The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Cees J. Weeland*, Selina Kasprzak, ENIGMA OCD Working Group, Niels T. de Joode, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Srinivas Balachander, Nerisa Banaj, Nuria Bargallo, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Vilde Brecke, Silvia Brem, Carolina Cappi, Yuqi ChengKang Ik K. Cho, Daniel L.C. Costa, Sara Dallaspezia, Damiaan Denys, Goi Khia Eng, Sónia Ferreira, Jamie D. Feusner, Martine Fontaine, Jean Paul Fouche, Rachael G. Grazioplene, Patricia Gruner, Mengxin He, Yoshiyuki Hirano, Marcelo Q. Hoexter, Chaim Huyser, Hao Hu, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Minah Kim, Kathrin Koch, Yoo Bin Kwak, Jun Soo Kwon, Luisa Lazaro, Chiang shan R. Li, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Jose M. Menchón, Tonya White

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number70
JournalTranslational Psychiatry
Volume12
Issue number1
DOIs
Publication statusPublished - 21 Feb 2022

Bibliographical note

Funding Information:
The ENIGMA Obsessive-Compulsive Disorder Working Group gratefully acknowledges support from the NIH BD2K award U54 EB020403 (PI: P.M. Thompson) and Amsterdam Neuroscience (CIA-2019-03-A to O.A. van den Heuvel, Amsterdam Neuroscience Alliance Project to G.A. van Wingen). Supported by the Japan Society for the Promotion of Science (JSPS; KAKENHI Grants No. 18K15523 to Y. Abe, No. 19K03308 to Y. Hirano and A. Nakagawa, No. 16K04342 to A. Nakagawa); National Institute of Mental Health (NIMH; Grant no. 5R01MH116038 to A. Anticevic, No. R01MH085900 to J.D. Feusner, No. K23 MH115206 to P. Gruner, No. R01MH104648 and No. R21MH101441 to R. Marsh, No. R01MH085900 and No. R01MH081864 to J. O’Neill, No. 1R01MH081864 to J. Piacentini, No. K24 MH121571 to C. Pittenger, No. R01 MH074934, No. R21/R33MH107589 and No. R01MH111794 to E.R. Stern, No. R01 MH074934 to D. Tolin); the Alberta Innovates Translational Health Chair in Child and Youth Mental Health and the Ontario Brain Institute funding P.D. Arnold; Swiss National Science Foundation (Grant No. 320030_130237) and the Hartmann Müller Foundation (Grant No. 1460) to S. Brem; Fundação Faculdade de Medicina (Grant No. 86.768 to D.L.C. Costa); the Japan Agency for Medical Research and Development (AMED Brain/MINDS Beyond program Grant No. JP21dm0307002 to Y. Hirano, No. JP21dm0307008 to Y. Sakai); Michael Smith Foundation for Health Research to F. Jaspers-Fayer; the Deutsche Forschungsgemeinschaft (DFG; to D. Rodriguez-Manrique, Grant No. DFG 815/6-1 to N. Kathmann, No. KO 3744/11-1 to K. Koch); The Basic Science Research Program through the National Research Foundation of Korea (NRF) (Grant no. 2019R1A2B5B03100844 to J.S. Kwon); the Marató TV3 Foundation (Grant No. 01/2010 and No. 091710 to L. Lazaro); the National Research Foundation of South Africa to C. Lochner; the Portuguese Foundation for Science and Technology (Fundação para a Ciência e a Tecnologia; FCT; Project No. UIDB/50026/2020 and No. UIDP/50026/2020 to P. Morgado and N. Sousa); the ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (Grant No. PPBI-POCI-01-0145-FEDER-022122); the Norte Portugal Regional Operational Programme (NORTE 2020; Grant No. NORTE-01-0145-FEDER-000039 to P. Morgado and N. Sousa), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); the FLAD Science Award Mental Health 2021 to P. Morgado and N. Sousa; the Government of India grants from the Department of Science and Technology (Grants No. SR/S0/HS/0016/2011 to Y.C. Janardhan Reddy, and DST INSPIRE faculty grant -IFA12-LSBM-26 to J.C. Narayanaswamy) and from the Department of Biotechnology (Grants No. BT/PR13334/Med/30/259/2009 to Y.C. Janardhan Reddy, and No. BT/06/IYBA/2012 to Dr. Janardhanan C. Narayanaswamy, and Accelerator Program for Discovery in Brain Disorders using Stem cells (ADBS), Grant No. BT/PR17316/MED/31/326/2015 to S. Balachander); the Italian Ministry of Health (Grant No. RC19-20-21 to Fabrizio Piras, No. RC18-19-20-21/A to G. Spalletta); the Wellcome Trust-DBT India Alliance (Grant No. 500236/Z/11/Z to G. Venkatasubramanian, Early Career Fellowship Grant No. IA/CPHE/18/1/503956 to. V. Shivakumar); the Carlos III Health Institute (Grant No. PI16/00889 and No. PI19/01171 to C. Soriano-Mas); the Departament de Salut, Generalitat de Catalunya (Grant No. PERIS SLT006/17/249 to C. Soriano-Mas); the Agència de Gestió d’Ajuts Universitaris i de Recerca (Grant No. 2017 SGR 1262 to C. Soriano-Mas); the International OCD Foundation to P.R. Szeszko; the Helse Vest Health Authority (Grant No. 911754 and No. 911880 to A.L. Thorsen); the Netherlands Organisation for Health Research and Development (ZonMw; VIDI Grant No. 91717306 to O.A. van den Heuvel, TOP Grant No. 91211021 to T. White); the South African Medical Research Council (SAMRC) to D.J. Stein; the Dutch Brain Foundation (Nederlandse Hersenstichting; Grant No. HA-2017-00227 to C. Vriend).

Funding Information:
Alan Anticevic is a shareholder and member of the technology advisory board for RBNC Therapeutics. 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 www.uzh.ch/prof/ssl-dir/interessenbindungen/client/web/ . Her work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diverse EU FP7s, Gesundheitsförderung Schweiz, Bfarm Germany, ZInEP, Hartmann Müller 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.

Publisher Copyright:
© 2022, The Author(s).

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