Brain Glutamate, GABA, and Glutamine Levels and Associations with Recent Drinking in Treatment-Naïve Individuals with Alcohol Use Disorder Versus Light Drinkers

Abstract

Background: Proton magnetic resonance spectroscopy (¹ H-MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in inpatients/outpatients with alcohol use disorder (AUD) following acute alcohol withdrawal relative to healthy controls. In contrast, few studies have compared neurometabolite levels between less severe, treatment-naïve AUD individuals and light drinkers (LD) or related them to recent alcohol consumption. The present study compared neurometabolite levels between treatment-naïve AUD and LD individuals.

Methods: Twenty treatment-naïve individuals with AUD and 20 demographically matched LD completed an ¹ H-MRS scan, approximately 2.5 days following their last reported drink. ¹ H-MRS data were acquired in dorsal anterior cingulate (dACC) using a 2-dimensional J-resolved point-resolved spectroscopy sequence. dACC neurometabolite levels, with a focus on glutamate, glutamine, and GABA, were compared between AUD and LD participants. The associations between metabolite levels and recent drinking were explored.

Results: AUD participants had significantly lower concentrations of GABA (Cohen's d = 0.79, p = 0.017) and glutamine (Cohen's d = 1.12, p = 0.005), but not glutamate (Cohen's d = 0.05, p = 0.893), relative to LD. As previously reported, AUD participants' glutamate and N-acetylaspartate concentrations were inversely associated with their number of heavy drinking days. In contrast, neither number of drinking (mean p = 0.56) nor heavy drinking (mean p = 0.47) days were associated with metabolite concentrations in LD.

Conclusions: The present study demonstrated significantly lower levels of prefrontal γ-aminobutyric acid and glutamine in treatment-naïve individuals with AUD relative to LD. Whether these findings reflect the neurotoxic consequence and/or neuroadaptive response of alcohol consumption versus a predrinking trait, and therefore a more durable neurochemical disturbance, awaits elucidation from longitudinal studies.

Keywords: Alcohol Use Disorder; GABA; Glutamine; Magnetic Resonance Spectroscopy; Treatment Naïve.