Depression is a common co-morbidity in patients with multiple sclerosis (MS). While somatic symptoms of MS correlate with depression levels, it is unclear whether the clinical presentation of MS-associated depression differs from patients with "idiopathic" major depressive disorder (MDD).

To compare the clinical phenotype of depression among MS and idiopathic MDD patients.

Mean relative contribution of individual Beck Depression Inventory-II (BDI-II) items was evaluated among n = 139 patients with relapsing-remitting MS and n = 85 MDD patients without somatic illness. Next, comparisons were repeated in n = 38 MS with clinically relevant depressive symptoms (BDI-II > 19) and n = 38 MDD patients matched for sex, age, and depression severity. Finally, the underlying construct of depression was compared across groups using confirmatory factor analysis (CFA).

Comparisons on a whole-group level produced the expected differences along somatic/non-somatic symptoms. However, when appropriately controlling for depression severity, age, and sex, only four items contributed differentially to BDI-II total scores in MS versus MDD. CFA suggested that the underlying depression construct is essentially identical in both groups.

The clinical phenotype of "idiopathic" MDD and MS-associated depression appears similar when adequately examined. The relevance of these findings for psychotherapeutic approaches for MS-associated depression should be explored in future studies.