments in communication. Language delay can occur, particularly in syntactic or structural linguistic knowledge. However, classically observed semantic deficits generally overshadow these structural deficits. This research examined the potential effects on comprehension of dative expressions that exhibited syntactic alternation versus those that were restricted, whether in syntactic construction or through marked semantic differences in construction. Children with autism and matched neurotypical control participants were presented with a sentence battery of dative statements representing these variations in construction and were asked to display basic comprehension of the sentence meaning by identifying the recipient, or indirect object, of the dative verb. Construction, restriction, and semantic differentiation variables were analyzed for potential effects on the rate of accurate comprehension. Both groups performed with greater accuracy when dative expressions used a prepositional phrase than when the dative action was expressed in the syntax. The autism group performed more poorly when the dative expression could syntactically alternate than when it was restricted. These effects improve our knowledge of how children with autism understand alternating grammatical constructions. Autism Res 2013, ●●: ●●●–●●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    November 13, 2013   doi: 10.1002/aur.1348   open full text
  • Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism.
    Luciana Lucchina, Amaicha Mara Depino.
    Autism Research. October 03, 2013
    Increasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneously with 600 mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism. Here, we show that these adult animals present signs of chronic glial activation in the hippocampus and the cerebellum. Moreover, when they are challenged with a peripheral inflammatory stimulus (intraperitoneal lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory response. Two hours after LPS injection, VPA600 animals secrete more corticosterone to the blood than control mice, and show an increase in the levels of expression of proinflammatory cytokines in the spleen. After LPS challenge, VPA600 mice also show signs of increased neuroinflammation compared with control mice: they have more microglial cells in the hippocampus, and they show higher levels of proinflammatory cytokines in the cerebellum. Our results provide evidence of basal neuroinflammation and an altered inflammatory response in the VPA model of autism. We propose that this model can be used to evaluate the contribution of inflammatory reactivity to autism‐related behaviors. These studies will contribute to elucidate the role of the inflammatory alterations observed in ASD individuals. Autism Res 2013, 7: 273–289. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    October 03, 2013   doi: 10.1002/aur.1338   open full text
  • Parental Broader Autism Subphenotypes in ASD Affected Families: Relationship to Gender, Child's Symptoms, SSRI Treatment, and Platelet Serotonin.
    Tal Levin‐Decanini, Nell Maltman, Sunday M. Francis, Steve Guter, George M. Anderson, Edwin H. Cook, Suma Jacob.
    Autism Research. August 16, 2013
    Relationships between parental broader autism phenotype (BAP) scores, gender, selective serotonin reuptake inhibitor (SSRI) treatment, serotonin (5HT) levels, and the child's symptoms were investigated in a family study of autism spectrum disorder (ASD). The Broader Autism Phenotype Questionnaire (BAPQ) was used to measure the BAP of 275 parents. Fathers not taking SSRIs (F‐SSRI; n = 115) scored significantly higher on BAP Total and Aloof subscales compared to mothers not receiving treatment (M‐SSRI; n = 136.) However, mothers taking SSRIs (M + SSRI; n = 19) scored higher than those not taking medication on BAP Total and Rigid subscales, and they were more likely to be BAPQ Total, Aloof, and Rigid positive. Significant correlations were noted between proband autism symptoms and parental BAPQ scores such that Total, Aloof, and Rigid subscale scores of F‐SSRI correlated with proband restricted repetitive behavior (RRB) measures on the ADOS, CRI, and RBS‐R. However, only the Aloof subscale score of M + SSRI correlated with proband RRB on the ADOS. The correlation between the BAPQ scores of mothers taking SSRIs and child scores, as well as the increase in BAPQ scores of this group of mothers, requires careful interpretation and further study because correlations would not withstand multiple corrections. As expected by previous research, significant parent–child correlations were observed for 5HT levels. However, 5HT levels were not correlated with behavioral measures. Study results suggest that the expression of the BAP varies not only across parental gender, but also across individuals using psychotropic medication and those who do not. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    August 16, 2013   doi: 10.1002/aur.1322   open full text
  • Autistic Traits Modulate Mimicry of Social but not Nonsocial Rewards.
    Anthony Haffey, Clare Press, Garret O'Connell, Bhismadev Chakrabarti.
    Autism Research. August 12, 2013
    Autism Spectrum Conditions (ASC) are associated with diminished responsiveness to social stimuli, and especially to social rewards such as smiles. Atypical responsiveness to social rewards, which reinforce socially appropriate behavior in children, can potentially lead to a cascade of deficits in social behavior. Individuals with ASC often show diminished spontaneous mimicry of social stimuli in a natural setting. In the general population, mimicry is modulated both by the reward value and the sociality of the stimulus (i.e., whether the stimulus is perceived to belong to a conspecific or an inanimate object). Since empathy and autistic traits are distributed continuously in the general population, this study aimed to test if and how these traits modulated automatic mimicry of rewarded social and nonsocial stimuli. High and low rewards were associated with human and robot hands using a conditioned learning paradigm. Thirty‐six participants from the general population then completed a mimicry task involving performing a prespecified hand movement which was either compatible or incompatible with a hand movement presented to the participant. High autistic traits (measured using the Autism Spectrum Quotient, AQ) predicted lesser mimicry of high‐reward than low‐reward conditioned human hands, whereas trait empathy showed an opposite pattern of correlations. No such relations were observed for high‐reward vs. low‐reward conditioned robot hands. These results demonstrate how autistic traits and empathy modulate the effects of reward on mimicry of social compared to nonsocial stimuli. This evidence suggests a potential role for the reward system in underlying the atypical social behavior in individuals with ASC, who constitute the extreme end of the spectrum of autistic traits. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    August 12, 2013   doi: 10.1002/aur.1323   open full text
  • More Is Less: Pitch Discrimination and Language Delays in Children with Optimal Outcomes from Autism.
    Inge‐Marie Eigsti, Deborah A. Fein.
