Is there a genetic relationship between alcoholism and depression? - Research Update

Alcohol Research & Health, Fall, 2002 by John I. Nurnberger, Jr., Tatiana Foroud, Leah Flury, Eric Meyer, T., Ryan Wiegand

It has long been known that alcoholism and depression tend to occur together and that both disorders may run in families. Researchers participating in the Collaborative Study on the Genetics of Alcoholism (COGA) have investigated the prevalence of alcoholism and depression in alcoholic participants and their family members. According to Dr. John I. Nurnberger, Jr., and his colleagues, these analyses found that the prevalence of depressive syndrome (i.e., depression that may or may not occur in conjunction with increased drinking) was higher among alcoholics than among nonalcoholics. Moreover, both disorders co-occurred more commonly among family members of people with both disorders than among family members of people with alcoholism alone. (pp. 233-240)

The Collaborative Study on the Genetics of Alcoholism (COGA) seeks to identify genes contributing to alcoholism and related traits (i.e., phenotypes), including depression. Among alcoholic subjects the COGA study found an increased prevalence of depressive syndrome (i.e., depression that may or may not occur in conjunction with increased drinking). This combination of alcoholism and depression tends to run in families. Comorbid alcoholism and depression occurred substantially more often in first, degree relatives of COGA participants with alcoholism than in relatives of control participants. Based on these data, COGA investigators defined three phenotypes--"alcoholism," "alcoholism and depression," and "alcoholism or depression"--and analyzed whether these phenotypes were linked to specific chromosomal regions. These analyses found that the "alcoholism or depression" phenotype showed significant evidence for genetic linkage to an area on chromosome 1. This suggests that a gene or genes on chromosome 1 may predispose some people to alcoholism and others to depression (which may be alcohol induced). KEY WORDS: genetic theory of AODU (alcohol and other drug use); AOD dependence; genetic trait; major depression; mood and affect disturbance; comorbidity; phenotype; chromosome; AODR (alcohol and other drug related) genetic markers; prevalence; gender differences; genetic linkage

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It is obvious to drinkers that a direct connection exists between alcohol consumption and mood. Alcoholic intoxication commonly produces a "high" with attendant giddiness and lowering of inhibitions. Conversely, hangovers and acute withdrawal typically produce dysphoria, with elements of anxiety and depression mixed with physical malaise. Psychopathological studies have observed that alcoholism and affective disorders (e.g., depression and mania) interact and can coexist; moreover, the vulnerability to both alcoholism and depression can run in families (Merikangas and Gelernter 1990; Merikangas et al. 1994).

Various possible relationships between alcoholism and affective disorders have been postulated (see table 1) (for more information, see Nurnberger and Berrettini 1998; Merikangas and Gelernter 1990). For instance, some patients may use alcohol as a form of self-medication for an affective disorder. In these cases, alcoholism may develop secondarily to the affective disorder. Alternatively, depression may develop as a result of alcoholism; in these cases, alcoholism is the primary disorder and depression is considered an organic mood disorder (i.e., a mood disorder with a physiological cause). Other alternatives are that both alcoholism and affective disorder may develop as the result of a common genetic predisposition or may develop as completely separate illnesses. These different hypotheses about the relationship between alcoholism and affective disorders have different implications for the prevalence of these illnesses in family studies (see table 1). For example, if alcoholism were the primary disorder and depression occurred as a result of it, relatives of alcoholics would be expected to have an increased risk of alcoholism with secondary depression but not of depression alone. Relatives of people with depression but without alcoholism would be expected to have an increased risk of depression only. However, if depression were the primary disorder and alcoholism occurred secondarily to it, relatives of nondepressed alcoholics would be expected to have an increased risk of alcoholism only, whereas relatives of people with depression would be expected to have an increased risk of depression with secondary alcoholism.

Family data, such as those discussed later in this article, so far have not been entirely consistent with any single hypothesis but have suggested that several mechanisms may contribute to the relationship between alcoholism and affective disorders. Nevertheless, such analyses have confirmed that an association between alcoholism and affective disorders exists and that this association is at least partly mediated by genetic factors. The Genetics Initiative of the National Institute of Mental Health (NIMH) found that among families selected for multiple cases of bipolar disorder, males with major affective disorder had nearly twice the risk for alcoholism compared with males without affective disorder. Among females, the risk was raised sevenfold (Nurnberger and the NIMH Genetics Initiative Bipolar Group 2001). Kendler and colleagues (1993), who studied the co-occurrence of alcoholism and major depression in female twins, found a substantial genetic correlation (correlation coefficient of 0.4 to 0.6) between the two disorders.