Gray matter volume alterations following short-term abstinence in alcohol use disorder and their spatial association with neurotransmitter distributions

Abstract Objective To explore gray matter volume (GMV) changes after short-term abstinence in Alcohol Use Disorder (AUD) patients, and their spatial association with normative neurotransmitter density distributions via structural magnetic resonance imaging (sMRI). Methods Forty AUD patients underwent MRI before and after 1-month abstinence. Voxel-based morphometry (VBM) compared GMV changes across brain regions. Exploratory Pearson correlation analysis was performed on GMV changes and clinical assessment indicators, including the Montreal Cognitive Assessment (MoCA), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Spatial correlation analyses using Spearman’s rank correlation were further performed to examine relationships between whole-brain GMV changes and neurotransmitter density distributions, including 5-Hydroxytryptamine (5-HT), Dopamine (DA), γ-Aminobutyric acid (GABA), Norepinephrine (NE), Acetylcholine (ACh), and Glutamate (Glu). Results Compared with pre-abstinence, patients with AUD showed increased GMV in brain regions including the right Rolandic operculum, middle cingulate cortex, middle temporal gyrus, caudate nucleus, precuneus, superior temporal gyrus, middle occipital gyrus, and pulvinar of the thalamus, as well as the left insular cortex, superior temporal gyrus, cuneus, gyrus rectus, middle temporal gyrus, and inferior temporal gyrus. Additionally, an exploratory uncorrected association was observed between GMV changes in the right caudate nucleus and MoCA scores ( r = 0.3841, P = 0.0329), which did not survive false discovery rate (FDR) correction (q = 0.4710). Post-abstinence GMV changes in AUD patients were significantly negatively correlated with the spatial distributions of 5-HT 2 A (rho = -0.7557, P < 0.001, FDR q = 0.0075), GABA A (rho = -0.8290, P < 0.001, FDR q = 0.0075), mGluR5 [mGluR5 (abp_hc28_dubois): rho = -0.6395, P < 0.001, FDR q = 0.0075; mGluR5 (abp_hc73_smart): rho = -0.6757, P < 0.001, FDR q = 0.0075]. Conclusion Patients with AUD exhibit brain structural changes after short-term alcohol abstinence. Spatial patterns of GMV changes were associated with normative PET-derived maps of 5-HT₂A receptors, GABA A receptors, and two independent mGluR5 reference maps. These findings provide preliminary clues for understanding the pathophysiological mechanisms underlying alcohol abstinence-related brain alterations by revealing spatial relationships between GMV changes and neurotransmitter-related molecular architecture.