Dopaminergic Genes in Relation to Alcohol Expectancies through Early Adolescence in Taiwan

Introduction: Alcohol expectancies (AEs), the belief toward the reward of alcohol drinking, is a prominent cognitive predictor for alcohol drinking and problems in community-based and clinical studies. The transition from childhood to adolescence is a critical period not only for positive AEs development but also for rapid growth/change in brain’s reward circuit. The goals of the present study were to examine the extent to which dopaminergic genetic predisposition affects (i) the endorsed AEs in late childhood and (ii) the changes in AEs through early teenage years.

Methods: Data on sociodemograhics, childhood-onset drinking, pro-alcohol social context (e.g., parental alcohol drinking), and AEs were ascertained from 2630 primary school-attending children (aged 10-12) in the academic year of 2006 (response rate = 60.1%); two waves of assessment were conducted annually (follow-up rates > 80%). AEs covered three positive: Global Positive Transformation [GPT], Enhanced Social Behaviors [ESB], and Promoting Relaxation or Tension Reduction [PRTR]; one negative: Deteriorated cognitive and behavioral function [DCBF] (all cronbach’s alpha > 0.7). 1084 had provided saliva for DNA retrieval (response rate: 58.4%_wt) and the polymorphisms of DRD2 (rs1799978, rs6277), DRD3 (rs6280), and DRD4 (rs1800955) were genotyped. Using the dopaminergic polygenic risk scores, a proxy for additive effects of alleles, we performed the Generalized Linear Model to estimate the connection linking dopaminergic markers with endorsed AEs, with stratified by childhood-onset drinking.

Results: At baseline, a total of 381 (36.0% _wt) children had tried alcohol, and three domains of positive AEs for the alcohol experienced were significantly greater than the alcohol naïve (p<0.01). During the two-year follow-up, 24.9% _wt initiated alcohol drinking and the change in positive AEs was particularly prominent for the ESB (mean= 0.21). With statistical adjustment for sociodemographics and pro-alcohol social contexts, having higher dopaminergic genetic scores was manifested in negative AE (DCBF: β_wt = -1.80; 95% CI = -3.45, -0.16) for those alcohol experienced (both childhood- and adolescence-onset).

Conclusion: The association linking dopamine receptor phenotype with negative alcohol expectancies varied by childhood-onset drinking. Our results indicated that prevention/intervention programs reducing underage drinking problems should better understand the role of genetics while developing strategies tackling cognitive pathways.