Alcohol-related expectancies are associated with the D2 dopamine receptor and GABAA receptor β3 subunit genes

Molecular genetic research has identified promising markers of alcohol dependence, including alleles of the D-2 dopamine receptor (DRD2) and the GABA(A) receptor beta3 subunit (GABRB3) genes. Whether such genetic risk manifests itself in stronger alcohol-related outcome expectancies, or in difficulty resisting alcohol, is unknown. In the present study, A1+ (A1A1 and A1A2 genotypes) and A1-(A2A2 genotype) alleles of the DRD2 and G1+(G1G1 and G1 non-G1 genotypes) and G1-(non-G1 non-G1 genotype) alleles of the GABRB3 gene were determined in a group of 56 medically ill patients diagnosed with alcohol dependence. Mood-related alcohol expectancy (AE) and drinking refusal self-efficacy (DRSE) were assessed using the Drinking Expectancy Profile (Manual for the Drinking Expectancy Profile, Behaviour Research and Therapy Centre, Brisbane, 1996). Patients with the DRD2 A1+ allele, compared with those with the DRD2 A1 - allele, reported significantly lower DRSE in situations of social pressure. Similarly, lower DRSE was reported under social pressure by patients with the GABRB3 G1+ allele when compared to those with the GABRB3 G1 - alleles. Patients with the GABRB3 G1+ allele also revealed reduced DRSE in situations characterized by negative affect than those with the GABRB3 G1 - alleles. Patients carrying the GABRB3 G1+ allele showed stronger AE relating to negative affective change (for example, increased depression) than their GABRB3 G1 - counterparts. Biological influence in the development of some classes of cognitions is hypothesized. The clinical implications, particularly with regard to patient-treatment matching and the development of an integrated psychological and pharmacogenetic approach, are discussed. (C) 2004 Elsevier Ireland Ltd. All rights reserved.