Brain structural covariance networks in obsessive-compulsive disorder: A graph analysis from the ENIGMA consortium

Abstract

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect commontrajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsivedisorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scansacquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCDWorking Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to thesimilarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Globalnetworks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency),and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networkswas undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measureswere integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the networkdensity range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering(P<0.0001), lower modularity (P<0.0001), and lower small-worldness (P = 0.017). Detection of community membershipemphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed)centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicativeof altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated withOCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of thisstudy, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariancenetworks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometryin OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularlyin cingulate and orbitofrontal regions.