The diagnostic validity of melancholic major depression in a population-based sample of female twins

Background: Although the diagnosis of melancholia is among the oldest in psychiatry, the validity of the melancholic subtype of major depression (MD) is still debated. If melancholia is a valid subtype of depression, is it quantitatively more severe than or qualitatively distinct from nonmelancholic depression? Methods: The lifetime history of MD and melancholia, defined by DSM-IV criteria, was assessed at interview in 1902 female twins selected from a population-based register. Patterns of comorbidity and the relationship between melancholia and risk for MD in the co-twin were assessed by logistic regression and Cox proportional hazards models, respectively. Results: In those with a lifetime history of MD, melancholia was associated with the following: (1) increased comorbidity with anxiety disorders and nicotine dependence but not alcohol dependence or bulimia; (2) greater number of episodes, more impairment, and help seeking; (3) lower levels of neuroticism; and (4) an increased risk of MD in cotwins-greater in monozygotic than in dizygotic pairs. Within hin pairs concordant for MD, no resemblance was found for melancholia. A multiple threshold model in which melancholic MD represented a quantitatively more severe form of depressive illness fitted the data. Conclusions: Melancholia, defined by DSM-IV criteria, is a valid subtype of MD and identifies a subset of affected individuals with distinct clinical features and a particularly high familial liability to depressive illness. However, from a familial perspective, the differences between melancholic and nonmelancholic MD are quantitative, not qualitative. ie, melancholic MD is more severe than, but is not etiologically distinct from, nonmelancholic MD.