Epidemiologic studies find that individuals rarely abuse a single substance. Instead, polysubstance abuse/dependence is normative, with high rates of comorbidity across various drug classes. In addition, persons with substance use disorders also exhibit higher rates of other psychiatric disorders including mood disorders and antisocial personality disorder. Twin studies suggest that this comorbidity is due at least in part to a shared genetic cause underlying susceptibility to different types of substance use and other psychopathologies. Kendler and colleagues36 used the Virginia Twin Registry sample to identify common genetic factors underlying the major class of psychiatric and substance use disorders, and found that a common genetic factor was shared across alcohol dependence, illicit drug dependence, adult antisocial behavior, and childhood conduct disorder. These results suggest a common genetic factor for substance dependence/abuse and general externalizing psychopathologies (Fig. 1). Alcohol dependence and illicit drug dependence also showed some disorder-specific genetic influences. However, 69% of the total genetic variance on alcohol dependence, and 64% of the genetic variance on illicit drug dependence resulted from the genetic factor shared across externalizing psychopathology. This finding indicates
