Carla Williams, Ph.D., Principal Investigator, Department of Psychology
Behavioral Genetics of Alcoholism and Cigarette Smoking

ABSTRACT

SIGNIFICANCE: Alcohol dependence and chronic cigarette smoking are commonly co-occurring disorders. Some individuals who are dependent on one substance may have biological and psychosocial predispositions toward dependence on both drugs. Both tobacco and alcohol use have been associated with cancer of the mouth, pharynx, and esophagus. The long-term combined use of these substances may synergistically increase cancer risk.

RATIONALE: Polymorphisms of the D2 dopamine (DRD2) receptor gene may result in a blunting of the brain's natural reward circuitry. A poorly functioning natural reward system may substantially reduce one’s ability to derive a sense of gratification from rewarding experiences such as personal successes, effectively solving day-to-day problems, or successfully managing difficult situations. The ability to benefit from the intrinsic rewards associated with successful coping and goal attainment may be integral to recovery from drug use disorders. There is some evidence linking the DRD2A1 allele to lower dopamine receptor density and/or lower binding affinity for dopamine. Some individuals with compromised functioning of dopaminergic reward pathways may find it more difficult to forego the instant gratification of nicotine and alcohol in lieu of the natural rewards that come from effectively coping with daily stresses. Because motivation to repeatedly employ effective coping skills is a central component of substance abuse recovery, the role of the DRD2 receptor gene may possibly have important implications for remission of substance dependence.

AIMS: The proposed study will use a cross-sectional design to examine how recovery from combined alcoholism and chronic cigarette smoking may be influenced by polymorphisms in the DRD2 gene. This study will seek to determine whether this gene is associated with a distinguishable phenotype expressed through personality characteristics and behavioral traits that directly impact recovery.

METHOD: A sample of African American adults with and without a history of concurrent alcoholism and chronic cigarette smoking will be recruited to participate in the proposed study. Participants will be classified into three groups: Active Cases, Remission Cases, and Controls. Interview data and blood samples will be collected from all participants. Study participants will complete a standardized personality assessment, measures of coping style, coping adequacy, and general psychosocial functioning. Detection of polymorphisms at the D2 dopamine receptor gene will be accomplished by PCR-RFLP. Data will be analyzed to determine the independent and combined contributions of genetic and psychosocial attributes to remission status.