Perturbation of the glutamate-glutamine system in XXXX and remission.

@entity1 @entity988 @entity7748 @entity16223
As acute ethanol exposure inhibits N-methyl-D-aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu-Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with @entity16223 . Glu and Gln levels were compared in groups of 17 healthy controls and in 13 @entity1 with @entity988 . Within the alcohol-dependent group, seven @entity1 had current @entity16223 ( @entity16223 ), and six had @entity16223 in remission for at least 1 year ( @entity16223 -R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy ((1)H- @entity7748 ) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the (1)H- @entity7748 voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all @entity1 to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the @entity16223 and @entity16223 -R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the (1)H- @entity7748 voxel. Neurometabolite concentrations did not differ between @entity16223 and @entity16223 -R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined @entity16223 and @entity16223 -R groups might indicate a perturbation of the Glu-Gln cycle in @entity16223 . The absence of differences in mean Glu and Gln between the @entity16223 and @entity16223 -R groups suggests that altered Glu-Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.
