Resolving heterogeneity in obsessive–compulsive disorder through individualized differential structural covariance network analysis

Abstract Background The high heterogeneity of obsessive–compulsive disorder (OCD) denies attempts of traditional case–control studies to derive neuroimaging biomarkers indicative of precision diagnosis and treatment. Methods To handle the heterogeneity, we uncovered subject-level altered structural covariance by adopting individualized differential structural covariance network (IDSCN) analysis. The IDSCN measures how structural covariance edges in a patient deviated from those in matched healthy controls (HCs) yielding subject-level differential edges. One hundred patients with OCD and 106 HCs were recruited and whose T1-weighted anatomical images were acquired. We obtained individualized differential edges and then clustered patients into subtypes based on these edges. Results Patients presented tremendously low overlapped altered edges while frequently shared altered edges within subcortical–cerebellum network. Two robust neuroanatomical subtypes were identified. Subtype 1 presented distributed altered edges while subtype 2 presented decreased edges between default mode network and motor network compared with HCs. Altered edges in subtype 1 predicted the total Yale-Brown Obsessive Compulsive Scale score while that in subtype 2 could not. Conclusions We depict individualized structural covariance aberrance and identify that altered connections within subcortical–cerebellum network are shared by most patients with OCD. These 2 subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of OCD.