GABA concentrations in the anterior cingulate and dorsolateral prefrontal cortices: Associations with chronic cigarette smoking, neurocognition, and decision making

Chronic cigarette smoking is associated with regional metabolite abnormalities in choline-containing compounds, creatine-containing compounds, glutamate, and N-acetylaspartate. The effects of cigarette smoking on anterior frontal cortical gamma-aminobutyric acid (GABA) concentration is unknown. This study compared chronic smokers (n=33) and non-smokers (n=31) on anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC) GABA+ (the sum of GABA and co-edited macromolecules) concentrations and associations of GABA+ levels in these regions with neurocognition in seven different domains of functioning, decision-making and impulsivity measures. Smokers had significantly lower right DLPFC GABA+ concentration than non-smokers, but groups were equivalent on ACC GABA+ level. Across groups, greater number of days since end of menstrual cycle were related to higher GABA+ level in the ACC, but not right DLPFC GABA+ concentration. In exploratory correlation analyses, higher ACC and right DLPFC GABA+ levels were associated with faster processing speed and better auditory-verbal memory, respectively in the combined group of smokers and non-smokers; in smokers only, higher ACC GABA+ was related to better decision-making and auditory-verbal learning. This study contributes additional novel data on the adverse effects of chronic cigarette smoking on the adult human brain and demonstrated ACC and DLPFC GABA+ concentrations were associated with neurocognition and decision-making/impulsivity in active cigarette smokers. Longitudinal studies on the effects of smoking cessation on regional brain GABA levels, with a greater number of female participants, are required to determine if the observed metabolite abnormalities are persistent or normalize with smoking cessation.