Review

. 2022 Jan;43(1):23-36.

doi: 10.1002/hbm.24972. Epub 2020 Mar 10.

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration

Odile A van den Heuvel^{1

2}, Premika S W Boedhoe¹, Sara Bertolin³, Willem B Bruin⁴, Clyde Francks^{5

6}, Iliyan Ivanov⁷, Neda Jahanshad⁸, Xiang-Zhen Kong⁵, Jun Soo Kwon^{9

10}, Joseph O'Neill¹¹, Tomas Paus¹², Yash Patel¹², Fabrizio Piras¹³, Lianne Schmaal^{14

15}, Carles Soriano-Mas^{3

16

17}, Gianfranco Spalletta^{13

18}, Guido A van Wingen⁴, Je-Yeon Yun^{19

20}, Chris Vriend¹, H Blair Simpson²¹, Daan van Rooij⁶, Marcelo Q Hoexter²², Martine Hoogman^{6

23}, Jan K Buitelaar⁶, Paul Arnold²⁴, Jan C Beucke^{25

26}, Francesco Benedetti²⁷, Irene Bollettini²⁷, Anushree Bose²⁸, Brian P Brennan²⁹, Alessandro S De Nadai³⁰, Kate Fitzgerald³¹, Patricia Gruner³², Edna Grünblatt^{33

34

35}, Yoshiyuki Hirano³⁶, Chaim Huyser³⁷, Anthony James³⁸, Kathrin Koch³⁹, Gerd Kvale², Luisa Lazaro⁴⁰, Christine Lochner⁴¹, Rachel Marsh²¹, David Mataix-Cols²⁷, Pedro Morgado^{42

43

44}, Takashi Nakamae⁴⁵, Tomohiro Nakao⁴⁶, Janardhanan C Narayanaswamy²⁸, Erika Nurmi⁴⁷, Christopher Pittenger⁴⁸, Y C Janardhan Reddy²⁶, João R Sato⁴⁹, Noam Soreni⁵⁰, S Evelyn Stewart^{51

52

53}, Stephan F Taylor³¹, David Tolin⁵⁴, Sophia I Thomopoulos⁸, Dick J Veltman¹, Ganesan Venkatasubramanian²⁸, Susanne Walitza³¹, Zhen Wang^{55

56}, Paul M Thompson⁸, Dan J Stein⁵⁷; ENIGMA-OCD working group

Collaborators, Affiliations

Collaborators

ENIGMA-OCD working group:
Yoshinari Abe, Pino Alonso, Francesca Assogna, Nerisa Banaj, Marcelo C Batistuzzo, Silvia Brem, Valentina Ciullo, Jamie Feusner, Ignacio Martínez-Zalacaín, José M Menchón, Euripedes C Miguel, John Piacentini, Federica Piras, Yuki Sakai, Lidewij Wolters, Kei Yamada

Affiliations

¹ Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
² Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway.
³ Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.
⁴ Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Language & Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
⁶ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
⁷ Icahn School of Medicine at Mount Sinai, New York, New York.
⁸ Keck USC School of Medicine, Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Marina del Rey, California.
⁹ Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
¹⁰ Department of Brain & Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
¹¹ Division of Child & Adolescent Psychiatry, UCLA Jane & Terry Semel Institute For Neuroscience, Los Angeles, California.
¹² Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, Toronto, Ontario, Canada.
¹³ Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
¹⁴ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.
¹⁵ Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia.
¹⁶ Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
¹⁷ Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁸ Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texsas.
¹⁹ Seoul National University Hospital, Seoul, Republic of Korea.
²⁰ Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
²¹ Center for OC and Related Disorders at the New York State Psychiatric Institute and Columbia University Irving Medical Center, New York, New York.
²² Departamento e Instituto de Psiquiatria do Hospital das Clinicas, IPQ HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
²³ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
²⁴ Mathison Centre for Mental Health Research & Education and Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁵ Humboldt-Universität zu Berlin, Department of Psychology, Berlin, Germany.
²⁶ Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
²⁷ Department of Psychiatry and Clinical Psychobiology, Scientific Institute Ospedale, Milan, Italy.
²⁸ Obsessive-Compulsive Disorder (OCD) Clinic Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
²⁹ McLean Hospital, Harvard Medical School, Belmont, Massachusetts.
³⁰ Department of Psychology, Texas State University, San Marcos, Texas.
³¹ Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan.
³² Department of Psychiatry, Yale University, New Haven, Connecticut.
³³ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland.
³⁴ Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
³⁵ Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
³⁶ Research Center for Child Mental Development, Chiba University, Chiba, Japan.
³⁷ De Bascule, academic center child and adolescent psychiatry, Amsterdam, The Netherlands.
³⁸ Department of Psychiatry, University of Oxford, Oxford, UK.
³⁹ Department of Neuroradiology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
⁴⁰ Department of Child and Adolescent Psychiatry and Psychology, IDIBAPS, CIBERSAM, Department of Medicine, Faculty of Barcelona, Barcelona, Spain.
⁴¹ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Matieland, South Africa.
⁴² Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
⁴³ ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
⁴⁴ Clinical Academic Center-Braga, Braga, Portugal.
⁴⁵ Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴⁶ Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan.
⁴⁷ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California.
⁴⁸ OCD Research Clinic, Yale University, New Haven, Connecticut.
⁴⁹ Center of Mathematics, Computing and Cognition, Universidade Federal do ABC, Santo André, Brazil.
⁵⁰ Pediatric OCD Consultation Service, Anxiety Treatment and Research Center, McMaster University, Hamilton, Ontario, Canada.
⁵¹ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
⁵² BC Mental Health and Addictions Research Institute, Vancouver, British Columbia, Canada.
⁵³ BC Children's Hospital, Vancouver, British Columbia, Canada.
⁵⁴ Anxiety Disorders Center, The Institute of Living, Hartford, Connecticut.
⁵⁵ Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵⁶ Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China.
⁵⁷ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

PMID: 32154629
PMCID: PMC8675414
DOI: 10.1002/hbm.24972

Review

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration

Odile A van den Heuvel et al. Hum Brain Mapp. 2022 Jan.

