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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<jats:sub>1<\/jats:sub>-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 <jats:italic>ThalamicNuclei<\/jats:italic> 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 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/osf.io\/73dvy\">https:\/\/osf.io\/73dvy<\/jats:ext-link>) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (&lt;12 years) had larger lateral (<jats:italic>d<\/jats:italic>\u2009=\u20090.46), pulvinar (<jats:italic>d<\/jats:italic>\u2009=\u20090.33<jats:italic>)<\/jats:italic>, ventral (<jats:italic>d<\/jats:italic>\u2009=\u20090.35) and whole thalamus (<jats:italic>d<\/jats:italic>\u2009=\u20090.40) volumes at unadjusted <jats:italic>p<\/jats:italic>-values &lt;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 (<jats:italic>d<\/jats:italic>\u2009=\u2009<jats:italic>\u2212<\/jats:italic>0.15 to \u22120.07) 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.<\/jats:p>","DOI":"10.1038\/s41398-022-01823-2","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T18:10:51Z","timestamp":1645467051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["The thalamus and its subnuclei\u2014a gateway to obsessive-compulsive disorder"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-3769","authenticated-orcid":false,"given":"Cees J.","family":"Weeland","sequence":"first","affiliation":[]},{"given":"Selina","family":"Kasprzak","sequence":"additional","affiliation":[]},{"given":"Niels T.","family":"de Joode","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-0801","authenticated-orcid":false,"given":"Yoshinari","family":"Abe","sequence":"additional","affiliation":[]},{"given":"Pino","family":"Alonso","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7282-6077","authenticated-orcid":false,"given":"Stephanie H.","family":"Ameis","sequence":"additional","affiliation":[]},{"given":"Alan","family":"Anticevic","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-4624","authenticated-orcid":false,"given":"Paul D.","family":"Arnold","sequence":"additional","affiliation":[]},{"given":"Srinivas","family":"Balachander","sequence":"additional","affiliation":[]},{"given":"Nerisa","family":"Banaj","sequence":"additional","affiliation":[]},{"given":"Nuria","family":"Bargallo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1347-8241","authenticated-orcid":false,"given":"Marcelo C.","family":"Batistuzzo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-856X","authenticated-orcid":false,"given":"Francesco","family":"Benedetti","sequence":"additional","affiliation":[]},{"given":"Jan C.","family":"Beucke","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3666-3538","authenticated-orcid":false,"given":"Irene","family":"Bollettini","sequence":"additional","affiliation":[]},{"given":"Vilde","family":"Brecke","sequence":"additional","affiliation":[]},{"given":"Silvia","family":"Brem","sequence":"additional","affiliation":[]},{"given":"Carolina","family":"Cappi","sequence":"additional","affiliation":[]},{"given":"Yuqi","family":"Cheng","sequence":"additional","affiliation":[]},{"given":"Kang Ik K.","family":"Cho","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-8567","authenticated-orcid":false,"given":"Daniel L. 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Jamie D. Feusner is affiliated with NOCD, LLC; Prof. Mataix-Cols receives personal fees from UpToDate, Inc and Elsevier, both outside the current work; Pedro Morgado has received in the past 3 years grants, CME-related honoraria, or consulting fees from Angelini, AstraZeneca, Bial Foundation, Biogen, DGS-Portugal, FCT, FLAD, Janssen-Cilag, Gulbenkian Foundation, Lundbeck, Springer Healthcare, Tecnimede and 2CA-Braga; Erika L. Nurmi served on the Scientific Advisory Board of Myriad Genetics and Medical Advisory Board of Tourette Association of America and Teva Pharmaceuticals; Christopher Pittenger is a consultant for Biohaven, CH-TAC, Lundbeck (not relevant to this work); in the last 3 years, Dr. Simpson has received research support from Biohaven for a multi-site clinical trial, royalties from Cambridge University Press and UpToDate, Inc, and a stipend from the American Medical Association for serving as Associate Editor of JAMA-Psychiatry; Susanne Walitza received no funds of Industry Outside professional activities and interests are declared under the link of the University of Zurich . Her work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diverse EU FP7s, Gesundheitsf\u00f6rderung Schweiz, Bfarm Germany, ZInEP, Hartmann M\u00fcller Stiftung, Olga Mayenfisch, Gertrud Thalmann, Vontobel, Unicentia, Erika Schwarz Fonds. Paul M. Thompson received partial research support from Biogen, Inc., for research unrelated to this manuscript; Chris Vriend is listed as an inventor on a patent licensed to General Electronic (WO2018115148A1). Odile A. van den Heuvel received a consultation honorarium from Lundbeck. All other authors from the ENIGMA OCD working group have no conflicts of interest related to this study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}