Resting-State Functional Connectivity Alterations in Obsessive-Compulsive Disorder: Relationships Between Connectivity and Clinical Profiles in the Global OCD Study

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with altered resting-state functional connectivity (FC), but findings are inconsistent and associations with clinical characteristics are unclear. The Global OCD study collected harmonized imaging, demographic, and clinical data across 5 sites and continents, with the aim of identifying consistent OCD-related alterations in FC. METHODS: We included 263 unmedicated adults with OCD (56% naïve to psychotropic medications) and 254 healthy control (HC) participants and estimated FC from resting-state functional magnetic resonance imaging. Between-group differences in and associations of clinical characteristics with FC were analyzed through general linear models adjusted for gender, age, and years of education. We investigated seed-based FC of the amygdala, posterior putamen, nucleus accumbens, and ventral and dorsal caudate nuclei and FC between and within atlas-based subnetworks, global network measures (global efficiency, modularity), and performed network-based statistics (NBS). RESULTS: Seed-based analysis showed weaker FC between the nucleus accumbens and left cerebellum in OCD versus HC groups, while NBS revealed a network of widespread hypoconnectivity spanning 249 regions. In OCD, FC was associated with previous use of selective serotonin/norepinephrine reuptake inhibitors, comorbid major depressive disorder, severity of anxiety, and sexual/religious and contamination symptoms. In particular, anxiety symptoms were linked to widespread stronger FC, while sexual/religious symptoms were linked to stronger sensorimotor FC. CONCLUSIONS: Individuals with OCD showed widespread hypoconnectivity compared with HC participants, with considerable interindividual variation within the OCD group related to previous medication use, comorbid depression, severity of anxiety, and specific OCD symptoms.