Sex-specific genetic influences on the comorbidity of alcoholism and major depression 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 adoption studies of these disorders have used cases ascertained through treatment settings, who may differ from cases in epidemiological samples. We studied 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 dependence were assessed by structured interview for both members of 3755 twin pairs from the Mid-Atlantic Twin Registry. Pair resemblance was analyzed by means of structural equation models. RESULTS: Individuals with MD were at significantly increased risk for alcohol dependence and for a combined diagnosis of alcohol abuse and/or dependence. History of MD in a twin significantly increased the risk of cotwin alcohol dependence and alcohol abuse and/or dependence among identical male pairs and for alcohol abuse and/or dependence 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. This overlap was significant only within sex, not across sexes. CONCLUSIONS: In this population-based twin sample, the familial transmission of MD and alcohol dependence was largely disorder specific. Comorbidity appears to be due to sex-specific genetic and environmental risk factors. The factors underlying depression in women do not appear to arise from the same factors underlying alcoholism in men.