Age-at-onset and comorbidity may separate depressive disorder subtypes along a descending gradient of bipolar propensity.

Depressive illnesses with subthreshold bipolar features are still misdiagnosed as unipolar. The goal of this study was to identify depressive disorder subtypes at risk for bipolarity. Four hundred ninety three major depressive patients were submitted to a cluster analysis on the basis of affective illness history and symptoms of the current episode. Seven clusters were identified which were regrouped into three age-at-onset subgroups; subgroups were further differentiated into subtypes according to predominant comorbidities. The latter were found to precede the occurrence of the related depressive disorder subtypes, decrease their age-at-onset, and increase their risk of belonging to the bipolar spectrum: the earlier the comorbidity, the higher the bipolar propensity was. This is likely to have implications for the diagnosis, natural history, as well as prophylaxis of bipolar disorders.