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 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 Two-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. 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 reported in Prisciandaro et al. (2016), AUD participants' glutamate and NAA 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 GABA 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 pre-drinking trait, and therefore a more durable neurochemical disturbance, awaits elucidation from longitudinal studies.

Intraindividual changes in brain GABA, glutamate, and glutamine during monitored abstinence from alcohol in treatment‐naive individuals with alcohol use disorder

“…Unlike Prisciandaro et al, 20 no differences were found in glutamine levels between AUD and light drinkers at the initial scan. We concentrated initial speculation concerning why this finding did not replicate in the present study on the primary difference between the two studies: number of days since last drink at baseline.…”

“…Twenty‐three individuals with AUD and 12 demographically matched LD were recruited from community advertisements; an additional eight LD participants (ie, females with relatively fewer years of education) were selected from Prisciandaro and colleagues' LD sample 20 to demographically match LD and AUD participants for baseline group comparisons. AUD participants from the present study and Prisciandaro et al (2018) also appear in a concurrently published investigation of brain glycine levels in AUD participants 21 .…”

“…drawal symptoms) at <1 and/or 3 days post final drink, followed by decreased glutamate levels at 7 days post final drink, the population at hand was unlikely to report significant alcohol withdrawal symptoms. 19 In contrast, given that the two available 1 H-MRS studies of relatively low severity, treatment-naïve AUD individuals have both found them to have significantly lower levels of prefrontal GABA relative to light drinkers, 16,20 we predicted that initial GABA levels would be significantly lower in AUD versus LD and that there would be significant change in GABA levels across scans in AUD but not LD. Prospective associations between changes in GABA, glutamate, and glutamine levels and changes in alcohol consumption, craving, and withdrawal across scan visits were also explored.…”

“…were conducted using AUD (n = 23) and LD (n =20) baseline and scan 1 data to evaluate the replicability of results reported in Prisciandaro et al 19,20. Specifically, following characterization of demographic and clinical variables between groups, general linear models (GLM) were evaluated, one per estimated metabolite (glutamate, glutamine, and GABA), with group (AUD vs LD) included as a between-subjects factor.…”

Prehabilitation in Alcohol Dependence as a Treatment Model for Sustainable Outcomes. A Narrative Review of Literature on the Risks Associated With Detoxification, From Animal Models to Human Translational Research

“…Although glutamate levels at the earlier time point were inversely associated with cognitive task performance, improved cognitive function was not related to any changes in glutamate or indeed other MRS markers [creatine, N -acetylaspartate (NAA), choline, and GABA]. Similarly, lower glutamine levels have been found in alcohol-dependent individuals who are still drinking, though breathalyzed negative at the time of the scan, compared with light drinkers (111). An inverse relationship between glutamate, but not glutamine, levels and number of heavy drinking days has been reported in ACC of alcohol-dependent participants but not light drinkers (18).…”