Prefrontal Glx and GABA concentrations and impulsivity in cigarette smokers and smoking polysubstance users

- Indications of higher dorsal anterior cingulate cortex (dACC) Glx in substance users compared to healthy controls.
- No dACC Glx differences between substance using groups.
- No group differences in dACC gamma-Aminobutyric acid (GABA) concentrations.
- Cocaine users highest in impulsivity, healthy controls lowest, and smokers in between.
- Impulsivity and substance use not correlated with dACC Glx or GABA.

Glutamate and GABA play an important role in substance dependence. However, it remains unclear whether this holds true for different substance use disorders and how this is related to risk-related traits such as impulsivity. We, therefore, compared Glx (as a proxy measure for glutamate) and GABA concentrations in the dorsal anterior cingulate cortex (dACC) of 48 male cigarette smokers, 61 male smoking polysubstance users, and 90 male healthy controls, and investigated the relationship with self-reported impulsivity and substance use. Glx and GABA concentrations were measured using proton Magnetic Resonance Spectroscopy. Impulsivity, smoking, alcohol and cocaine use severity and cannabis use were measured using self-report instruments. Results indicate a trend towards group differences in Glx. Post-hoc analyses showed a difference between smokers and healthy controls (p = 0.04) and a trend towards higher concentrations in smoking polysubstance users and healthy controls (p = 0.09), but no differences between smokers and smoking polysubstance users. dACC GABA concentrations were not significantly different between groups. Smoking polysubstance users were more impulsive than smokers, and both groups were more impulsive than controls. No significant associations were observed between dACC neurotransmitter concentrations and impulsivity and level and severity of smoking, alcohol or cocaine use or the presence of cannabis use. The results indicate that differences in dACC Glx are unrelated to type and level of substance use. No final conclusion can be drawn on the lack of GABA differences due to assessment difficulties. The relationship between dACC neurotransmitter concentrations and cognitive impairments other than self-reported impulsivity should be further investigated.