A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder

Abstract

Background: The main neurobiological theories of the development of addiction, including tolerance, sensitization, incentive-sensitization, and allostasis, have not been tested in longitudinal human alcohol response research. To address this issue, we conducted the first controlled prospective investigation of subjective and neuroendocrine responses to alcohol measured over a 5-year interval in at-risk young adult heavy drinkers (HD) and light drinker control subjects.

Methods: Participants were 156 individuals, 86 heavy drinkers and 70 light drinkers, undergoing an initial oral alcohol challenge testing (.8 g/kg alcohol vs. placebo) and an identical re-examination testing 5 to 6 years later. Alcohol use disorder (AUD) symptoms and drinking behaviors were assessed in the interim follow-up period.

Results: At re-examination, HD continued to exhibit higher sensitivity on alcohol's stimulating and rewarding effects with lower sensitivity to sedative effects and cortisol reactivity, relative to light drinkers. In HD with high AUD symptom trajectories over follow-up, heightened alcohol stimulation and reward persisted at re-examination. HD with low AUD symptoms showed reduced alcohol stimulation over time and lower reward throughout compared with the HD with high and intermediate AUD symptoms.

Conclusions: Results support the early stage phase of the allostasis model, with persistently heightened reward sensitivity and stimulation in heavy drinkers exhibiting AUD progression in early mid-adulthood. While there are multiple pathways to development of a disorder as complex as AUD, maintenance of alcohol stimulatory and rewarding effects may play an important role in the continuation and progression of alcohol addiction.

Trial registration: ClinicalTrials.gov NCT00961792.

Keywords: Alcohol response; Heavy drinking progressing with AUD; Reward sensitivity; Stimulation; Subjective; Tolerance.

Conflict of interest statement

All other authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

BrAC curve data as mean (SEM) for light and heavy drinkers at initial and re-examination testing.

Figure 2

Figure 2A–C. Alcohol stimulation, liking and wanting at initial and re-examination phases. Data are shown for light (n=70) and heavy drinker groups (n=86), as well the heavy drinker AUD trajectory subgroups, including low AUD (n=26), intermediate AUD (n=51), and high AUD (n=9). Fig 2A is the net change score (alcohol session peak BrAC minus baseline change score minus the same change score for the placebo session) for the BAES stimulation; three outliers (

Figure 3

Figure 3A–B. Alcohol sedation and cortisol response at initial and re-examination phases. Data are shown for light (n=70) and heavy drinker groups (n=86), as well the heavy drinker AUD trajectory subgroups, including low AUD (n=26), intermediate AUD (n=51), and high AUD (n=9). Fig 3A is the net change score (alcohol session peak BrAC minus baseline change score minus the same change score for the placebo session) for the BAES sedation and Fig 3B is the net change score (alcohol session 180 minutes minus baseline change score minus the same change score for the placebo session) for salivary cortisol levels; three outliers (two > 3 SD above mean, one