Common abnormality of gray matter integrity in substance use disorder and obsessive-compulsive disorder: A comparative voxel-based meta-analysis

Abstract

Aim: To determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case-control studies examining gray matter alterations in substance use disorders (SUD) and obsessive-compulsive disorder (OCD). Design: Pre-registered voxel-based meta-analysis of grey matter volume (GMV) changes through seed-based d Mapping (SDM), follow-up functional, and network-level characterization of the identified transdiagnostic regions by means of co-activation and Granger Causality (GCA) analysis. Participants: Literature search resulted in 31 original VBM studies comparing SUD (n=1191, mean-age=40.03, SD=10.87) and 30 original studies comparing OCD (n=1293, mean-age=29.18, SD=10.34) patients with healthy controls (SUD: n=1585, mean-age=42.63, SD=14.27, OCD: n=1374, mean-age=28.97, SD=9.96). Measurements: Voxel-based meta-analysis within the individual disorders as well as conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta-analytic coordinates and signed brain volumetric maps determining directed (reduced or increased) brain volumetric alterations between the disorder groups and controls served as the primary outcome. Meta-analytic results employed statistical significance thresholding (FWE<0.05). Findings: Separate meta-analysis demonstrated that SUD (cocaine, alcohol, and nicotine) as well as OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular regions. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology. Conclusions: Findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.