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

Winokur and colleagues (1971) postulated that depressive illness could be divided into four types, depending on familial pattern of illness. These included (1) sporadic depressive disorder, which was nonfamilial; (2) pure depressive disorder, in which depression (but not alcoholism or sociopathy) was found in several relatives; (3) depressive spectrum disorder, in which depression as well as alcoholism or sociopathy was found in relatives of depressed subjects; and (4) bipolar depression, which was found in families with bipolar illness. It is of interest that the families examined in the Collaborative Study on the Genetics of Alcoholism (COGA), which is described in detail below, show an increased risk for sociopathy as well; interactions between depression and alcoholism, including the role of sociopathy, will be the subject of future analyses (Nurnberger et al. 2002). Investigators found various clinical distinctions among patients with these different types of depression. Perhaps the most impressive data were gathered by Schlesser and colleagues (1979), who found that people with pure depressive disorder showed a different pattern of activity of the stress hormone system (i.e., the hypothalamic-pituitary-adrenal system) than did people with depressive spectrum disorder or sporadic depression.

Thus, it appears likely that both alcoholism and depression exist in various forms (i.e., are heterogeneous) and that the co-occurrence (i.e., comorbidity) of both disorders may have different underlying mechanisms as well. Findings with animal models that have examined alcohol consumption and "depressive" behavior have also been heterogeneous. (For more information on such animal models, see the sidebar.) At this point, it is difficult to identify subtypes of both disorders on the basis of clinical criteria alone. Genetic studies such as COGA, however, may help with this distinction.

The COGA project, conducted at several research centers across the United States, seeks to identify genes contributing to the development of alcoholism and related characteristics (i.e., phenotypes). This article describes some of the methods used by COGA investigators to define phenotypes related to the comorbidity of alcoholism and depression and summarizes data on both disorders in the COGA participants. Finally, the article discusses the implications of these findings for a potential genetic relationship between alcoholism and depression.

DESIGN AND METHODS OF THE COGA STUDY

Between 1988 and 1998, investigators at six COGA sites used a common protocol to gather clinical information and biological data (including DNA and neurophysiologic measures) from families of subjects with alcoholism. Participants were recruited among patients undergoing alcoholism treatment (i.e., the probands) and their first-degree relatives. Control families were recruited from dental clinics, motor vehicle records, or random mailings at the six sites. Control families were not excluded if a family member had alcoholism or another psychiatric disorder; thus, these families represent a comparison group not selected with respect to psychopathology. Each control family included at least two parents and three children ages 14 and older. All participants were interviewed using a screening instrument called the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) (Bucholz et al. 1994), which allows for diagnostic assessment of various disorders, including alcoholism and depression.