    Autism Research. August 08, 2013
    The autism spectrum disorders (ASD) are neurodevelopmental disorders diagnosed behaviorally but associated with differences in brain development. Individuals with ASD exhibit superior auditory perceptual skills, which may correlate with ASD symptomatology, particularly language skills. We describe findings from individuals diagnosed with ASD before age five, who now have no symptoms (e.g., having optimal outcomes). Unlike an ASD group, which shows heightened pitch discrimination, the Optimal Outcome group's abilities do not differ from those of typically developing controls. Furthermore, pitch discrimination is associated with both current autism symptomatology and early‐language milestones. Findings illuminate processes associated with resolution of autism. We also discuss a specific mechanism by which heightened auditory discrimination leads to language delays in ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    August 08, 2013   doi: 10.1002/aur.1324   open full text
  • Recognition of Face and Non‐Face Stimuli in Autistic Spectrum Disorder.
    Leo Arkush, Adam P. R. Smith‐Collins, Chiara Fiorentini, David H. Skuse.
    Autism Research. July 25, 2013
    The ability to remember faces is critical for the development of social competence. From childhood to adulthood, we acquire a high level of expertise in the recognition of facial images, and neural processes become dedicated to sustaining competence. Many people with autism spectrum disorder (ASD) have poor face recognition memory; changes in hairstyle or other non‐facial features in an otherwise familiar person affect their recollection skills. The observation implies that they may not use the configuration of the inner face to achieve memory competence, but bolster performance in other ways. We aimed to test this hypothesis by comparing the performance of a group of high‐functioning unmedicated adolescents with ASD and a matched control group on a “surprise” face recognition memory task. We compared their memory for unfamiliar faces with their memory for images of houses. To evaluate the role that is played by peripheral cues in assisting recognition memory, we cropped both sets of pictures, retaining only the most salient central features. ASD adolescents had poorer recognition memory for faces than typical controls, but their recognition memory for houses was unimpaired. Cropping images of faces did not disproportionately influence their recall accuracy, relative to controls. House recognition skills (cropped and uncropped) were similar in both groups. In the ASD group only, performance on both sets of task was closely correlated, implying that memory for faces and other complex pictorial stimuli is achieved by domain‐general (non‐dedicated) cognitive mechanisms. Adolescents with ASD apparently do not use domain‐specialized processing of inner facial cues to support face recognition memory. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 25, 2013   doi: 10.1002/aur.1318   open full text
  • Reward‐Based Decision Making and Electrodermal Responding by Young Children with Autism Spectrum Disorders during a Gambling Task.
    Susan Faja, Michael Murias, Theodore P. Beauchaine, Geraldine Dawson.
    Autism Research. July 24, 2013
    In this study, we explore reward‐based decision making and electrodermal responding (EDR) among children with autism spectrum disorder (ASD) during a children's gambling task. In addition, we examine whether individual behavioral and EDR responses predict social communication, repetitive symptoms, parent reports of executive function, and behavioral challenges. The ability to form advantageous strategies for long‐term gain is of interest for children with ASD, who exhibit both difficulty with executive function and atypical responses to reward. Twenty‐one children ages 6–7 years with ASD and no intellectual disability, and 21 age‐ and IQ‐matched typically developing children participated. Both groups exhibited a similar pattern of gambling selections, but children with ASD showed less knowledge of the reward contingencies of the decks after playing. In addition, although EDR was similar between groups in anticipation of selections, children with ASD exhibited greater EDR during feedback about rewards as the task progressed. Children with ASD who exhibited the greatest increases in EDR were more likely to exhibit repetitive symptoms, particularly rituals and the need for sameness, as well as internalizing behaviors and reduced executive function in other settings. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 24, 2013   doi: 10.1002/aur.1307   open full text
  • Reduced Serotonin Receptor Subtypes in a Limbic and a Neocortical Region in Autism.
    Adrian Oblak, Terrell T. Gibbs, Gene J. Blatt.
    Autism Research. July 24, 2013
    Autism is a behaviorally defined, neurological disorder with symptom onset before the age of 3. Abnormalities in social‐emotional behaviors are a core deficit in autism, and are characterized by impaired reciprocal–social interaction, lack of facial expressions, and the inability to recognize familiar faces. The posterior cingulate cortex (PCC) and fusiform gyrus (FG) are two regions within an extensive limbic‐cortical network that contribute to social‐emotional behaviors. Evidence indicates that changes in brains of individuals with autism begin prenatally. Serotonin (5‐HT) is one of the earliest expressed neurotransmitters, and plays an important role in synaptogenesis, neurite outgrowth, and neuronal migration. Abnormalities in 5‐HT systems have been implicated in several psychiatric disorders, including autism, as evidenced by immunology, imaging, genetics, pharmacotherapy, and neuropathology. Although information is known regarding peripheral 5‐HT in autism, there is emerging evidence that 5‐HT systems in the central nervous system, including various 5‐HT receptor subtypes and transporters, are affected in autism. The present study demonstrated significant reductions in 5‐HT1A receptor‐binding density in superficial and deep layers of the PCC and FG, and in the density of 5‐HT2A receptors in superficial layers of the PCC and FG. A significant reduction in the density of serotonin transporters (5‐HTT) was also found in the deep layers of the FG, but normal levels were demonstrated in both layers of the PCC and superficial layers of the FG. This study provides potential substrates for decreased 5‐HT modulation/innervation in the autism brain, and implicate two 5‐HT receptor subtypes as potential neuromarkers for novel or existing pharmacotherapies. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 24, 2013   doi: 10.1002/aur.1317   open full text
  • Specific Neurological Phenotypes in Autism Spectrum Disorders Are Associated with Sex Representation.
    Esther Ben‐Itzchak, Shay Ben‐Shachar, Ditza A. Zachor.
    Autism Research. July 19, 2013
    Autism spectrum disorder (ASD) is a heritable disorder occurring predominantly in males. The aim of this study was to compare sex differences in the prevalence of specific neurological phenotypes commonly described in ASD. The study included 663 participants, aged 18 months to 15 years, diagnosed with ASD. Neurological and behavioral assessments were performed using standardized tests, and obtaining medical, developmental, and familial histories from the parents. Phenotypes under investigation were macro‐ and microcephaly, developmental regression, minor neurological and musculoskeletal deficits (MNMD), and seizures. Male : female ratio in the ASD group was 6.7:1. No sex differences in autism severity, cognitive ability, and adaptive functioning were noted. Mean head circumference percentile for males (50.1 ± 25.6) was significantly larger than females (43.4 ± 30.2). Micro‐ and macrocephaly were more frequent in ASD than expected (5.9%; 18.1%, respectively). Microcephaly in females (15.1%) was significantly more prevalent than in males (4.5%). The prevalence of macrocephaly in both sexes did not differ significantly. Regression was noted in 30.2% of the females with ASD, significantly higher than in males (18.9%). MNMD was documented in 73.8% of the females, significantly higher than in males (57.1%). M:F ratio decreased in a group with two or more phenotypes (3.6:1), while male predominance was more significant in the group without phenotypes (13.6:1). Neurological phenotypes associated with ASD are more prevalent in females than in males, resulting in more complex clinical and neurological manifestations in females. Therefore, involvement of different etiologies is suggested in ASD in females. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 19, 2013   doi: 10.1002/aur.1319   open full text
  • Evidence for Gender‐Specific Endophenotypes in High‐Functioning Autism Spectrum Disorder During Empathy.
