Cortical and subcortical structural alterations in obsessive-compulsive disorder: relationships between morphology and clinical profiles in the Global OCD study

BackgroundThe Global OCD consortium investigated cortical and subcortical alterations in obsessive-compulsive disorder (OCD) using T1-weighted MRI, focusing on the relationship between brain morphology and clinical phenotypes, illness duration, comorbidity and medication history. MethodsThis preregistered study included 266 medication-free adults with OCD and 254 healthy controls. We analyzed cortical thickness, surface area, and (sub)cortical and cerebellar volumes using FreeSurfer ROI metrics and voxel-based morphometry (VBM). All analyses included age, sex, IQ, and site as covariates. ResultsWe found no significant differences in cortical thickness, surface area, or subcortical volumes between OCD and HC groups. OCD severity correlated negatively with surface area in the left lateral orbitofrontal cortex (OFC) (p(FDR)=0.008), right medial OFC (p(FDR)=0.009), and right insula (p(FDR)=0.045), findings that were supported by VBM analyses. Analyses related to obsessive-compulsive (OC) symptom dimensionality showed a negative correlation between harm and aggression scores and surface area in the right medial OFC (p(FDR)=0.030), while sexual and religious scores positively correlated with hippocampal volume (p(FDR)=0.017). Compared to those without, OCD cases with comorbid depressive disorders showed a smaller surface area of the inferior parietal cortex (p(FDR)=0.048) and bilateral middle temporal cortices (R:p(FDR)=0.048; L:p(FDR)=0.049). No associations were found for illness duration, age of onset, or past medication use. ConclusionsThis study identified structural changes associated with illness severity, OC symptom dimensionality, and comorbidities. Our results emphasize the role of the OFC and insula in OCD and suggest comorbidity-specific alterations. The absence of case-control differences may stem from the inclusion of medication-free individuals and clinical heterogeneity within the OCD group.