Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen’s d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen’s d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Background: Pediatric obsessive-compulsive disorder (OCD) is a common, debilitating illness. When childhood OCD symptom onset is described as acute and severe, diagnostic criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) should be considered. However, the frequency and differentiating features of these putative syndromes within pediatric OCD remain poorly understood. Objectives: To determine the prevalence and characteristics of those meeting PANDAS and/or PANS criteria within pediatric OCD, as determined by parent report and clinician interview. Methods: Consecutive youth presenting to a subspecialty pediatric OCD clinic were rigorously assessed through the Anxiety Disorders Interview Schedule for DSM-IV, the Children's Yale–Brown Obsessive-Compulsive Scale, and through self- and parent-report measures, including a medical questionnaire. Strict diagnostic criteria for PANDAS and PANS were applied to determine prevalence rates, and comparative analyses were performed between subgroups. Results: Among 136 youth with a lifetime OCD diagnosis, 5% (n = 7; 95% adjusted Wald interval: 1%–10%) met proposed criteria for PANDAS and/or PANS, of whom two met PANDAS criteria, four met PANS criteria, and one met criteria for both. Those in the PANDAS/PANS subgroup were more likely to have autoimmune illness, less likely to report symmetry factor symptoms, and had greater OCD-related family impairment during their worst OCD episode. Conclusion: A small yet significant percentage of pediatric OCD outpatients met criteria for PANDAS and/or PANS, justifying routine screening and attention to related characteristics during assessment and management. Longitudinal studies of these putative subtypes are warranted.