White Matter Microstructure and its Relation to Clinical Features of Obsessive-Compulsive Disorder: Findings from the ENIGMA OCD Working Group

ABSTRACT Importance Microstructural alterations in cortico-subcortical connections are thought to be present in Obsessive-Compulsive Disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Objective To investigate microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. Design, Setting, and Participants In this cross-sectional case-control magnetic resonance study, we investigated diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA-OCD Working Group. Main Outcomes and Measures We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d ) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Results Adult OCD patients showed significant FA reduction in the sagittal stratum ( d =-0.21, z=-3.21, p=0.001) and posterior thalamic radiation ( d =-0.26, z =-4.57, p<0.0001). In the sagittal stratum only, lower FA was associated with a younger age of onset (z=2.71, p=0.006), longer duration of illness (z=-2.086, p=0.036) and a higher percentage of medicated patients in the cohorts studied (z=-1.98, p=0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to matched controls. Conclusions and Relevance Microstructural alterations in projection and association fibers to posterior brain regions were found in adult OCD, and related to disease course and medication status. Such results are relevant to models positing deficits in connectivity as a crucial mechanism in OCD. KEY POINTS Question Do patients with Obsessive-Compulsive Disorder (OCD) show white matter microstructural alterations, and are these alterations related to clinical features? Findings Data from 19 sites of the ENIGMA-OCD Consortium were included, involving 700 adult patients and 645 adult controls, 174 pediatric patients and 144 pediatric controls. Diffusion tensor imaging data were meta-analyzed using a harmonized data processing and analysis protocol. Adult, but not pediatric, patients showed alterations in the sagittal stratum and posterior thalamic radiation; sagittal stratum differences were associated with clinical features. Meaning Microstructural abnormalities found in adult but not in the pediatric cohort, are related to illness duration and medication status.