Understanding the clinical heterogeneity of major depression using family data.

For major depression, putative subgroups have been defined by age at onset, clinical severity, symptom patterns, or the presence of other disorders (comorbidity), yet the high degree of overlap in clinical presentation makes it difficult to determine which combination of criteria for defining subgroups best predicts familial aggregation. In dealing with this overlap, we found that only early age at onset, or major depression with an anxiety disorder or secondary alcoholism, were independently related to increased risk of major depression in relatives. Once the effects of these proband factors had been taken into account, endogenous, delusional, melancholic, or autonomous symptom patterns, recurrent depression, history of hospitalization, and suicidal ideation or attempts in probands were not associated with increased risk of major depression in relatives.