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00925njm 22002777a 4500 dc Weeland, Cees J. author Kasprzak, Selina author de Joode, Niels T. author Abe, Yoshinari author Alonso, Pino author Ameis, Stephanie H. author Anticevic, Alan author Arnold, Paul D. author Balachander, Srinivas author Banaj, Nerisa author Bargalló, Núria author Batistuzzo, Marcelo C. author Benedetti, Francesco author Beucke, Jan C. author Bollettini, Irene author Brecke, Vilde author Brem, Silvia author Cappi, Carolina author Cheng, Yuqi author Cho, Kang Ik K. author Costa, Daniel L. C. author Dallaspezia, Sara author Denys, Damiaan author Eng, Goi Khia author Ferreira, Sónia author Feusner, Jamie D. author Fontaine, Martine author Fouche, Jean-Paul author Grazioplene, Rachael G. author Gruner, Patricia author He, Mengxin author Hirano, Yoshiyuki author Hoexter, Marcelo Q. author Huyser, Chaim author Hu, Hao author Jaspers-Fayer, Fern author Kathmann, Norbert author Kaufmann, Christian author Kim, Minah author Koch, Kathrin author Bin Kwak, Yoo author Kwon, Jun Soo author Lázaro, Luisa author Li, Chiang-shan R. author Lochner, Christine author Marsh, Rachel author Martínez-Zalacaín, Ignacio author Mataix-Cols, David author Menchón Magriñá, José Manuel author Minnuzi, Luciano author Moreira, Pedro Silva author Morgado, Pedro author Nakagawa, Akiko author Nakamae, Takashi author Narayanaswamy, Janardhanan C. author Nurmi, Erika L. author Ortiz, Ana E. author Pariente, Jose C. author Piacentini, John author Picó-Pérez, Maria author Piras, Fabrizio author Piras, Federica author Pittenger, Christopher author Reddy, Y. C. Janardhan author Rodriguez-Manrique, Daniela author Sakai, Yuki author Shimizu, Eiji author Shivakumar, Venkataram author Simpson, Helen Blair author Soreni, Noam author Soriano-Mas, Carles author Sousa, N. author Spalletta, Gianfranco author Stern, Emily R. author Stevens, Michael C. author Stewart, S. Evelyn author Szeszko, Philip R. author Takahashi, Jumpei author Tanamatis, Tais author Tang, Jinsong author Thorsen, Anders Lillevik author Tolin, David author van der Werf, Ysbrand D. author van Marle, Hein author van Wingen, Guido author Vecchio, Daniela author Venkatasubramanian, Ganesan author Walitza, Susanne author Wang, Jicai author Wang, Zhen author Watanabe, Anri author Wolters, Lidewij H. author Xu, Xiufeng author Yun, Je-Yeon author Zhao, Qing author White, Tonya author Thompson, Paul M. author Stein, Dan J. author van den Heuvel, Odile A. author Vriend, Chris author 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 T-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 () 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. Psychiatric disorders Neuroscience The Thalamus and its subnuclei-a gateway to obsessive-compulsive disorder