Many of the studies cited within this review analyzed AUD samples diagnosed with other psychiatric comorbidities including various substance use disorders. For example, AUD and tobacco use are highly comorbid. Smoking is associated with region-specific brain volume reductions compared to never smokers, including gray matter volume loss in the PFC, ACC, and other regions overlapping with the neurotoxic effects of alcohol on regional brain volumes (Fritz et al., 2014). Smoking is also associated with reduced cortical thickness of the left medial OFC (Kühn, Schubert, & Gallinat, 2010). Studies have demonstrated that chronic cigarette smoking was associated with larger cortical gray matter volume loss and alterations in cortical thickness in individuals with AUD (Durazzo, Cardenas, Studholme, Weiner, & Meyerhoff, 2007; Durazzo, Mon, Gazdzinski, & Meyerhoff, 2013; Kühn et al., 2010; van Holst, de Ruiter, van den Brink, Veltman, & Goudriaan, 2012). To further complicate the picture, men and women smokers differ with regard to availability of β2-nicotinic acetylcholine receptors (nAChR), to which nicotine binds and activates, and DA D2/3 receptor availability (Cosgrove et al., 2012; Cosgrove et al., 2014; Verplaetse et al., 2018), and it has been shown that alcohol interacts with nAChRs (Larsson & Engel, 2004).
