Clinical characteristics of major depression that predict risk of depression in relatives

Background: Major depression (MD) is both clinically and etiologically hete rogeneous. Wt attempt to relate clinical and etiologic heterogeneity by det ermining those features of MD that reflect a high familial liability to dep ressive illness. Methods: Our sample, 3786 personally interviewed twin pairs from a populati on-based registry, contained 1765 people with a lifetime history of MD by D SM-III-R criterial of whom 639 (36.2%) had affected co-twins. We examine, u sing Cox proportional hazard models, the clinical features of MD in affecte d twins that predicted the risk for MD in the co-twin. Control variables we re zygosity, age at interview, and sex of the twin and co-twin. Results: The best-fitting, model contained 4 significant predictors: number of episodes, duration of longest episode, recurrent thoughts of death or s uicide, and level of distress or impairment. These 4 clinical features were similarly predictive of the risk for MD in the co-twins of male and female twins and predicted risk of illness more strongly in monozygotic than in d izygotic twins. Variables that did not uniquely predict risk of MD in the c otwin included age at onset and number of depressive symptoms. For number o f episodes, the best-fitting model indicated an inverted U-shaped function with greatest cotwin risk for MD with 7 to 9 lifetime episodes. Conclusions: The clinical features of MD in epidemiologic samples can be me aningfully related to the familial vulnerability to illness. Familial MD is best characterized by intermediate levels of recurrence, long duration of episodes, high levels of impairment, and recurrent thoughts of death or sui cide. These clinical features probably reflect a high genetic liability to depressive illness.