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Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium

  • the ENIGMA-OCD Working Group

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.
Original languageEnglish
Pages (from-to)204-216
Number of pages13
JournalJournal of Affective Disorders
Volume318
Early online date28 Aug 2022
DOIs
Publication statusPublished - 1 Dec 2022
Externally publishedYes

Funding

The original data collection for this study was funded by Alberta Innovates Translational Health Chair in Child and Youth Mental Health (Arnold); the Ontario Brain Institute (Arnold, Soreni); the German Federal Ministry of Education and Research grant No. BMBF-01GW0724 (Beucke/Kathmann); the NIMH ( K23MH092397 Brennan; K23MH104515 Baker; K23MH115206 Gruner; R01MH107419 , K23MH082176 , R21MH101441 , Marsh; R01MH081864 O’Neill, Piacentini; R01MH085900 O’Neill, Feusner; R21MH093889 Simpson, Marsh; R33MH107589 Stern); NARSAD (Brennan, Fitzgerald, van den Heuvel); Sidney R. Baer, Jr. Foundation (Brennan); EU F97 Project TACTICS grant No. 278948 (Buitelaar); National Natural Science Foundation of China grants No. 81560233 (Cheng) and 81371340 (Wang); Netherlands Organization for Scientific Research grant No. NOW/ZonMW Vidi 917.15.318 (van Wingen); Dana Foundation (Fitzgerald); an International Obsessive-Compulsive Disorder Foundation (IOCDF) Research Award (Gruner); Neuroscience Amsterdam (van den Heuvel); an IPB grant (van den Heuvel); Dutch Organization for Scientific Research (NWO) grants 912-02-050 , 907-00-012 , 940-37-018 , and 916.86.038 (van den Heuvel); Netherlands Organization for Scientific Research grant No. 916.86.036 (van den Heuvel); Netherlands Brain Foundation grant No. (2010(1))-50 (van den Heuvel); JSPS KAKENHI grants No. 22H01090 and 19K03309 (Hirano) and 16K19778 and 18K07608 (Nakamae) 18K15523 (Abe), 21K15749 (Watanabe), and Sakai ( JP22dm0307008 ); Japan Agency for Medical Research and Development AMED Brain/MINDS Beyond Program grant No. JP21dm0307002 (Shimizu); Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo Research Foundation) grants No. 2011/21357-9 , 2018/04654-9 , 2018/21934-5 (Hoexter); Oxford Health Services Research Committee (James); Deutsche Forschungsgemeinschaft (DFG) grant No. KO 3744/11-1 (Koch); the Ministry of Science & ICT grants No. 2020M3E5D9079910 and 2021M3A9E4080784 (Kwon); Marató TV3 Foundation grants No. 01/2010 and 091710 (Lázaro); Carlos III Health Institute grants No. PI040829 (Lázaro), FI17/00294 (Martínez-Zalacaín), Pl16/00950 (Menchón), PI14/00419 and Pl22/00752 (Alonso), PI16/00889 and PI19/01171 (Soriano-Mas); FEDER Funds/ European Regional Development Fund (ERDF) : A Way to Build Europe (Lázaro); Generalitat de Catalunya AGAUR 2017 SGR 881 (Lázaro) and AGAUR 2017 SGR 1247 (Menchón); the Welcome Trust (Mataix-Cols); Pump-Priming Project grant No. 064846 from the South London and Maudsley Trust London UK (Mataix-Cols); Japanese Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research No. (C) 22591262 , (C) 25461732 , and (C) 16K10253 (Nakao); Government of India Department of Science and Technology grant No. SR/S0/HS/0016/2011 (Reddy); Government of India Department of Biotechnology grants No. BT/PR13334/Med/30/259/2009 (Reddy) and BT/06/IYBA/2012 (Narayanaswamy); Wellcome-DBT India Alliance grant No. 500236/Z/11/Z (Venkatasubramanian); DST INSPIRE Faculty Grant No. IFA12-LSBM-26 (Narayanaswamy); Italian Ministry of Health grant No. RC13-14-15-16-17-18A (Spalletta, Fa. Piras, Fe. Piras); South African Medical Research Council Funding (Stein, Lochner); National Research Foundation of South Africa (Stein, Lochner); National Center for Advancing Translational Sciences grants No. UL1TR000067 and KL2TR00069 (Stern); Michael Smith Foundation for Health Research (Jaspers-Fayer, Stewart); Canadian Institutes of Health Research (Stewart), British Columbia Provincial Health Services Authority (Stewart); Swiss National Science Foundation grant No. SNSF 320030_130237 (Walitza); Harmann Müller Foundation grant No. 1460 (Brem); Shanghai Key Laboratory of Psychotic Disorders grant No. 13dz2260500 (Wang), NIH BD2K (Big Data to Knowledge) Award U54 EB020403 (Thompson; Thomopoulos); NIDA grants No. R21DA046029 and R21DA045218 (Ivanov). Dr. Arnold reported holding the Alberta Innovates Translational Health Chair in Child and Youth Mental Health outside the submitted work. Prof. Mataix-Cols receives royalties for contributing articles to UpToDate, Wolters Kluwer Health and fees from Elsevier for editorial tasks (all unrelated to the submitted work). Dr. Narayanaswamy reported Government of India grants DST INSPIRE faculty grant IFA12-LSBM-26 and BT/06/IYBA/2012 outside the submitted work. Dr. Reddy reported Government of India grants SR/S0/HS/0016/2011 and BT/PR13334/Med/30/259/2009 outside the submitted work. Dr. Venkatasubramanian reported Wellcome-DBT India Alliance grant 500236/Z/11/Z outside the submitted work. Dr. Simpson reported Biohaven Research support for a clinical trial and royalties from UpToDate, Inc. and Cambridge University Press outside the submitted work. Dr. Soreni reported support from Lundbeck-IIT outside the submitted work. Dr. Walitza has received in the last 3 years royalties from Thieme Hogrefe, Kohlhammer, Springer, Beltz; Her work was supported in the last 3 years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann Fonds (all unrelated to the submitted work). Dr. Thompson has received a research grant from Biogen, Inc., unrelated to the topic of this paper.

