Glutamate, GABA, and other cortical metabolite concentrations during early abstinence from alcohol and their associations with neurocognitive changes

Abstract

Background: Little is known about the effects of alcohol dependence on cortical concentrations of glutamate (Glu) or gamma aminobutyric acid (GABA). We used proton magnetic resonance spectroscopy (MRS) to study cross-sectionally and longitudinally the concentrations of these in alcohol dependent individuals (ALC) during early abstinence from alcohol.

Methods: Twenty ALC were studied at about one week of abstinence from alcohol (baseline) and 36 ALC at five weeks of abstinence and compared to 16 light/non-drinking controls (LD). Eleven ALC were studied twice during abstinence. Participants underwent clinical interviewing, blood work, neuropsychological testing, structural imaging and single-volume proton MRS at 4Tesla. Absolute concentrations of Glu, GABA and those of other (1)H MRS-detectable metabolites were measured in the anterior cingulate (ACC), parieto-occipital cortex (POC) and dorso-lateral prefrontal cortex (DLPFC). Relationships of metabolite levels to drinking severity and neurocognition were also assessed.

Results: ALC at baseline had lower concentrations of Glu, N-acetylaspartate (NAA), choline- (Cho) and creatine-containing metabolites (Cr) than LD in the ACC, but had normal GABA and myo-inositol (mI) levels. At five weeks of abstinence, metabolite concentrations were not significantly different between groups. Between one and five weeks of abstinence, Glu, NAA and Cho levels in the ACC increased significantly. Higher cortical mI concentrations in ALC related to worse neurocognitive outcome.

Conclusion: These MRS data suggest compromised and regionally specific bioenergetics/metabolism in one-week-abstinent ALC that largely normalizes over four weeks of sustained abstinence. The correlation between mI levels and neurocognition affirms the functional relevance of this putative astrocyte marker.

Conflict of interest statement

Conflict of Interest

None of the authors has any conflict of interest in this study

Published by Elsevier Ireland Ltd.

Figures

Figure 1

T2-weighted images showing ACC (left), right DLPFC (middle) and POC (right) volumes-of-interest

Figure 2

STEAM sequence spectrum (TR/TE/TM = 2000/12/20 ms) with main resonances for NAA, Glu, Cr, Cho and mI

Figure 3

J-edited spectrum of GABA and Glx (TR/TE = 2000/71 ms)

Figure 4

Plots of ACC Glu/H20 in 11 ALC at TP1 and TP2. The gray region indicates mean ± standard deviation of Glu/H20 in LD. Glu increases in the 11 ALC were significant (p = 0.008), even when removing the individual with the greatest change.

Figure 5

Plots of ACC NAA concentration against ACC Glu concentration. a: plot for TP1, b: plot for TP2.