Sex-specific genetic influences on the comorbidity of alcoholism and majordepression in a population-based sample of US twins

Background: Alcoholism and depression frequently co-occur, but the origins of this comorbidity remain uncertain. Most previous family, twin, and adopt ion studies of these disorders have used cases ascertained through treatmen t settings, who may differ from cases in epidemiological samples. We studie d the importance of genetic influences on risk for lifetime comorbidity of major depression and alcoholism by means of a population-based twin sample. Methods: Lifetime major depression (MD), alcohol abuse, and alcohol depende nce were assessed by structured interview for both members of 3755 twin pai rs from the Mid-Atlantic Twin Registry. Pair resemblance was analyzed by me ans of structural equation models. Results: Individuals with MD were at sig nificantly increased risk for alcohol dependence and for a combined diagnos is of alcohol abuse and/or dependence. History of MD in a twin significantl y increased the risk of cotwin alcohol dependence and alcohol abuse and/or dependence among identical male pairs and for alcohol abuse and/or dependen ce in identical female pairs, but not among male or female fraternal pairs. Results of structural modeling indicate that comorbidity occurs because the genetic and specific environmental sources of liability to MD overlap with those underlying alcohol dependence and alcohol abuse and/or dependence. T his overlap was significant only within sex, not across sexes. Conclusions: In this population-based twin sample, the familial transmissio n of MD and alcohol dependence was largely disorder specific. Comorbidity a ppears to be due to sex-specific genetic and environmental risk factors. Th e factors underlying depression in women do not appear to arise from the sa me factors underlying alcoholism in men.