Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol

Alcohol. 2014 Nov;48(7):631-8. doi: 10.1016/j.alcohol.2014.08.007. Epub 2014 Aug 27.


Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned.

Keywords: Alcohol; BDNF; Genetics; Hippocampus; MRI; Smoking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Abstinence* / psychology
  • Alcoholism / genetics
  • Alcoholism / pathology*
  • Alcoholism / psychology
  • Brain-Derived Neurotrophic Factor / genetics
  • Case-Control Studies
  • Female
  • Genotype
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging
  • Neuropsychological Tests
  • Organ Size / drug effects
  • Polymorphism, Single Nucleotide / genetics
  • Smoking / adverse effects


  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human