    Karla Schneider, Christina Regenbogen, Katharina D. Pauly, Anna Gossen, Daniel A. Schneider, Lea Mevissen, Tanja M. Michel, Ruben C. Gur, Ute Habel, Frank Schneider.
    Autism Research. July 18, 2013
    Despite remarkable behavioral gender differences in patients with autism spectrum disorder (ASD), and growing evidence for a diminished male : female ratio for the putative “male disorder” ASD, aspects of gender are not addressed accordingly in ASD research. Our study aims at filling this gap by exploring empathy abilities in a group of 28 patients with high‐functioning ASD and 28 gender‐, age‐ and education‐matched non‐autistic subjects, for the first time by means of functional neuroimaging (fMRI). In an event‐related fMRI paradigm, emotional (“E”) and neutral (“N”) video clips presented actors telling self‐related short stories. After each clip, participants were asked to indicate their own emotion and its intensity as well as the emotion and intensity perceived for the actor. Behaviorally, we found significantly less empathic responses in the overall ASD group compared with non‐autistic subjects, and inadequate emotion recognition for the neutral clips in the female ASD group compared with healthy women. Neurally, increased activation of the bilateral medial frontal gyrus was found in male patients compared with female patients, a pattern which was not present in the non‐autistic group. Additionally, autistic women exhibited decreased activation of midbrain and limbic regions compared with non‐autistic women, whereas there was no significant difference within the male group. While we did not find a fundamental empathic deficit in autistic patients, our data propose different ways of processing empathy in autistic men and women, suggesting stronger impairments in cognitive aspects of empathy/theory of mind for men, and alterations of social reciprocity for women. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 18, 2013   doi: 10.1002/aur.1310   open full text
  • Repetitive Behavior and Restricted Interests in Young Children with Autism: Comparisons with Controls and Stability Over 2 Years.
    Lisa Joseph, Audrey Thurm, Cristan Farmer, Stacy Shumway.
    Autism Research. July 18, 2013
    Restricted, repetitive and stereotyped patterns of behavior, interests and activities [RRBs] are among the core symptoms of autism spectrum disorders (ASD). Previous studies have indicated that RRBs differentiate ASD from other developmental disorders and from typical development. This study examined the presentation of RRBs as reported on the Repetitive Behavior Scale‐Revised, a caregiver report, in children with ASD [separated into autism and Pervasive Developmental Disorder‐Not Otherwise Specified groups] compared with children with nonspectrum developmental delays or typical development. We examined the role of age, cognitive functioning, sex and social communication impairment as they relate to RRBs. The stability of RRBs in children with autism was also examined over the course of 2 years. Results of the study confirmed that the amount and type of RRBs differs by diagnosis. Age, cognitive functioning, sex and social‐communication impairment were not significant correlates. Among children with autism, RRBs remained stable over time. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 18, 2013   doi: 10.1002/aur.1316   open full text
  • Altered Structure–Function Relations of Semantic Processing in Youths with High‐Functioning Autism: A Combined Diffusion and Functional MRI Study.
    Yu‐Chun Lo, Tai‐Li Chou, Li‐Ying Fan, Susan Shur‐Fen Gau, Yen‐Nan Chiu, Wen‐Yih Isaac Tseng.
    Autism Research. July 12, 2013
    Deficits in language and communication are among the core symptoms of autism, a common neurodevelopmental disorder with long‐term impairment. Despite the striking nature of the autistic language impairment, knowledge about its corresponding alterations in the brain is still evolving. We hypothesized that the dual stream language network is altered in autism, and that this alteration could be revealed by changes in the relationships between microstructural integrity and functional activation. The study recruited 20 right‐handed male youths with autism and 20 carefully matched individually, typically developing (TD) youths. Microstructural integrity of the left dorsal and left ventral pathways responsible for language processing and the functional activation of the connected brain regions were investigated by using diffusion spectrum imaging and functional magnetic resonance imaging of a semantic task, respectively. Youths with autism had significantly poorer language function, and lower functional activation in left dorsal and left ventral regions of the language network, compared with TD youths. The TD group showed a significant correlation of the functional activation of the left dorsal region with microstructural integrity of the left ventral pathway, whereas the autism group showed a significant correlation of the functional activation of the left ventral region with microstructural integrity of the left dorsal pathway, and moreover verbal comprehension index was correlated with microstructural integrity of the left ventral pathway. These altered structure–function relationships in autism suggest possible involvement of the dual pathways in supporting deficient semantic processing. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 12, 2013   doi: 10.1002/aur.1315   open full text
  • Processing Slow and Fast Motion in Children With Autism Spectrum Conditions.
    Catherine Manning, Tony Charman, Elizabeth Pellicano.
    Autism Research. July 11, 2013
    Consistent with the dorsal stream hypothesis, difficulties processing dynamic information have previously been reported in individuals with autism spectrum conditions (ASC). However, no research has systematically compared motion processing abilities for slow and fast speeds. Here, we measured speed discrimination thresholds and motion coherence thresholds in slow (1.5 deg/sec) and fast (6 deg/sec) speed conditions in children with an ASC aged 7 to 14 years, and age‐ and ability‐matched typically developing children. Unexpectedly, children with ASC were as sensitive as typically developing children to differences in speed at both slow and fast reference speeds. Yet, elevated motion coherence thresholds were found in children with ASC, but in the slow stimulus speed condition only. Rather than having pervasive difficulties in motion processing, as predicted by the dorsal stream hypothesis, these results suggest that children with ASC have a selective difficulty in extracting coherent motion information specifically at slow speeds. Understanding the effects of stimulus parameters such as stimulus speed will be important for resolving discrepancies between previous studies examining motion coherence thresholds in ASC and also for refining theoretical models of altered autistic perception. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 11, 2013   doi: 10.1002/aur.1309   open full text
  • Theory of Mind in Children with Autism Spectrum Disorder: Do Siblings Matter?
