Partially distinct combinations of psychological, metabolic and inflammatory risk factors are prospectively associated with the onset of the subtypes of Major Depressive Disorder in midlife.

Given the well known heterogeneity of Major Depressive Disorder (MDD), dividing this complex disorder into subtypes is likely to be a more promising approach to identify its determinants than to study it as a whole. In a prospective population-based cohort study (CoLaus|PsyCoLaus) with 5.5 years of follow-up, 1524 participants without MDD at baseline, aged 35-66 years (mean age 51.4 years, 43.4% females), participated in the physical and psychiatric baseline and the psychiatric follow-up evaluations. The incidence of both atypical and melancholic MDD during the follow-up period were predicted by female sex, a lifetime history of minor depressive disorders and higher neuroticism scores. Higher baseline body mass index was associated with the onset of atypical MDD, whereas the absence of hypertension and younger age were associated with the development of melancholic MDD. Unspecified MDD was predicted by younger age, low concentrations of tumor necrosis factor-α and elevated life-event impact scores. The age range of our cohort restricts the identification of risk factors to MDD with onset in midlife and the recruitment in an urban area limits the generalizability of the findings. Our data suggest that MDD subtypes are predicted by partially distinct combinations of baseline characteristics suggesting that these subtypes not only differ in their clinical manifestations but also in factors that contribute to their development. Subjects with minor depressive episodes, especially in combination with particular personality features, deserve close clinical attention to prevent the subsequent onset of atypical and melancholic major depression