title: 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.
authors.affiliation: Department of Psychiatry & Behavioral Neuroscience, University of Chicago, Chicago, Illinois. Electronic address: aking@bsd.uchicago.edu.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: King
authors.affiliation: Department of Psychiatry, Mailman School of Public Health, Department of Epidemiology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Deborah
authors.initials: D
authors.lastname: Hasin
authors.affiliation: Departments of Psychiatry and Biomedical Engineering, Indiana University School of Medicine and Purdue University, Indianapolis, Indiana.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: O'Connor
authors.affiliation: Department of Psychiatry & Behavioral Neuroscience, University of Chicago, Chicago, Illinois.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McNamara
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Dingcai
authors.initials: D
authors.lastname: Cao
mesh_terms: D000328:Adult; D000435:Alcoholic Intoxication / Q000523:psychology*; D000437:Alcoholism / Q000523:psychology*; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006993:Hypnotics and Sedatives; D008297:Male; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012201:Reward; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D000431:Ethanol; D006854:Hydrocortisone
keywords: Alcohol response; Heavy drinking progressing with AUD; Reward sensitivity; Stimulation; Subjective; Tolerance