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

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.

• Authors: Kirsten C Morley, Jim Lagopoulos, Warren Logge, Andrew Baillie, Claire Adams, Paul S Haber
• Journal: Addiction biology (Addict Biol) Vol. 25 Issue 1 Pg. e12702 (01 2020) ISSN: 1369-1600 [Electronic] United States
• PMID: 30561840 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Society for the Study of Addiction.

Chemical References

• GABA-B Receptor Agonists
• Baclofen

Topics

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