White matter microstructure and its relation to clinical features of obsessive–compulsive disorder: findings from the ENIGMA OCD Working Group
Authors: Piras Fabrizio , Piras Federica , Abe Yoshinari , Agarwal Sri Mahavir , Anticevic Alan , Ameis Stephanie , Arnold Paul , Banaj Nerisa , Bargalló Núria , Batistuzzo Marcelo C. , Benedetti Francesco , Beucke Jan-Carl , Boedhoe Premika S. W. , Bollettini Irene , Brem Silvia , Calvo Anna , Cho Kang Ik Kevin , Ciullo Valentina , Dallaspezia Sara , Dickie Erin , Ely Benjamin Adam , Fan Siyan , Fouche Jean-Paul , Gruner Patricia , Gürsel Deniz A. , Hauser Tobias , Hirano Yoshiyuki , Hoexter Marcelo Q. , Iorio Mariangela , James Anthony , Reddy Y. C. Janardhan , Kaufmann Christian , Koch Kathrin , Kochunov Peter , Kwon Jun Soo , Lazaro Luisa , Lochner Christine , Marsh Rachel , Nakagawa Akiko , Nakamae Takashi , Narayanaswamy Janardhanan C. , Sakai Yuki , Shimizu Eiji , Simon Daniela , Simpson Helen Blair , Soreni Noam , Stämpfli Philipp , Stern Emily R. , Szeszko Philip , Takahashi Jumpei , Venkatasubramanian Ganesan , Wang Zhen , Yun Je-Yeon ,   ENIGMA OCD Working Group, Assogna Francesca , Calvo Rosa , Wit Stella J. de , Hough Morgan , Kuno Masaru , Miguel Euripedes C. , Morer Astrid , Pittenger Christopher , Poletti Sara , Smeraldi Enrico , Sato João R. , Tsuchiyagaito Aki , Walitza Susanne , van der Werf Ysbrand D. , Vecchio Daniela , Zarei Mojtaba , Stein Dan J. , Jahanshad Neda , Thompson Paul M. , van den Heuvel Odile A. , Spalletta Gianfranco 
Published: March 2021

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. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed 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, in a cross-sectional case-control magnetic resonance study. 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. 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, 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 controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.