BACKGROUND At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area and volume in neocortical components of the BRS among non-smoking light drinking controls (Controls), individuals who remained abstinent and those who relapsed after treatment. METHODS Seventy-five treatment-seeking alcohol dependent individuals (abstinent for 7 ± 3 days) and 43 Controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data was obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex, rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol dependent participants were followed over 12-months after baseline study and were classified as Abstainers (no alcohol consumption; n=24) and Relapsers (any alcohol consumption; n=51) at follow-up. RESULTS Relapsers and Abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to Controls. Relapsers had lower total BRS surface area than both Controls and Abstainers, but Abstainers were not significantly different from Controls on any surface area measure. Relapsers demonstrated lower volumes than Controls in the majority of regions, while Abstainers showed lower volumes than Controls in the superior frontal gyrus, insula, amygdala and hippocampus, bilaterally. Relapsers exhibited smaller volumes than Abstainers in the right rostral middle and caudal middle frontal gyri and the lateral orbitofrontal cortex, bilaterally. In Relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. CONCLUSIONS Results suggest Relapsers demonstrated morphological abnormalities in regions involved in the “top down” regulation/modulation of internal drive states, emotions, reward processing and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an AUD. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in AUD. Results from this report are consistent with previous research implicating plastic neurobiological changes the brain reward system in the maintenance of addictive disorders.

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 Glu and GABA 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 4 Tesla. Absolute concentrations of Glu, GABA and those of other 1H 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), and choline- (Cho) and creatine-containing metabolites than LD in the ACC, but 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.

Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.