Distinct structural abnormalities in obsessive-compulsive and alcohol use disorders

Abstract Background Understanding how compulsive behaviors emerge across psychiatric conditions requires mapping disorder-specific neural and potential structural mechanisms. Although Obsessive-Compulsive Disorder (OCD) and Alcohol Use Disorder (AUD) share behavioral features and involve overlapping control- and habit-learning- related circuits, these behaviors may arise from distinct circuit-level pathophysiology. Methods Here we compared gray matter (GM) and white matter (WM) volumes across individuals with AUD, OCD, and healthy controls (HC) using a consistently acquired and uniformly processed dataset. Eighty-six non-comorbid participants (21 OCD, 9 males; 43 AUD, 27 males; and 22 HC, 14 males) underwent high-resolution T1-weighted MRI and region-based morphometry to examine group differences across 126 GM and 68 WM regions of interest. Results Relative to HC, the OCD and AUD groups demonstrated significant opposing patterns of GM alterations across 11 fronto-striatal, limbic, and brainstem regions, with increased volumes in OCD and decreased volumes in AUD. These volumetric differences were not correlated with severity of clinical symptoms recorded in these patients. WM analyses revealed no significant group differences. Conclusions Our study suggests that the shared behavioral features of OCD and AUD are supported by distinct neuroanatomical mechanisms rather than a common structural substrate. Although both disorders involve overlapping circuits, the structural alterations within these networks diverge in their expression, consistent with disorder-specific pathophysiological processes. By applying region-based morphometry in a non-comorbid cohort, the present study identifies disorder-specific volumetric neural signatures in OCD and AUD, refining transdiagnostic models and underscoring the potential clinical utility of neuroimaging markers for differential diagnosis and circuit-informed intervention strategies. Clinical trial registration ClinicalTrials.gov, NCT02691390 and NCT07116785.