Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype

Sarah W. Yip, Joanne Doherty, Judi Wakeley, Kate Saunders, Charidimos Tzagarakis, Harriet De Wit, Guy M. Goodwin, Robert D. Rogers

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Elevated lifetime prevalence rates of alcohol use disorders (AUDs) are a feature of bipolar disorder (BD). Individuals at-risk for AUDs exhibit blunted subjective responses to alcohol (low levels of response), which may represent a biomarker for AUDs. Thus, individuals at-risk for BD may exhibit low responses to alcohol. Participants were 20 unmedicated adult males who reported high rates of hypomanic experiences (bipolar phenotype participants; BPPs), aged 18 to 21 years, and 20 healthy controls matched on age, gender, IQ, BMI, and weekly alcohol intake. Subjective and pharmacokinetic responses to acute alcohol (0.8 g/kg) vs placebo administration were collected in a randomized, double-blind, cross-over, placebo-controlled, within-subjects design. BPP participants reported significantly lower subjective intoxication effects ('feel high': F=14.2, p=0.001; 'feel effects': F=8.1, p=0.008) across time, but did not differ in their pharmacokinetic, stimulant, or sedative responses. Paradoxically, however, the BPP participants reported significantly higher expectations of the positive effects of alcohol than controls. Our results suggest that unmedicated young males with previous hypomanic experiences exhibit diminished subjective responses to alcohol. These blunted alcohol responses are not attributable to differences in weekly alcohol intake, pharmacokinetic effects (eg, absorption rates), or familial risk of AUDs. These observations suggest that the dampened intoxication may contribute to the increased rates of alcohol misuse in young people at-risk for BD, and suggest possible shared etiological factors in the development of AUDs and BD.

Original languageEnglish (US)
Pages (from-to)1808-1815
Number of pages8
Issue number8
StatePublished - Jul 2012

Bibliographical note

Funding Information:
Guy M Goodwin holds or has held grants from Bailly Thomas charity, Medical Research Council, NIHR, Servier; has received honoraria from AstraZeneca, BMS, Lundbeck, Sanofi-Aventis, Servier, holds shares in P1vital; has served on advisory boards for AstraZeneca, BMS, Boehringer Ingelheim, Cephalon, Janssen-Cilag, Lilly, Lundbeck, P1Vital, Servier, Shering Plough, Wyeth and acted as an expert witness for Lilly and Servier. Harriet De Wit has received funding from the National Institutes of Health, and for a research study unrelated to this project from Unilever within the last three years. The remaining authors declare no conflict of interest.

Funding Information:
Financial support for this research was provided by the Medical Research Council (MRC) and the Oxford University Clinical Academic Graduate School (OUCAGS). The authors have no other acknowledgements.


  • adolescence
  • alcohol abuse/dependence
  • bipolar disorder
  • ethanol
  • hypomania
  • mood


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