Symptom-Based Profiling and Multimodal Neuroimaging of a Large Preteenage Population Identifies Distinct Obsessive-Compulsive Disorder–like Subtypes With Neurocognitive Differences

Background: Obsessive-compulsive disorder (OCD) is characterized by both internalizing (anxiety) and externalizing (compulsivity) symptoms. Currently, little is known about their interrelationships and their relative contributions to disease heterogeneity. Our goal is to resolve affective and cognitive symptom heterogeneity related to internalized and externalized symptom dimensions by determining subtypes of children with OCD symptoms, and to identify any corresponding neural differences. Methods: A total of 1269 children with OCD symptoms screened using the Child Behavior Checklist Obsessive-Compulsive Symptom scale and 3987 matched control subjects were obtained from the Adolescent Brain Cognitive Development (ABCD) Study. Consensus hierarchical clustering was used to cluster children with OCD symptoms into distinct subtypes. Ten neurocognitive task scores and 20 Child Behavior Checklist syndrome scales were used to characterize cognitive/behavioral differences. Gray matter volume, fractional anisotropy of major white matter fiber tracts, and functional connectivity among networks were used in case-control studies. Results: We identified two subgroups with contrasting patterns in internalized and externalized dimensions. Group 1 showed compulsive thoughts and repeated acts but relatively low anxiety symptoms, whereas group 2 exhibited higher anxiety and perfectionism and relatively low repetitive behavior. Only group 1 had significant cognitive impairments and gray matter volume reductions in the bilateral inferior parietal lobe, precentral gyrus, and precuneus gyrus, and had white matter tract fractional anisotropy reductions in the corticostriatal fasciculus. Conclusions: Children with OCD symptoms are heterogeneous at the level of symptom clustering and its underlying neural basis. Two subgroups represent distinct patterns of externalizing and internalizing symptoms, suggesting that anxiety is not its major predisposing factor. These results may have implications for the nosology and treatment of preteenage OCD.