. 2022 Jan;43(1):23-36.

doi: 10.1002/hbm.24972. Epub 2020 Mar 10.

Authors

Collaborators

ENIGMA-OCD working group:
Yoshinari Abe, Pino Alonso, Francesca Assogna, Nerisa Banaj, Marcelo C Batistuzzo, Silvia Brem, Valentina Ciullo, Jamie Feusner, Ignacio Martínez-Zalacaín, José M Menchón, Euripedes C Miguel, John Piacentini, Federica Piras, Yuki Sakai, Lidewij Wolters, Kei Yamada

Affiliations

¹ Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
² Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway.
³ Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain.
⁴ Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Language & Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.
⁶ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
⁷ Icahn School of Medicine at Mount Sinai, New York, New York.
⁸ Keck USC School of Medicine, Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Marina del Rey, California.
⁹ Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
¹⁰ Department of Brain & Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
¹¹ Division of Child & Adolescent Psychiatry, UCLA Jane & Terry Semel Institute For Neuroscience, Los Angeles, California.
¹² Holland Bloorview Kids Rehabilitation Hospital, Bloorview Research Institute, Toronto, Ontario, Canada.
¹³ Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome, Italy.
¹⁴ Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.
¹⁵ Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia.
¹⁶ Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
¹⁷ Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁸ Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texsas.
¹⁹ Seoul National University Hospital, Seoul, Republic of Korea.
²⁰ Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
²¹ Center for OC and Related Disorders at the New York State Psychiatric Institute and Columbia University Irving Medical Center, New York, New York.
²² Departamento e Instituto de Psiquiatria do Hospital das Clinicas, IPQ HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
²³ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
²⁴ Mathison Centre for Mental Health Research & Education and Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
²⁵ Humboldt-Universität zu Berlin, Department of Psychology, Berlin, Germany.
²⁶ Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
²⁷ Department of Psychiatry and Clinical Psychobiology, Scientific Institute Ospedale, Milan, Italy.
²⁸ Obsessive-Compulsive Disorder (OCD) Clinic Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
²⁹ McLean Hospital, Harvard Medical School, Belmont, Massachusetts.
³⁰ Department of Psychology, Texas State University, San Marcos, Texas.
³¹ Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan.
³² Department of Psychiatry, Yale University, New Haven, Connecticut.
³³ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, University of Zurich, Zurich, Switzerland.
³⁴ Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
³⁵ Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
³⁶ Research Center for Child Mental Development, Chiba University, Chiba, Japan.
³⁷ De Bascule, academic center child and adolescent psychiatry, Amsterdam, The Netherlands.
³⁸ Department of Psychiatry, University of Oxford, Oxford, UK.
³⁹ Department of Neuroradiology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
⁴⁰ Department of Child and Adolescent Psychiatry and Psychology, IDIBAPS, CIBERSAM, Department of Medicine, Faculty of Barcelona, Barcelona, Spain.
⁴¹ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Matieland, South Africa.
⁴² Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
⁴³ ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
⁴⁴ Clinical Academic Center-Braga, Braga, Portugal.
⁴⁵ Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴⁶ Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan.
⁴⁷ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California.
⁴⁸ OCD Research Clinic, Yale University, New Haven, Connecticut.
⁴⁹ Center of Mathematics, Computing and Cognition, Universidade Federal do ABC, Santo André, Brazil.
⁵⁰ Pediatric OCD Consultation Service, Anxiety Treatment and Research Center, McMaster University, Hamilton, Ontario, Canada.
⁵¹ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
⁵² BC Mental Health and Addictions Research Institute, Vancouver, British Columbia, Canada.
⁵³ BC Children's Hospital, Vancouver, British Columbia, Canada.
⁵⁴ Anxiety Disorders Center, The Institute of Living, Hartford, Connecticut.
⁵⁵ Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵⁶ Institute of Psychological and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China.
⁵⁷ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

PMID: 32154629
PMCID: PMC8675414
DOI: 10.1002/hbm.24972

Abstract

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Keywords: ENIGMA; MRI; cortical thickness; mega-analysis; meta-analysis; obsessive-compulsive disorder; surface area; volume.

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Figures

**FIGURE 1**
World map showing the 34 institutes participating in the ENIGMA‐OCD consortium

**FIGURE 2**
Summary of the subcortical volume effects in ENIGMA‐OCD (based on Boedhoe et al., Am J Psychiatry)

**FIGURE 3**
Summary of the cortical thickness effects in adult OCD patients compared to healthy controls in ENIGMA‐OCD, in relation to medication status (based on Boedhoe et al., Am J Psychiatry). Negative effect sizes d (ranging from light orange d = −0.05 to dark red d = −0.15) indicate thinner cortex in OCD compared to controls

See this image and copyright information in PMC

References

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An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration

Collaborators

Affiliations

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration

Authors

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Affiliations

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