Brain GABA levels are reduced in alcoholic liver disease: A proton magnetic resonance spectroscopy study

Addict Biol. 2020 Jan;25(1):e12702. doi: 10.1111/adb.12702. Epub 2018 Dec 18.

Abstract

Background and aims: Baclofen, a selective γ-aminobutyric acid (GABA)B receptor agonist, has emerged as a potential treatment for alcohol use disorder with much unexplained variation in response to treatment efficacy and dose regimen. Several positive studies include patients with alcoholic liver disease (ALD) and/or history of heavy drinking. The aim of this paper was to examine the association of cortical GABA+ concentration with severity of liver disease (including markers of liver injury) and other clinical characteristics in alcohol patients.

Methods: Proton magnetic resonance spectroscopy (1 H-MRS), from the parietal lobe, was analyzed to yield absolute concentration of GABA in 24 alcohol-dependent individuals. Diagnosis of ALD, markers of liver injury, severity of liver disease (Model for End-Stage Liver Disease [MELD]), and alcohol history were assessed. Covariates included concurrent medication, age, and recent alcohol consumption.

Results: Multiple linear regression revealed that GABA+ concentration was significantly predicted by MELD scores (F = 5.02, R2 = 0.59, P = 0.01; MELD: B = -0.63, P = 0.02), when controlling for covariates concurrent medication, age, and recent alcohol consumption.

Conclusion: Severity of ALD is associated with lower cortical concentrations of GABA+. These results may explain variations in response to the GABAB agonist, baclofen, in the alcohol-dependent population.

Trial registration: ClinicalTrials.gov NCT01711125.

Keywords: GABA; alcohol dependence; alcohol liver disease; baclofen.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Baclofen / pharmacokinetics*
  • Baclofen / therapeutic use*
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Double-Blind Method
  • Female
  • GABA-B Receptor Agonists / pharmacokinetics
  • GABA-B Receptor Agonists / therapeutic use
  • Humans
  • Liver Diseases, Alcoholic / drug therapy*
  • Male
  • Middle Aged
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • GABA-B Receptor Agonists
  • Baclofen

Associated data

  • ClinicalTrials.gov/NCT01711125