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Kathleen R. Merikangas, PhD; Marilyn Stolar, MA; Denise E. Stevens, PhD; Joseph Goulet, MS; Martin A. Preisig, MD; Brenda Fenton, PhD; Heping Zhang, PhD; Stephanie S. O'Malley, PhD; Bruce J. Rounsaville, MD

Arch Gen Psychiatry. 1998;55:973-979.

Background  There is increasing evidence that substance use disorders are familial and that genetic factors explain a substantial degree of their familial aggregation. To perform a controlled family study of probands with several different predominant drugs of abuse, including opioids, cocaine, cannabis, and/or alcohol.

Methods  The subjects for the present study included 231 probands with dependence on opioids, cocaine, cannabis, and/or alcohol and 61 control probands, and their 1267 adult first-degree relatives. Diagnostic estimates were based on semistructured diagnostic interviews and/or structured family history interviews regarding each proband, spouse, and adult first-degree relative. The interview data were reviewed blindly and independently by clinicians with extensive experience in the evaluation and treatment of substance use disorders.

Results  There was an 8-fold increased risk of drug disorders among the relatives of probands with drug disorders across a wide range of specific substances, including opioids, cocaine, cannabis, and alcohol, which is largely independent from the familial aggregation of both alcoholism and antisocial personality disorder. There was also evidence of specificity of familial aggregation of the predominant drug of abuse.

Conclusions  Elevation in risk of this magnitude places a family history of drug disorder as one of the most potent risk factors for the development of drug disorders. These results suggest that there may be risk factors that are specific to particular classes of drugs as well as risk factors that underlie substance disorders in general.

From the Departments of Epidemiology and Public Health (Drs Merikangas, Stevens, and Zhang, Ms Stolar, and Mr Goulet) and Psychiatry (Drs Merikangas, O'Malley, and Rounsaville), Yale University School of Medicine, New Haven, Conn; Department of Psychiatry, University of Lausanne, Lausanne, Switzerland (Dr Preisig); and Department of Psychiatry, University of Geneva, Geneva, Switzerland (Dr Fenton).

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