Metabolite levels in the brain reward pathway discriminate those who remain abstinent from those who resume hazardous alcohol consumption after treatment for alcohol dependence

Abstract

Objective: This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence.

Method: Fifty-one treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, choline-containing compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classified as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest.

Results: Resumers demonstrated significantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest.

Conclusions: The significantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite differences between abstainers and light-drinking nonsmoking controls suggests premorbid factors potentially contributed to the baseline brain metabolite abnormalities observed in resumers.

Figure 1

Representative example of proton magnetic resonance spectroscopic imaging multislice spatial positioning on sagittal T1-weighted magnetic resonance imaging