Early onset (under age 30 years) and panic disorder as markers for etiologic homogeneity in major depression

Early onset of major depression (age, less than 30 years) in probands confers high risk to relatives, whereas late-onset depression (age, greater than 40 years) involves no elevation of risk over population rates. Analyses of data from families of probands with early onset from the Yale Family Study (47 three generation and 17 two generation) favored a major gene effect over polygenic inheritance. However, no genetic model was supported unambiguously. The increase in prevalence of depression over the past several decades complicates the genetic interpretation of results. Restriction of analyses to older (age, greater than 18 years) age cohorts appeared to simplify the pattern of transmission, but a consequent reduction of sample size provided only limited power for tests of competing genetic hypotheses. In a subgroup of 28 families in which the proband had both depression and panic disorder, a major gene mode of inheritance was not supported.