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

Abstract

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. Twenty treatment-naïve individuals with AUD and 20 demographically matched LD completed an 1 H-MRS scan, approximately 2.5days 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. 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. 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.