    Nicole L. Matthews, Wendy A. Goldberg, Angela F. Lukowski.
    Autism Research. July 10, 2013
    Research indicates a positive relation between the sibling constellation and theory of mind (ToM) development in typically developing (TD) children. Less is known about this association in children with autism spectrum disorder (ASD). The current study examined the association among the presence and number of siblings, birth order, and false belief (FB) understanding in children with ASD and a TD comparison group. Two FB tasks (change of contents and change of location) and the Peabody Picture Vocabulary Test were administered to 57 children with ASD and 28 TD children during a home visit. One parent of each child reported on demographics and the sibling constellation. Separate hierarchical regressions controlled for age, receptive language ability, and scores on the Social Communication Questionnaire. In children with ASD, no association was observed between presence or number of siblings and ToM. However, the presence of older (but not younger) siblings was found to be positively associated with ToM. Children with ASD who had at least one older sibling performed similarly to the TD group, whereas children with ASD who had no older siblings performed significantly worse than the TD group. These findings indicate an advantage for FB performance in children with ASD who have an older sibling. They may bear on decisions to include older siblings or peers in intervention programs and may also contribute to a more complete understanding of the origins of individual differences in ToM ability in children with ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 10, 2013   doi: 10.1002/aur.1308   open full text
  • Reputation Management: Evidence for Ability But Reduced Propensity in Autism.
    Eilidh Cage, Elizabeth Pellicano, Punit Shah, Geoffrey Bird.
    Autism Research. July 08, 2013
    Previous research has reported that autistic adults do not manage their reputation, purportedly due to problems with theory of mind [Izuma, Matsumoto, Camerer, & Adolphs]. The current study aimed to test alternative explanations for this apparent lack of reputation management. Twenty typical and 19 autistic adults donated to charity and to a person, both when alone and when observed. In an additional manipulation, for half of the participants, the observer was also the recipient of their donations, and participants were told that this observer would subsequently have the opportunity to donate to them (motivation condition). This manipulation was designed to encourage an expectation of a reciprocal “tit‐for‐tat” strategy in the participant, which may motivate participants to change their behavior to receive more donations. The remaining participants were told that the person watching was just observing the procedure (no motivation condition). Our results replicated Izuma et al.'s finding that autistic adults did not donate more to charity when observed. Yet, in the motivation condition, both typical and autistic adults donated significantly more to the observer when watched, although this effect was significantly attenuated in autistic individuals. Results indicate that, while individuals with autism may have the ability to think about reputation, a reduced expectation of reciprocal behavior from others may reduce the degree to which they engage in reputation management. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 08, 2013   doi: 10.1002/aur.1313   open full text
  • Quantification of the Stapedial Reflex Reveals Delayed Responses in Autism.
    Richard Lukose, Kevin Brown, Carol M. Barber, Randy Joseph Kulesza.
    Autism Research. July 03, 2013
    Autism is a developmental disorder characterized, in part, by sensory abnormalities. It is well established that most if not all patients with autism have problems with auditory processing, ranging from deafness to hyperacusis, and physiological testing of auditory function (i.e. auditory brain stem responses) implicates brain stem dysfunction in autism. Additionally, previous research from this lab has revealed significantly fewer auditory brain stem neurons in autistic subjects as young as 2 years of age. These observations have led us to hypothesize that objective, noninvasive measures of auditory function can be used as an early screening tool to identify neonates with an elevated risk of carrying a diagnosis of autism. Here, we provide a detailed quantitative investigation of the acoustic stapedial reflex (ASR), a three‐ or four‐neuron brain stem circuit, in young autistic subjects and normal developing controls. Indeed, we find significantly lower thresholds, responses occurring at significantly longer latency and right–left asymmetry in autistic subjects. The results from this investigation support deficits in auditory function as a cardinal feature of autism and suggest that individuals with autism can be identified by their ASR responses. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    July 03, 2013   doi: 10.1002/aur.1297   open full text
  • Effects of Environmental Enrichment on Repetitive Behaviors in the BTBR T+tf/J Mouse Model of Autism.
    Stacey Reynolds, Meagan Urruela, Darragh P. Devine.
    Autism Research. June 28, 2013
    Lower order and higher order repetitive behaviors have been documented in the BTBR T+tf/J (BTBR) mouse strain, a mouse model that exhibits all three core behavioral domains that define autism. The purpose of this study was to evaluate the effectiveness of environmental enrichment for reducing repetitive behaviors in BTBR mice. Lower order behaviors were captured by assaying the time and sequence of grooming, while higher order behaviors were measured using pattern analysis of an object exploration task from digital recordings. Baseline scores were established at 7 weeks of age, followed by 30 days of housing in either a standard or enriched cage. As expected, BTBR mice spent significantly more time grooming and had a more rigid grooming sequence than control C57BL/6J mice did at baseline. After 30 days of enrichment housing, BTBR mice demonstrated a significant reduction in time spent grooming, resulting in levels that were lower than those exhibited by BTBR mice in standard housing. However, no changes were noted in the rigidity of their grooming sequence. In contrast to previous findings, there was no difference in repetitive patterns of exploration at baseline between BTBR and C57BL/6J mice in the object exploration test. Subsequently, enrichment did not significantly alter the number of repetitive patterns at posttest. Overall, the results suggest that environmental enrichment may be beneficial for reducing the time spent engaging in lower order repetitive behaviors, but may not change the overall quality of the behaviors when they do manifest. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    June 28, 2013   doi: 10.1002/aur.1298   open full text
  • Attention Deficit Hyperactivity Disorder Symptoms in Adults with Autism Spectrum Disorders.
    Kate Johnston, Antonia Dittner, Jessica Bramham, Clodagh Murphy, Anya Knight, Ailsa Russell.