FundersFunder number
South African Medical Research Council
South London and Maudsley Trust London UK
Michael Smith Foundation for Health Research
Netherlands Brain Foundation
Generalitat de Catalunya
Dana Foundation
National Institutes of Health
Provincial Health Services Authority
ZonMW Vidi 917.15.318
Alberta Innovates
Amsterdam Neuroscience
Canadian Institutes of Health Research
National Research Foundation
European Regional Development Fund
Ontario Brain Institute
Biogen, Inc.
International OCD Foundation
National Institute of Mental HealthR33MH107589, K23MH115206, R01MH081864, R01MH107419, K23MH092397, K23MH082176, R21MH093889, R01MH085900, K23MH104515, R21MH101441
National Center for Advancing Translational SciencesUL1TR000067, KL2TR00069
National Alliance for Research on Schizophrenia and Depression278948
Ministero della SaluteRC13-14-15-16-17-18A
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungSNSF 320030_130237
Nederlandse Organisatie voor Wetenschappelijk Onderzoek940-37-018, 912-02-050, 916.86.038, 907-00-012, 916.86.036
Department of Science and Technology, Ministry of Science and Technology, IndiaIFA12-LSBM-26, SR/S0/HS/0016/2011, BT/06/IYBA/2012
Bundesministerium für Bildung und ForschungBMBF-01GW0724
Agència de Gestió d'Ajuts Universitaris i de Recerca2017 SGR 1247
Shanghai Key Laboratory of Psychotic Disorders13dz2260500
Instituto de Salud Carlos IIIFI17/00294, Pl22/00752, PI16/00889, PI14/00419, PI040829, Pl16/00950, PI19/01171
Japan Society for the Promotion of Science19K03309, 18K15523, 18K07608, 22H01090, 16K19778, JP22dm0307008, 21K15749
Wellcome-DBT India Alliance500236/Z/11/Z
Fundació la Marató de TV3091710, 01/2010
Ministry of Education, Culture, Sports, Science and Technology16K10253, 25461732, 22591262
Japan Agency for Medical Research and DevelopmentJP21dm0307002
National Institute on Drug AbuseR21DA045218, R21DA046029
Wellcome Trust064846
National Institute of Biomedical Imaging and BioengineeringU54EB020403
Hartmann Müller-Stiftung für Medizinische Forschung1460
Ministry of Science ICT and Future Planning2021M3A9E4080784, 2020M3E5D9079910
National Natural Science Foundation of China81371340, 81560233
Fundação de Amparo à Pesquisa do Estado de São Paulo2018/04654-9, 2018/21934-5, 2011/21357-9
Government of India Department of BiotechnologyBT/PR13334/Med/30/259/2009
Deutsche ForschungsgemeinschaftKO 3744/11-1

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