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Kenneth S. Kendler, MD; John Myers, MS; Carol A. Prescott, PhD

Arch Gen Psychiatry. 2007;64(11):1313-1320.

Context  Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate.

Objective  To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females.

Design  Lifetime history by structured clinical interview.

Setting  General community.

Participants  Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.

Main Outcome Measure  Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine.

Results  Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor—loading only on cannabis and cocaine—and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine.

Conclusions  The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors—one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence—are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence appear to be specific to those substances.

Author Affiliations: Virginia Institute of Psychiatric and Behavioral Genetics (Dr Kendler and Mr Myers), and Departments of Human Genetics (Dr Kendler) and Psychiatry (Dr Kendler and Mr Myers), Medical College of Virginia, Virginia Commonwealth University, Richmond; and Department of Psychology, University of Southern California, Los Angeles (Dr Prescott).

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