The role of alcohol response phenotypes in the risk for alcohol use disorder

Abstract

Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol ('low-level response') imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk. This study presents results of a unique longitudinal study in 294 young adult non-dependent drinkers examined with alcohol and placebo testing in the laboratory at initial enrolment and repeated 5 years later, with regular follow-up intervals assessing AUD (trial registration: https://ichgcp.net/clinical-trials-registry/NCT00961792). Findings showed that alcohol sedation was negatively correlated with stimulation across the breath alcohol curve and at initial and re-examination testing. A higher rather than lower alcohol response phenotype was predictive of future AUD. The findings underscore a new understanding of factors increasing vulnerability to AUD.

Keywords: Alcohol; differentiator model; low-level response theory; sedation; stimulation.

Figures

Fig. 1

(a) Scatterplots and Pearson correlation between alcohol sedation (x-axis) and stimulation (y-axis) change scores calculated for the alcohol minus placebo session responses for the whole sample at initial testing at peak breath alcohol concentration (BrAC). (b) Bar graph of the frequency of participants with alcohol use disorder (AUD+) who were initially high- and low-alcohol responders at peak BrAC (change scores from placebo >0 for stimulation, <0 for sedation).