    Autism Research. June 20, 2013
    Features of attention deficit hyperactivity disorder (ADHD) and impairments on neuropsychological, tests of attention have been documented in children with autism spectrum disorders (ASDs). To date, there has been a lack of research comparing attention in adults with ASD and adults with ADHD. In study 1, 31 adults with ASD and average intellectual function completed self‐report measures of ADHD symptoms. These were compared with self‐report measures of ADHD symptoms in 38 adults with ADHD and 29 general population controls. In study 2, 28 adults with a diagnosis of ASD were compared with an age‐ and intelligence quotient‐matched sample of 28 adults with ADHD across a range of measures of attention. Study 1 showed that 36.7% of adults with ASD met Diagnostic and Statistical Manual‐IV criteria for current ADHD “caseness” (Barkley Current self‐report scores questionnaire). Those with a diagnosis of pervasive developmental disorder—not otherwise specified were most likely to describe ADHD symptoms. The ASD group differed significantly from both the ADHD and control groups on total and individual symptom self‐report scores. On neuropsychological testing, adults with ASD and ADHD showed comparable performance on tests of selective attention. Significant group differences were seen on measures of attentional switching; adults with ADHD were significantly faster and more inaccurate, and individuals with Asperger's syndrome showed a significantly slower and more accurate response style. Self‐reported rates of ADHD among adults with ASD are significantly higher than in the general adult population and may be underdiagnosed. Adults with ASD have attentional difficulties on some neuropsychological measures. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    June 20, 2013   doi: 10.1002/aur.1283   open full text
  • Social Attention in a Virtual Public Speaking Task in Higher Functioning Children With Autism.
    William Jarrold, Peter Mundy, Mary Gwaltney, Jeremy Bailenson, Naomi Hatt, Nancy McIntyre, Kwanguk Kim, Marjorie Solomon, Stephanie Novotny, Lindsay Swain.
    Autism Research. May 20, 2013
    Impairments in social attention play a major role in autism, but little is known about their role in development after preschool. In this study, a public speaking task was used to study social attention, its moderators, and its association with classroom learning in elementary and secondary students with higher functioning autism spectrum disorder (HFASD). Thirty‐seven students with HFASD and 54 age‐ and intelligence quotient (IQ)‐matched peers without symptoms of ASD were assessed in a virtual classroom public speaking paradigm. This paradigm assessed the ability to attend to nine avatar peers seated at a table, while simultaneously answering self‐referenced questions. Students with HFASD looked less frequently to avatar peers in the classroom while talking. However, social attention was moderated in the HFASD sample such that students with lower IQ, and/or more symptoms of social anxiety, and/or more attention deficit/hyperactivity disorder inattentive symptoms, displayed more atypical social attention. Group differences were more pronounced when the classroom contained social avatars versus nonsocial targets. Moreover, measures of social attention rather than nonsocial attention were significantly associated with parent report and objective measures of learning in the classroom. The data in this study support the hypothesis of the Social Attention Model of ASD that social attention disturbance remains part of the school‐aged phenotype of autism that is related to syndrome‐specific problems in social learning. More research of this kind would likely contribute to advances in the understanding of the development of the spectrum of autism and educational intervention approaches for affected school‐aged children. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    May 20, 2013   doi: 10.1002/aur.1302   open full text
  • Individual Differences in the Real‐Time Comprehension of Children with ASD.
    Courtney E. Venker, Elizabeth R. Eernisse, Jenny R. Saffran, Susan Ellis Weismer.
    Autism Research. May 20, 2013
    Many children with autism spectrum disorders (ASD) demonstrate deficits in language comprehension, but little is known about how they process spoken language as it unfolds. Real‐time lexical comprehension is associated with language and cognition in children without ASD, suggesting that this may also be the case for children with ASD. This study adopted an individual differences approach to characterizing real‐time comprehension of familiar words in a group of 34 three‐ to six‐year‐olds with ASD. The looking‐while‐listening paradigm was employed; it measures online accuracy and latency through language‐mediated eye movements and has limited task demands. On average, children demonstrated comprehension of the familiar words, but considerable variability emerged. Children with better accuracy were faster to process the familiar words. In combination, processing speed and comprehension on a standardized language assessment explained 63% of the variance in online accuracy. Online accuracy was not correlated with autism severity or maternal education, and nonverbal cognition did not explain unique variance. Notably, online accuracy at age 5½ was related to vocabulary comprehension 3 years earlier. The words typically learned earliest in life were processed most quickly. Consistent with a dimensional view of language abilities, these findings point to similarities in patterns of language acquisition in typically developing children and those with ASD. Overall, our results emphasize the value of examining individual differences in real‐time language comprehension in this population. We propose that the looking‐while‐listening paradigm is a sensitive and valuable methodological tool that can be applied across many areas of autism research. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    May 20, 2013   doi: 10.1002/aur.1304   open full text
  • Quantifying Repetitive Speech in Autism Spectrum Disorders and Language Impairment.
    Jan P. H. Santen, Richard W. Sproat, Alison Presmanes Hill.
    Autism Research. May 09, 2013
    We report on an automatic technique for quantifying two types of repetitive speech: repetitions of what the child says him/herself (self‐repeats) and of what is uttered by an interlocutor (echolalia). We apply this technique to a sample of 111 children between the ages of four and eight: 42 typically developing children (TD), 19 children with specific language impairment (SLI), 25 children with autism spectrum disorders (ASD) plus language impairment (ALI), and 25 children with ASD with normal, non‐impaired language (ALN). The results indicate robust differences in echolalia between the TD and ASD groups as a whole (ALN + ALI), and between TD and ALN children. There were no significant differences between ALI and SLI children for echolalia or self‐repetitions. The results confirm previous findings that children with ASD repeat the language of others more than other populations of children. On the other hand, self‐repetition does not appear to be significantly more frequent in ASD, nor does it matter whether the child's echolalia occurred within one (immediate) or two turns (near‐immediate) of the adult's original utterance. Furthermore, non‐significant differences between ALN and SLI, between TD and SLI, and between ALI and TD are suggestive that echolalia may not be specific to ALN or to ASD in general. One important innovation of this work is an objective fully automatic technique for assessing the amount of repetition in a transcript of a child's utterances. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    May 09, 2013   doi: 10.1002/aur.1301   open full text
  • Association between MTHFR Gene Polymorphisms and the Risk of Autism Spectrum Disorders: A Meta‐Analysis.
    Danhua Pu, Yiping Shen, Jie Wu.
