Cigarette smoking, history of major depression and PTSD diagnosis are associated with metabolite levels in the left dorsolateral prefrontal cortex in those in treatment for alcohol use disorder

Drug and alcohol dependence
 |
Timothy C Durazzo, Riley E Carolan, Lauren H Beauregard, Meng Gu, Claudia B Padula

Drug Alcohol Depend. 2026 May 13;285:113194. doi: 10.1016/j.drugalcdep.2026.113194. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the known systemic health risks associated with cigarette smoking, research investigating the neurobiological consequences of smoking in those with alcohol use disorder (AUD) is minimal. This study compared metabolite levels in the left dorsolateral prefrontal cortex (DLPFC) in non-cigarette smoking individuals, former cigarette smoking individuals and active cigarette smoking individuals who were Veterans in residential treatment for AUD.

METHODS: Water scaled concentrations were obtained for N-acetylaspartate (NAA), choline-containing compounds (Cho) creatine-containing compounds (Cr), gamma-aminobutyric acid (GABA) and glutamate (Glu). Actively smoking AUD (AsAUD, n = 46) used cigarettes daily; former smoking AUD (FsAUD, n = 41) were predominately daily cigarette consumers prior to study, with variable lengths of cessation; non-smoking AUD (NsAUD, n = 32) never used cigarettes or seldomly smoked during lifetime. Given the high prevalence of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) in Veterans with AUD, these conditions served as factors in all analyses.

RESULTS: AsAUD had lower NAA, Cho and Cr than NsAUD and lower Cr than FsAUD; there were no metabolite level differences between FsAUD and NsAUD. Individuals with no history of MDD showed lower NAA and Cho levels than those with current MDD and past MDD; current MDD and past MDD were not different on any metabolite concentration. Individuals with a current PTSD diagnosis demonstrated lower Cr level than those with no PTSD diagnosis.

CONCLUSIONS: Results suggest that smoking, MDD and PTSD history are associated with left DLPFC brain metabolite concentrations during early AUD recovery. These novel findings also support the clinical practice of offering smoking cessation resources concurrent with AUD treatment.

PMID:42150346 | DOI:10.1016/j.drugalcdep.2026.113194