The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder
Authors: Weeland Cees J. , Kasprzak Selina , de Joode Niels T. , Abe Yoshinari , Alonso Pino , Ameis Stephanie H. , Anticevic Alan , Arnold Paul D. , Balachander Srinivas , Banaj Nerisa , Bargallo Nuria , Batistuzzo Marcelo C. , Benedetti Francesco , Beucke Jan C. , Bollettini Irene , Brecke Vilde , Brem Silvia , Cappi Carolina , Cheng Yuqi , Cho Kang Ik K. , Costa Daniel L. C. , Dallaspezia Sara , Denys Damiaan , Eng Goi Khia , Ferreira Sónia , Feusner Jamie D. , Fontaine Martine , Fouche Jean-Paul , Grazioplene Rachael G. , Gruner Patricia , He Mengxin , Hirano Yoshiyuki , Hoexter Marcelo Q. , Huyser Chaim , Hu Hao , Jaspers-Fayer Fern , Kathmann Norbert , Kaufmann Christian , Kim Minah , Koch Kathrin , Bin Kwak Yoo , Kwon Jun Soo , Lazaro Luisa , Li Chiang-shan R. , Lochner Christine , Marsh Rachel , Martínez-Zalacaín Ignacio , Mataix-Cols David , Menchón Jose M. , Minnuzi Luciano , Moreira Pedro Silva , Morgado Pedro , Nakagawa Akiko , Nakamae Takashi , Narayanaswamy Janardhanan C. , Nurmi Erika L. , Ortiz Ana E. , Pariente Jose C. , Piacentini John , Picó-Pérez Maria , Piras Fabrizio , Piras Federica , Pittenger Christopher , Reddy Y. C. Janardhan , Rodriguez-Manrique Daniela , Sakai Yuki , Shimizu Eiji , Shivakumar Venkataram , Simpson Helen Blair , Soreni Noam , Soriano-Mas Carles , Sousa Nuno , Spalletta Gianfranco , Stern Emily R. , Stevens Michael C. , Stewart S. Evelyn , Szeszko Philip R. , Takahashi Jumpei , Tanamatis Tais , Tang Jinsong , Thorsen Anders Lillevik , Tolin David , van der Werf Ysbrand D. , van Marle Hein , van Wingen Guido A. , Vecchio Daniela , Venkatasubramanian G. , Walitza Susanne , Wang Jicai , Wang Zhen , Watanabe Anri , Wolters Lidewij H. , Xu Xiufeng , Yun Je-Yeon , Zhao Qing ,   ENIGMA OCD Working Group, White Tonya , Thompson Paul M. , Stein Dan J. , van den Heuvel Odile A. , Vriend Chris 
Published: February 2022

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = −0.15 to −0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.