    Autism Research. May 07, 2013
    Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta‐analysis. Up to December 2012, eight case‐control studies involving 1672 patients with ASD and 6760 controls were included for meta‐analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09–1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09–2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08–3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12–2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02–2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56–0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta‐analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    May 07, 2013   doi: 10.1002/aur.1300   open full text
  • The Relationship Between Attentional Bias and Anxiety in Children and Adolescents With Autism Spectrum Disorders.
    Matthew J. Hollocks, Ann Ozsivadjian, Claire E. Matthews, Patricia Howlin, Emily Simonoff.
    Autism Research. March 21, 2013
    Young people with an autism spectrum disorder (ASD) are more likely to have heightened levels of anxiety compared with their typically developing (non‐ASD) peers. The reasons for this are poorly understood, and there has been little research investigating the cognitive correlates of anxiety in individuals with ASD. Typically developing youth with anxiety disorders have frequently been found to show an attentional bias toward threatening information. In this study, we examined whether such a bias was also found in young people with ASD and anxiety symptoms. The protocol utilized two versions of the dot‐probe paradigm, the first with emotional faces and the second with emotional words. Participants comprised 38 boys with an ASD and 41 typically developing controls aged 10–16 years of age. Those with an ASD displayed higher levels of parent‐ and child‐rated anxiety (both P < 0.001) and depression (P < 0.001) compared with controls. However, there were no significant group differences in attentional bias scores and no significant relationship between anxiety and attentional bias in either the face or word tasks, for either group. Our findings suggest that, for young people with ASD, unlike non‐ASD individuals with an anxiety disorder, high levels of anxiety may not be associated with attentional bias to threat. This may indicate that anxiety in ASD has different cognitive correlates from anxiety in the typically developing population. Further conclusions, study limitations, and future directions are discussed. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 21, 2013   doi: 10.1002/aur.1285   open full text
  • The Role of Gaze Direction in Face Memory in Autism Spectrum Disorder.
    Safa R. Zaki, Shannon A. Johnson.
    Autism Research. March 19, 2013
    We tested the hypothesis that the direction of gaze of target faces may play a role in reported face recognition deficits in those with an autism spectrum disorder (ASD). In previous studies, typically developing children and adults better remembered faces in which the eyes were gazing directly at them compared with faces in which the eyes were averted. In the current study, high‐functioning children and adolescents with an ASD and age‐ and IQ‐matched typically developing controls were shown a series of pictures of faces in a study phase. These pictures were of individuals whose gaze was either directed straight ahead or whose gaze was averted to one side. We tested the memory for these study faces in a recognition task in which the faces were shown with their eyes closed. The typically developing group better remembered the direct‐gaze faces, whereas the ASD participants did not show this effect. These results imply that there may be an important link between gaze direction and face recognition abilities in ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 19, 2013   doi: 10.1002/aur.1292   open full text
  • White Matter and Visuospatial Processing in Autism: A Constrained Spherical Deconvolution Tractography Study.
    Jane McGrath, Katherine Johnson, Erik O'Hanlon, Hugh Garavan, Louise Gallagher, Alexander Leemans.
    Autism Research. March 18, 2013
    Autism spectrum disorders (ASDs) are associated with a marked disturbance of neural functional connectivity, which may arise from disrupted organization of white matter. The aim of this study was to use constrained spherical deconvolution (CSD)‐based tractography to isolate and characterize major intrahemispheric white matter tracts that are important in visuospatial processing. CSD‐based tractography avoids a number of critical confounds that are associated with diffusion tensor tractography, and to our knowledge, this is the first time that this advanced diffusion tractography method has been used in autism research. Twenty‐five participants with ASD and aged 25, intelligence quotient‐matched controls completed a high angular resolution diffusion imaging scan. The inferior fronto‐occipital fasciculus (IFOF) and arcuate fasciculus were isolated using CSD‐based tractography. Quantitative diffusion measures of white matter microstructural organization were compared between groups and associated with visuospatial processing performance. Significant alteration of white matter organization was present in the right IFOF in individuals with ASD. In addition, poorer visuospatial processing was associated in individuals with ASD with disrupted white matter in the right IFOF. Using a novel, advanced tractography method to isolate major intrahemispheric white matter tracts in autism, this research has demonstrated that there are significant alterations in the microstructural organization of white matter in the right IFOF in ASD. This alteration was associated with poorer visuospatial processing performance in the ASD group. This study provides an insight into structural brain abnormalities that may influence atypical visuospatial processing in autism. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 18, 2013   doi: 10.1002/aur.1290   open full text
  • Serotonin Hypothesis of Autism: Implications for Selective Serotonin Reuptake Inhibitor Use during Pregnancy.
    Rebecca A. Harrington, Li‐Ching Lee, Rosa M. Crum, Andrew W. Zimmerman, Irva Hertz‐Picciotto.
    Autism Research. March 14, 2013
    Serotonin, a neurotransmitter found throughout the brain and body, has long been of interest in autism. Repeated findings of elevated platelet serotonin levels in approximately one third of children with autism has led some to believe that dysfunctional serotonin signaling may be a causal mechanism for the disorder. Because serotonin is critical to fetal brain development, concerns have arisen regarding prenatal exposure to substances that manipulate serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs). This review examines evidence regarding the serotonin system and autism spectrum disorders (ASD), as well as what the literature has reported thus far on developmental effects of prenatal exposure to SSRIs. Possible mechanisms by which SSRIs could affect the fetus during pregnancy and clinical implications are also discussed. Though the majority of studies conducted in infants and children suggest prenatal exposure to SSRIs does not affect neurodevelopment, interpretation must be tempered given small sample sizes. The only published study that focused on prenatal SSRI exposure and ASD found an increased risk with exposure to SSRIs, especially during the first trimester. Obstacles that will be faced in future research are isolating medication effects from maternal depression and, given the infrequent occurrence of exposure and outcome, obtaining an adequate sample size. Whether serotonin is an etiologic factor in ASD, and what it points to as a marker for subgrouping, remains unclear. Understanding how the development of ASD might be affected by prenatal factors that influence serotonin levels, such as SSRIs, could identify modifiable targets for prevention. Autism Res 2013, 6: 149–168. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 14, 2013   doi: 10.1002/aur.1288   open full text
  • The Interstitial Duplication 15q11.2‐q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature.
    Nora Urraca, Julie Cleary, Victoria Brewer, Eniko K. Pivnick, Kathryn McVicar, Ronald L. Thibert, N. Carolyn Schanen, Carmen Esmer, Dustin Lamport, Lawrence T. Reiter.
