Background. Numerous studies have documented high rates of co-morbidity between major depressive disorder (MDD) and the anxiety disorders (ANX). However, the reason for this is unclear. Family studies provide one potentially useful approach for addressing this issue.

Method. We explored six explanations of the co-morbidity between MDD and ANX using a family study of a large community sample of young adults and their first-degree relatives. Participants included 112 probands with a lifetime history of both MDD and one or more ANX, 290 probands with a history of MDD but no ANX, 43 probands with a history of one or more ANX but no MDD, 352 probands with no lifetime history of either MDD or ANX, and the probands' 2608 first-degree relatives. Probands were assessed using semi-structured diagnostic interviews on two occasions in adolescence and a third time at age 24. Diagnostic data on relatives were collected using both direct and family history interviews.

Results. Compared with controls, MDD aggregated in the families of probands with MDD, whether or not they had co-morbid ANX; ANX aggregated in the families of probands with ANX, regardless of whether they had co-morbid MDD; and co-morbid MDD/ANX aggregated only in the families of probands with both MDD and ANX. The relatives of probands with ANX alone had a significantly higher rate of ANX than the relatives of probands with MDD alone, although none of the other comparisons between the depressed and anxious groups were significant.

Conclusions. This pattern of findings is largely, although not completely, consistent with the view that MDD and ANX are transmitted independently within families, and suggests that the co-morbidity between MDD and ANX is caused by non-familial aetiological factors.