Neurometabolite levels in alcohol use disorder patients during baclofen treatment and prediction of relapse to heavy drinking

Kirsten C. Morley*, Jim Lagopoulos, Warren Logge, Kate Chitty, Andrew Baillie, Paul S. Haber

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background and Aims: Baclofen, a GABAB agonist, is used as a treatment for alcohol dependence. We aimed to examine brain metabolites following administration of baclofen or placebo in alcohol dependent individuals enrolled in a randomized placebo-controlled trial. Methods: Participants included 31 alcohol dependent individuals (recent drinking: N = 16; and abstinent: N = 15) who had received daily baclofen (BAC 30-75 mg = 20) or placebo (PL = 11) for at least 2 weeks (average 17 days). Using in vivo proton magnetic resonance spectroscopy (1H-MRS), spectra from the right parietal lobe were analyzed to obtain measures of GABA, Glutamate (Glu), Glutathione (GSH) and N-Acetyl Apartate (NAA) 120 min following administration of PL or BAC. Results: When weighting alcohol dependent participants according to recent alcohol consumption (within 24 h), there were significant differences between BAC and PL on parietal concentrations of GSH (p < 0.01) and NAA (p < 0.05). Multiple linear regression revealed a significant predictive effect of GSH on heavy drinking days at 12 weeks follow-up (Model: F = 14.28, R2 = 0.85; GSH: B = -1.22, p = 0.01) and also percentage days abstinent at 12 weeks follow-up (Model: F = 6.50, R2 = 0.72; GSH: B = 0.99, p = 0.06). Conclusion: Our data provide preliminary evidence that the effect of baclofen may be mediated by increased parietal concentrations of the antioxidant GSH and NAA in recently drinking alcohol dependent patients. GSH/Cr levels were also predictive of improved drinking outcomes in the trial and suggests a role for neural oxidative stress in alcohol use disorder.

Original languageEnglish
Article number412
Pages (from-to)1-8
Number of pages8
JournalFrontiers in Psychiatry
Volume9
Issue numberSEP
DOIs
Publication statusPublished - 4 Sep 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • GABA
  • glutamate
  • GSH
  • NAA
  • baclofen
  • alcohol dependence

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