    Autism Research. March 14, 2013
    Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism‐associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2‐q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 14, 2013   doi: 10.1002/aur.1284   open full text
  • Testing the Predictive Power of Cognitive Atypicalities in Autistic Children: Evidence from a 3‐Year Follow‐Up Study.
    Elizabeth Pellicano.
    Autism Research. March 14, 2013
    This follow‐up study investigated the predictive power of early cognitive atypicalities. Specifically, it examined whether early individual differences in specific cognitive skills, including theory of mind, executive function, and central coherence, could uniquely account for variation in autistic children's behaviors—social communication, repetitive behaviors, and interests and insistence on sameness—at follow‐up. Thirty‐seven cognitively able children with an autism spectrum condition were assessed on tests tapping verbal and nonverbal ability, theory of mind (false‐belief prediction), executive function (planning ability, cognitive flexibility, and inhibitory control), and central coherence (local processing) at intake and their behavioral functioning (social communication, repetitive behaviors and interests, insistence on sameness) 3 years later. Individual differences in early executive but not theory of mind skills predicted variation in children's social communication. Individual differences in children's early executive function also predicted the degree of repetitive behaviors and interests at follow‐up. There were no predictive relationships between early central coherence and children's insistence on sameness. These findings challenge the notion that distinct cognitive atypicalities map on to specific behavioral features of autism. Instead, early variation in executive function plays a key role in helping to shape autistic children's emerging behaviors, including their social communication and repetitive behaviors and interests. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 14, 2013   doi: 10.1002/aur.1286   open full text
  • Fear‐Potentiated Startle Response Is Unrelated to Social or Emotional Functioning in Adolescents With Autism Spectrum Disorders.
    Lindsey Sterling, Jeffrey Munson, Annette Estes, Michael Murias, Sara Jane Webb, Bryan King, Geraldine Dawson.
    Autism Research. March 14, 2013
    It has been suggested that atypical amygdala function contributes to the social impairments characteristic of autism spectrum disorders (ASDs). Previous research has demonstrated that adolescents and adults with ASD generate normal response during a fear‐potentiated startle paradigm, suggesting this aspect of amygdala function is intact and may not account for the social dysfunction associated with the condition. The amygdala also plays a crucial role in the expression of anxiety and may contribute to high rates of reported anxiety in individuals with ASD. The present study partially replicates prior work by examining the fear‐potentiated startle response in adolescents with ASD, and extends this to investigate the relationship between startle response and anxiety. Eyeblink magnitude and latency (electromyographic activity; EMG) were collected from 20 adolescents with ASD and 19 typically developing (TD) age‐matched adolescents during a fear‐potentiated startle paradigm. Parent‐report and self‐report of anxiety and additional psychiatric symptoms were collected. Parental reports indicated higher rates of associated psychopathology in adolescents with ASD compared with TD adolescents. Consistent with previous results, both groups showed normal potentiated startle response, and no group differences in EMG were found. Symptoms of anxiety and level of social impairment were unrelated to startle response. These findings held for all levels of anxiety, suggesting that within the context of the fear‐potentiated startle paradigm, amygdala response is not associated with degree of atypical social or emotional functioning in ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 14, 2013   doi: 10.1002/aur.1289   open full text
  • Brain Function Differences in Language Processing in Children and Adults with Autism.
    Diane L. Williams, Vladimir L. Cherkassky, Robert A. Mason, Timothy A. Keller, Nancy J. Minshew, Marcel Adam Just.
    Autism Research. March 14, 2013
    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language‐processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 14, 2013   doi: 10.1002/aur.1291   open full text
  • Prenatal and Early‐Life Exposure to High‐Level Diesel Exhaust Particles Leads to Increased Locomotor Activity and Repetitive Behaviors in Mice.
    Keerthi Thirtamara Rajamani, Shannon Doherty‐Lyons, Crystal Bolden, Daniel Willis, Carol Hoffman, Judith Zelikoff, Lung‐Chi Chen, Howard Gu.
    Autism Research. March 11, 2013
    Abundant evidence indicates that both genetic and environmental factors contribute to the etiology of autism spectrum disorders (ASDs). However, limited knowledge is available concerning these contributing factors. An epidemiology study reported a link between increased incidence of autism and living closely to major highways, suggesting a possible role for pollutants from highway traffic. We investigated whether maternal exposure to diesel exhaust particles (DEP) negatively affects fetal development leading to autism‐like phenotype in mice. Female mice and their offspring were exposed to DEP during pregnancy and nursing. Adult male offspring were then tested for behaviors reflecting the typical symptoms of ASD patients. Compared to control mice, DEP‐exposed offspring exhibited higher locomotor activity, elevated levels of self‐grooming in the presence of an unfamiliar mouse, and increased rearing behaviors, which may be relevant to the restricted and repetitive behaviors seen in ASD patients. However, the DEP‐exposed mice did not exhibit deficits in social interactions or social communication which are the key features of ASD. These results suggest that early life exposure to DEP could have an impact on mouse development leading to observable changes in animal behaviors. Further studies are needed to reveal other environmental insults and genetic factors that would lead to animal models expressing key phenotypes of the autism spectrum disorders. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    March 11, 2013   doi: 10.1002/aur.1287   open full text
  • Letting a Typical Mouse Judge Whether Mouse Social Interactions Are Atypical.
    Charisma R. Shah, Carl Gunnar Forsberg, Jing‐Qiong Kang, Jeremy Veenstra‐VanderWeele.
