Abstract
No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
Original language | English |
---|---|
Article number | 342 |
Journal | Translational Psychiatry |
Volume | 10 |
Issue number | 1 |
DOIs | |
State | Published - 1 Dec 2020 |
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In: Translational Psychiatry, Vol. 10, No. 1, 342, 01.12.2020.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium
T2 - medication matters
AU - ENIGMA-OCD Working Group
AU - Bruin, Willem B.
AU - Taylor, Luke
AU - Thomas, Rajat M.
AU - Shock, Jonathan P.
AU - Zhutovsky, Paul
AU - Abe, Yoshinari
AU - Alonso, Pino
AU - Ameis, Stephanie H.
AU - Anticevic, Alan
AU - Arnold, Paul D.
AU - Assogna, Francesca
AU - Benedetti, Francesco
AU - Beucke, Jan C.
AU - Boedhoe, Premika S.W.
AU - Bollettini, Irene
AU - Bose, Anushree
AU - Brem, Silvia
AU - Brennan, Brian P.
AU - Buitelaar, Jan K.
AU - Calvo, Rosa
AU - Cheng, Yuqi
AU - Cho, Kang Ik K.
AU - Dallaspezia, Sara
AU - Denys, Damiaan
AU - Ely, Benjamin A.
AU - Feusner, Jamie D.
AU - Fitzgerald, Kate D.
AU - Fouche, Jean Paul
AU - Fridgeirsson, Egill A.
AU - Gruner, Patricia
AU - Gürsel, Deniz A.
AU - Hauser, Tobias U.
AU - Hirano, Yoshiyuki
AU - Hoexter, Marcelo Q.
AU - Hu, Hao
AU - Huyser, Chaim
AU - Ivanov, Iliyan
AU - James, Anthony
AU - Jaspers-Fayer, Fern
AU - Kathmann, Norbert
AU - Kaufmann, Christian
AU - Koch, Kathrin
AU - Kuno, Masaru
AU - Kvale, Gerd
AU - Kwon, Jun Soo
AU - Liu, Yanni
AU - Lochner, Christine
AU - Szeszko, Philip R.
AU - Figee, Martijn
AU - Stein, Dan J.
N1 - Funding Information: Dr. Baker has received research support from the National Institute of Mental Health (NIMH) and Valera Health. Dr. Brennan has received consulting fees from Rugen Therapeutics and Nobilis Therapeutics and research grant support from Eli Lilly, Transcept Pharmaceuticals, and Biohaven Pharmaceuticals. Dr. Walitza has received lecture honoraria Opopharma in the last 3 years. Her work was supported in the last 3 years by the Swiss National Science Foundation (SNF), diverse EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, Zinep, Hartmann Müller Stiftung, Olga Mayenfisch. Dr. Dan J. Stein has received research grants and/or consultancy honoraria from Lundbeck and Sun in the past 3 years. Dr. Paul M. Thompson has received research grant support from Biogen, Inc., for research unrelated to the topic of this manuscript. Dr. Ivanov has received honoraria from Lundbeck as a member of the Data Safety Monitoring Committee and research grants from the National Institute on Drug Abuse in the last 3 years. Dr. Pittenger has received research support and/or honoraria for consultation from Biohaven Pharmaceuticals, Blackthorn Therapeutics, Abide Therapeutics, and Brainsway, and royalties or honoraria from Oxford University Press and Elsevier in the past 3 years. Dr. Feusner has received an honorarium from Pfizer and consultation fees from NOCD, Inc. Dr. Piacentini has received research support from Pfizer Pharmaceuticals for research unrelated to the topic of this manuscript. Dr. Soreni has received support for Investigator Initiated Clinical Trial from Lundbeck LLC unrelated to the topic of this study. Dr. Buitelaar has been in the past 3 years a consultant to/member of advisory board of/and/or speaker for Shire, Roche, Medice, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. Dr. Mataix-Cols receives royalties for contributing articles to UpToDate (Wolters Kluwer Health), and for editorial work from Elsevier, all unrelated to the current work. In the last three years, Dr. Simpson has received research support for an industry-sponsored clinical trial from Biohaven Pharmaceuticals, royalties from UpToDate, Inc, and a stipend from JAMA Psychiatry for her role as Associate Editor. Dr. Tolin has received research support from Biohaven Pharmaceuticals. All other individually-named authors in-and outside of the ENIGMA-OCD working group reported no biomedical financial interests or potential conflicts of interest. Funding Information: The ENIGMA-Obsessive Compulsive Disorder Working-Group gratefully acknowledges support from the NIH BD2K (Big Data to Knowledge) award U54 EB020403 (PI: Dr. Thompson) and Neuroscience Amsterdam, and an IPB grant to Dr. Schmaal and Dr. van den Heuvel. Supported by the Japan Society for the Promotion of Science (JSPS; KAKENHI Grants No. 18K15523 to Dr. Abe, No. 16K19778, No. 18K07608 to Dr. Nakamae, No. 16K04344, 19K03309 to Dr. Hirano, and No. 26461762 to Dr. Nakagawa); the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo Research Foundation; Grant No. 2011/21357-9; 2018/04654-9 and 2018/21934-5); the EU FP7 project TACTICS (Grant No. 278948 to Dr. Buitelaar); the National Natural Science Foundation of China (No. 81560233 to Dr. Cheng); the International Obsessive-Compulsive Disorder Foundation (IOCDF) Research Award to Dr. Gruner; the Dutch Organization for Scientific Research (NWO) (grants 912-02-050, 907-00-012, 940-37-018, and 916.86.038); the Netherlands Society for Scientific Research (NWO-ZonMw VENI grant 916.86.036 to Dr. van den Heuvel; NWO-ZonMw AGIKO stipend 920-03-542 to Dr. de Vries), a NARSAD Young Investigator Award to Dr. van den Heuvel, and the Netherlands Brain Foundation (2010(1)-50 to Dr. van den Heuvel); the Federal Ministry of Education and Research of Germany (No. BMBF-01GW0724 to Dr. Kathmann); the Alberta Innovates Translational Health Chair in Child and Youth Mental Health and funding from the Ontario Brain Institute to Dr. Arnold; the Deutsche Forschungsgemeinschaft (DFG; Grant No. KO 3744/7-1 to Dr. Koch); the Helse Vest Health Authority (No. 911754, 911880 to Dr. Kvale) and the Norwegian Research Council (No. HELSEFORSK 243675 to Dr. Kvale); the Wellcome Trust and a pump priming grant from the South London and Maudsley Trust, London, UK (Project Grant No. 064846 to Dr. Mataix-Cols); the Generalitat de Catalunya (AGAUR 2017 SGR 1247 to Dr. Menchón); the PhD-iHES program (FCT fellowship Grant No. PDE/BDE/113601/2015 to Dr. Moreira); the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research (C) 22591262, 25461732, 16K10253 to Dr. Nakao); the Italian Ministry of Health (No. RC13-14-15-16-17-18A to Dr. Spalletta, Dr. Piras Fabrizio, Dr. Piras Federica); the National Center for Advancing Translational Sciences (Grants No. UL1TR000067/KL2TR00069 to Dr. Stern); the SA MRC funding and the National Research Foundation of South Africa to Dr. Stein and Dr. Lochner; the Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, and British Columbia Provincial Health Services Authority funding Dr. Stewart; the Netherlands Organization for Scientific Research (NWO/ZonMW Vidi 917.15.318 to Dr. van Wingen); the Wellcome-DBT India Alliance (Grant No. 500236/Z/11/Z to Dr. Venkatasubramanian); the National Natural Science Foundation of China (No. 81371340) and the Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500) to Dr. Wang; the Government of India grants from the Department of Science and Technology (Grants No. SR/S0/HS/0016/2011 to Prof. Y.C. Janardhan Reddy, and DST INSPIRE faculty grant-IFA12-LSBM-26 to Dr. Janardhanan C. Narayanaswamy) and from the Department of Biotechnology (Grants No. BT/PR13334/Med/30/259/2009 to Prof. Y.C. Janardhan Reddy, and No. BT/06/IYBA/2012 to Dr. Janardhanan C. Narayanaswamy); the Dana Foundation and NARSAD to Dr. Fitzgerald; the NIMH (Grants No. R01 MH107419 and No. K23MH082176 to Dr. Fitzgerald, Grant No. R21MH101441 to Dr. Marsh, Grant No. R21MH093889 to Drs. Marsh and Simpson, Grant No. K23-MH104515 to Dr. Baker; Grant No. R33MH107589 to Dr. Stern, Grant No. R01MH111794 to Dr. Stern; Grant No. R01 MH081864 to Drs. O’Neill and Piacentini; Grant No. R01 MH085900 to Drs. O’Neill and Feusner, Grant No. K23 MH115206 to Dr. Gruner); the NIMH and the David Judah Fund at the Massachusetts General Hospital (Grant No. K23-MH092397 to Dr. Brennan); the Marató TV3 Foundation (Grants No. 01/2010 and 091710 to Dr. Lazaro); the Carlos III Health Institute (PI040829 to Dr Lazaro, Grant CPII16/00048 and Project Grants PI13/01958 and PI16/00889 to Dr. Soriano-Mas), co-funded by FEDER funds/European Regional Development Fund (ERDF), a way to build Europe; the AGAUR (2017 SGR 881 to Dr. Lazaro); the Michael Smith Foundation for Health Research funding Dr. Jaspers-Fayer and Dr. Stewart; the Carlos III Health Institute (PI14/00419 to Dr. Alonso, Grant No. FI17/00294 to Ignacio Martínez-Zalacaín, Project Grant No. PI16/00950 to Dr. Menchón); the Japan Agency for Medical Research and Development (AMED Brain/MINDS Beyond program Grant No. JP19dm0307002 to Dr. Shimizu); Oxford Health Services Research Committee grant to Dr A James and National Institute on Drug Abuse to Dr. Ivanov (NIH/NIDA Grant No. R21/DA046029 and No. R21/ DA045218); the Wellcome and Royal Society (211155/Z/18/Z) to Tobias U Hauser; the Jacobs Foundation (2017-1261-04) to Tobias U Hauser, the Medical Research Foundation, and the Brain and Behavior Research Foundation (2018 NARSAD Young Investigator grant; 27023) to Tobias U. Hauser; the Swiss National Science Foundation (SNSF 320030_130237) to Susanne Walitza; the Harmann Müller foundation (1460) to Silvia Brem; NHMRC Career Development Fellowship (1140764 to Dr. Schmaal). Publisher Copyright: © 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
AB - No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
UR - http://www.scopus.com/inward/record.url?scp=85092536771&partnerID=8YFLogxK
U2 - 10.1038/s41398-020-01013-y
DO - 10.1038/s41398-020-01013-y
M3 - Article
C2 - 33033241
AN - SCOPUS:85092536771
SN - 2158-3188
VL - 10
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 342
ER -