Alcoholic Subtype, Treatment Outcome, and Genotype

Galen, Luke

Abstract

One of the primary rationales for the development of alcoholism typologies, and for the identification of alcoholism vulnerability alleles, is to reduce heterogeneity among alcoholism subtypes and to provide treatment that is individualized and effective. Because the serotonin and dopamine neurotransmitter systems have been implicated in the genetic etiology of alcoholism, as well as being systems modifiable by pharmacological agents shown to be effective in treating other psychopathology, they are logical systems on which to focus with respect to treatment outcome. Increased understanding of the associations among neurotransmitter systems, alcoholism typology and treatment outcome should provide information critical to treatment matching. This collaborative project, to be conducted jointly by the applicant and a behavior geneticist, has the following specifications: (1) To assess whether particular genotypes have an effect on treatment outcome (i.e., percent days abstinent, substance-related problems). (2) To assess whether the effect of genotype on treatment outcome is mediated by temperament, specifically in areas having to do with novelty seeking (NS), harm avoidance (HA), and reward dependence (RD). A minimum of 300 participants (190 men and 110 women) will be recruited as consecutive admissions to an outpatient treatment center. On intake, participants will self-administer a questionnaire battery assessing alcohol use and the NS and HA temperament dimensions, and will donate 7 ml of blood for genetic analysis. Following the intake assessment, a six month follow- up interview will assess alcohol and drug consumption patterns to evaluate treatment efficacy. We will assay four genetic markers thought to be logical candidates for associations with either temperament and/or with alcoholism: serotonin transporter (5HTT), serotonin 2c receptor (HTR2C), monoamine oxidase A (MAOA), and dopamine receptor D4 (DRD4). Results of this research will be a first step in increasing understanding of the associations among neurotransmitter systems, alcoholism typology and treatment outcome.