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

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.

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.

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.

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