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

Background Proton magnetic resonance spectroscopy (1H‐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 1H‐MRS scan, approximately 2.5 days following their last reported drink. 1H‐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. Treatment‐naïve individuals with Alcohol Use Disorder (n = 20, M[SD] Age = 26.8[6.2]) had significantly lower levels of dorsal Anterior Cingulate Cortex GABA (Cohen's‐D = 0.79) and Glutamine (Cohen's‐D = 1.12) relative to demographically‐matched light‐drinkers via Proton Magnetic Resonance Spectroscopy. These results are important because they demonstrate AUD‐associated neurochemical disturbances in a younger/less severe sample than has previously been studied with 1H‐MRS. If replicated, these findings may lead t