What Is the Influence of Sex and Genetics on Alcohol and Depression Comorbidity?
ABSTRACT & COMMENTARY
Source: Prescott CA, et al. Sex-specific genetic influences on the
comorbidity of alcoholism and major depression in a population-based sample of U.S. twins. Arch Gen Psychiatry 2000;57:803-811.
Alcoholism and depression occur at levels higher than chance in clinical and epidemiological settings. The current study addresses two key limitations in the literature: 1) family studies cannot distinguish whether vulnerability is transmitted through genetic or environmental means; 2) cases in treatment settings are more severe and may be significantly different than community samples (a brief comparison follows):
Treatment Samples
• Probands with alcoholism: generally, relatives are not at increased risk for depression unless the proband has depression.
• Probands with depression: relatives have no increase in alcoholism unless probands are also alcoholic.
• Probands with both alcoholism and depression: relatives are not at increased risk for alcoholism compared to relatives of probands with alcoholism alone.
Community Samples
• Probands with alcoholism: relatives are at increased risk for depression.
• Probands with depression: relatives have increased risk for alcoholism.
• Probands with both alcoholism and depression: relatives are at increased risk for alcoholism.
Subjects were obtained from two longitudinal twin studies of psychiatric and substance-related disorders of female-female (FF) pairs (n = 2164) and male-male (MM)/male-female (MF) pairs (n = 6847). Caucasian twins were born between 1934 and 1974, had a mean age of 35, and had a mean education of 13.4 years. Structured interviews were done in accordance with Diagnostic and Statistical Manual of Mental Disorders DSM-IV. Genetic, common environmental, and specific environmental contributions to liability were determined.
Depression was more common in women and alcohol disorders were more prevalent in men. Among comorbid individuals, 61% of men reported their alcoholism preceded depression, while 68% of women said the opposite. Correlations between depression and alcoholism were modest: 0.24-0.31 among men and 0.29-0.37 for women. Individuals with depression were at significantly increased risk for alcohol dependence and for a combined diagnosis of alcohol abuse and/or dependence. History of depression in a twin significantly increased the risk of co-twin alcohol dependence and alcohol abuse and/or dependence among identical male pairs and for identical female pairs. Comorbidity occurs because the genetic and specific environmental sources of liability to depression overlap with those underlying alcohol dependence and alcohol abuse and/or dependence. This overlap was significant only within sex, not across sexes. Limitations include the sample not potentially being generalizable, to the population at-large and in addition, the classification of cases into primary and secondary alcoholism was based on timing of episodes, which may not correspond to what is etiologically primary.
COMMENT BY DONALD M. HILTY, MD
The results do not support a causal model of depression causing alcoholism or vice-versa. There are genetic and specific environmental factors that influence both disorders, and other influences specific to each disorder. The overlap accounts for a relatively small proportion of the variation in liability between these disorders (e.g., the correlations of 0.29-0.37 translate to an overlap of 9-14%; of this overlap, 50-60% is attributed to shared genetic factors and the remainder to specific environmental factors). The significant contribution of sex-specific processes may explain the lack of consistency in the results from previous studies.
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