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 five sites and continents, with the aim of identifying consistent OCD-related alterations in FC. Methods We included 263 unmedicated adults with OCD and 254 healthy controls (HC) 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 sex, age and years of education. We investigated seed-based FC of the amygdala, posterior putamen, nucleus accumbens, ventral and dorsal caudate nucleus, 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, 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 show widespread hypoconnectivity compared to HC, with considerable interindividual variation within OCD related to previous medication use, comorbid depression, severity of anxiety, and specific OCD symptoms. General hypoconnectivity in OCD may be a good target for interventions modulating brain circuit connectivity, including transcranial magnetic stimulation.