GENETIC SEGREGATION ANALYSIS OF EARLY-ONSET RECURRENT UNIPOLAR DEPRESSION

Major depression is a relatively common psychiatric disorder that can be quite debilitating. Family, twin, and adoption studies indicate tha t unipolar depression has both genetic and environmental components. E arly age at onset and recurrent episodes in the proband each increase the familiality of the illness. To investigate the potential genetic u nderpinnings of the disease, we have performed a complex segregation a nalysis on 832 individuals from 50 multigenerational families ascertai ned through a proband with early-onset recurrent unipolar major depres sion. The analysis was conducted by use of regressive models, to test a variety of hypotheses to explain the familial aggregation of recurre nt unipolar depression. Analyses were conducted under two alternative definitions of affection status for the relatives of probands: (1) ''n arrow,'' in which relatives were assumed to be affected only if they w ere diagnosed with recurrent unipolar depression; and (2) ''broad,'' i n which relatives were assumed to be affected if diagnosed with any ma jor affective illness. Under the narrow-definition assumption, the mod el that best explains these family data is a transmitted (although non -Mendelian) recessive major effect with significant residual parental effects on affection status. Under the broad-definition assumption, th e best-fitting model is a Mendelian codominant major locus with signif icant residual parental and spousal effects.