    Autism Research. February 21, 2013
    Diagnosis of an autism spectrum disorder (ASD) requires a qualitative assessment of social aptitude: one person judging whether another person interacts in a “typical” way. We hypothesized that mice could be used to make a similar judgment if they prefer “typical” over “atypical” social interactions with mouse models relevant to ASD. We used wild‐type C57BL/6 (B6) mice as “judges” and evaluated their preference for a chamber containing a “typical” (B6 or 129S6) or an “atypical” mouse. For our atypical mouse stimuli, we chose two inbred strains with well‐documented social phenotypes (BTBR and BALB/c), as well a mutant line with abnormal social behavior and seizures (Gabrb3 +/−). Overall, we observed a stimulus by time interaction (P < 0.0001), with B6 mice preferring the typical mouse chamber during the last 10 min of the 30‐min test. For two of the individual stimulus pairings, we observed a similar chamber by time interaction (BALB/c vs. 129S6, P = 0.0007; Gabrb3 +/− vs. 129S6, P = 0.033). For the third stimulus pairing, we found a trend for preference of the typical mouse across time (BTBR vs. B6, P = 0.051). We repeated the experiments using 129S6 mice as judges and found a significant overall interaction (P = 0.034), but only one stimulus pairing reached significance on its own (BALB/c vs. 129S6, P = 0.0021). These data suggest that a characteristic pattern of exploration in B6 mice can distinguish some socially atypical animals from controls. Autism Res 2013, 6: 212–220. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    February 21, 2013   doi: 10.1002/aur.1280   open full text
  • Is There a Bidirectional Relationship Between Maternal Well‐Being and Child Behavior Problems in Autism Spectrum Disorders? Longitudinal Analysis of a Population‐Defined Sample of Young Children.
    Vasiliki Totsika, Richard P. Hastings, Eric Emerson, Gillian A. Lancaster, Damon M. Berridge, Dimitrios Vagenas.
    Autism Research. February 21, 2013
    The aim of this study was to examine whether the relationship between maternal psychological well‐being and behavior problems in children with an autism spectrum disorder (ASD) is bidirectional. Data were available at 9 months, 3 years, and 5 years old for 132 children with ASD, identified from a population‐representative sample of UK children. Three‐wave cross‐lagged models examined reciprocal effects between child behavior and maternal well‐being (psychological distress, physical health functioning, and life satisfaction). Results indicated that the relationships between maternal well‐being and child problem behaviors were not bidirectional. Specifically, findings suggested that while early behavior problems are not a risk factor for later maternal well‐being, maternal psychological distress, physical health limitations, and lower life satisfaction are risk factors for later child behavior problems. Autism Res 2013, 6: 201–211. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    February 21, 2013   doi: 10.1002/aur.1279   open full text
  • Eye Movement Difficulties in Autism Spectrum Disorder: Implications for Implicit Contextual Learning.
    Anastasia Kourkoulou, Gustav Kuhn, John M. Findlay, Susan R. Leekam.
    Autism Research. February 21, 2013
    It is widely accepted that we use contextual information to guide our gaze when searching for an object. People with autism spectrum disorder (ASD) also utilise contextual information in this way; yet, their visual search in tasks of this kind is much slower compared with people without ASD. The aim of the current study was to explore the reason for this by measuring eye movements. Eye movement analyses revealed that the slowing of visual search was not caused by making a greater number of fixations. Instead, participants in the ASD group were slower to launch their first saccade, and the duration of their fixations was longer. These results indicate that slowed search in ASD in contextual learning tasks is not due to differences in the spatial allocation of attention but due to temporal delays in the initial‐reflexive orienting of attention and subsequent‐focused attention. These results have broader implications for understanding the unusual attention profile of individuals with ASD and how their attention may be shaped by learning. Autism Res 2013, 6: 177–189. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    February 21, 2013   doi: 10.1002/aur.1274   open full text
  • Behavior and Sleep Problems in Children With a Family History of Autism.
    Amy Jo Schwichtenberg, Gregory S. Young, Ted Hutman, Ana‐Maria Iosif, Marian Sigman, Sally J. Rogers, Sally Ozonoff.
    Autism Research. February 21, 2013
    The present study explores behavioral and sleep outcomes in preschool‐age siblings of children with autism spectrum disorders (ASD). This study focuses on behavior problems that are common in children with ASD, such as emotional reactivity, anxiety, inattention, aggression, and sleep problems. Infant siblings were recruited from families with at least one older child with ASD (high‐risk group, n = 104) or families with no history of ASD (low‐risk group, n = 76). As part of a longitudinal prospective study, children completed the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule, and parents completed the Child Behavior Checklist (CBCL) and the Social Communication Questionnaire at 36 months of age. This study focuses on developmental concerns outside of ASD; therefore, only siblings who did not develop an ASD were included in analyses. Negative binomial regression analyses revealed that children in the high‐risk group were more likely to have elevated behavior problems on the CBCL Anxious/Depressed and Aggression subscales. To explore sleep problems as a correlate of these behavior problems, a second series of models was specified. For both groups of children, sleep problems were associated with elevated behavior problems in each of the areas assessed (reactivity, anxiety, somatic complaints, withdrawal, attention, and aggression). These findings support close monitoring of children with a family history of ASD for both behavioral and sleep issues. Autism Res 2013, 6: 169–176. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    February 21, 2013   doi: 10.1002/aur.1278   open full text
  • Functional Assays of Local Connectivity in the Somatosensory Cortex of Individuals with Autism.
    Mehmet Akif Coskun, Katherine A. Loveland, Deborah A. Pearson, Andrew C. Papanicolaou, Bhavin R. Sheth.
    Autism Research. February 20, 2013
    Emerging evidence for differences between individuals with autism spectrum disorder (ASD) and neurotypical (NT) individuals in somatic processing and brain response to touch suggests somatosensory cortex as a promising substrate for elucidating differences in functional brain connectivity between individuals with and without autism. Signals from adjacent digits project to neighboring locations or representations in somatosensory cortex. When a digit is stimulated, i.e. touched, its representation in cortex is directly activated; local intracortical connections indirectly activate nonprimary cortical representations corresponding to adjacent digits. The response of the nonprimary cortical representations is thus a proxy for connection strength. Local overconnectivity in autism implies that the nonprimary/primary response ratios of the ASD group will be higher than those of the NT group. D1 and D2 of the dominant hand of the participant were individually stimulated while we recorded neural responses using magnetoencephalography. The cortical representations of D1 and D2 (somatosensory‐evoked fields) were computed from the ensemble‐averaged data using (a) dipole model fits and (b) singular value decomposition. Individual adjacent/primary response ratios were measured, and group response ratio data were fitted with straight lines. Local overconnectivity in autism implies steeper ASD vs. NT group slopes. Our findings did not support local overconnectivity. Slopes were found to be significantly shallower for the ASD group than the NT group. Our findings support the idea of local underconnectivity in the somatosensory cortex of the brains of individuals with ASD. Autism Res 2013, 6: 190–200. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
    February 20, 2013   doi: 10.1002/aur.1276   open full text