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Adoption Study Demonstrating Two Genetic Pathways to Drug Abuse

Remi J. Cadoret, MD; William R. Yates, MD; Troughton Ed, PhD; George Woodworth, PhD; Mark A. Stewart, MD
Arch Gen Psychiatry. 1995;52(1):42-52. doi:10.1001/archpsyc.1995.03950130042005.
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Background:  Studies of adoptees have demonstrated that there are two genetic factors leading to alcohol abuse and/or dependence (abuse/dependence). In addition, environmental factors found in the adoptive family also predict alcohol abuse/dependency independently. One study has found evidence that a similar model of two genetic factors and independent adoptive family factors were involved in drug abuse. Our study was designed to test the hypothesis that genetic factors defined by alcohol abuse/dependency and antisocial personality disorder in biologic parents were etiologic in drug abuse/dependency and that psychiatric problems in adoptive parents were an additional factor associated with drug abuse/dependence.

Methods:  A sample of 95 male adoptees, separated at birth from their biologic parents, were followed up as adults to determine their psychiatric diagnosis and their substance use/abuse in a structured interview administered blind to biologic parent diagnoses. A high-risk, case-control design was used wherein half of the adoptees came from biologic parents known to be alcohol abuser/dependent and/or have antisocial personalities (diagnoses from hospital or prison records). These adoptees were matched for age, sex, and adoption agency to a control group of adoptees whose biologic parents were not found in the hospital and prison record search. Adoptive home environment was assessed by structured interviews, including psychiatric assessment of both adoptive parents.

Results:  Data were analyzed by log-linear modeling, which showed evidence of two genetic pathways to drug abuse/dependency. One pathway went directly from a biologic parent's alcoholism to drug abuse/dependency. The second pathway was more circuitous, and started with antisocial personality disorder in the biologic parent and proceeded through intervening variables of adoptee aggressivity, conduct disorder, antisocial personality disorder, and, eventually, ended in drug abuse/dependency. Environmental factors defined by psychiatric conditions in adoptive families independently predicted increased antisocial personality disorder in the adoptee. Adoptees born of alcohol-abusing mothers showed evidence of fetal alcohol syndrome, but controlling for this did not diminish the evidence for the direct genetic effect between an alcohol-abusing biologic parent and drug abuse/dependency in offspring.

Conclusions:  This study confirms the model of two independent genetic factors involved in drug abuse/dependence and previous findings that disturbed adoptive parents are associated with adoptee drug abuse/dependency.

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