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Biol Psychiatry. 2019 Apr 30. pii: S0006-3223(19)31292-2. doi: 10.1016/j.biopsych.2019.04.022. [Epub ahead of print]

Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium.

Collaborators (137)

Kong XZ, Boedhoe PSW, Abe Y, Alonso P, Ameis SH, Anticevic A, Arnold PD, Assogna F, Baker JT, Banaj N, Bargalló N, Batistuzzo MC, Benedetti F, Beucke JC, Bollettini I, Bose A, Brandeis D, Brem S, Brennan BP, Buitelaar J, Busatto GF, Calvo A, Calvo R, Cheng Y, Cho KIK, Ciullo V, Dallaspezia S, Denys D, de Vries FE, de Wit SJ, Dickie E, Drechsler R, Ely BA, Esteves M, Falini A, Fang Y, Feusner J, Figee M, Fitzgerald KD, Fontaine M, Fouche JP, Fridgeirsson EA, Gruner P, Gürsel DA, Hall G, Hamatani S, Hanna GL, Hansen B, Hauser TU, Hirano Y, Hoexter MQ, Hu H, Huyser C, Ikari K, Jahanshad N, James A, Jaspers-Fayer F, Kathmann N, Kaufmann C, Koch K, Kuno M, Kvale G, Kwon JS, Lazaro L, Liu Y, Lochner C, Magalhães R, Marques P, Marsh R, Martínez-Zalacaín I, Masuda Y, Mataix-Cols D, Matsumoto K, McCracken JT, Menchón JM, Miguel EC, Minuzzi L, Moreira PS, Morer A, Morgado P, Nakagawa A, Nakamae T, Nakao T, Narayanaswamy JC, Narumoto J, Nishida S, Nurmi EL, O'Neill J, Pariente JC, Perriello C, Piacentini J, Piras F, Piras F, Pittenger C, Poletti S, Reddy YCJ, Reess T, Rus-Oswald OG, Sakai Y, Sato JR, Schmaal L, Shimizu E, Simpson HB, Soreni N, Soriano-Mas C, Sousa N, Spalletta G, Stern ER, Stevens MC, Stewart SE, Szeszko PR, Takahashi J, Tang J, Thorsen AL, Tolin DF, Tsuchiyagaito A, van Rooij D, van Wingen GA, van der Werf YD, Veltman DJ, Vecchio D, Venkatasubramanian G, Walitza S, Wang Z, Watanabe A, Xu J, Xu X, Yamada K, Yoshida T, Yun JY, Zarei M, Zhao Q, Zhou C, Thompson PM, Stein DJ, van den Heuvel OA, Francks C.

Author information

1
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands. Electronic address: xiangzhen.kong@outlook.com.
2
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
3
Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
4
Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-Institut d'Investigació Biomédica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental-CIBERSAM, University of Barcelona, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
5
The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, The Centre for Addiction and Mental Health, Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Alberta; Centre for Brain and Mental Health, The Hospital for Sick Children, Toronto, Alberta.
6
Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute, Calgary, Alberta; Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta.
7
Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.
8
McLean Hopsital, Harvard Medical School, Belmont, Massachusetts.
9
Departamento e Instituto de Psiquiatria do Hospital das Clinicas, IPQ HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
10
Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy.
11
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
12
Obsessive-Compulsive Disorder Clinic, Department of Psychiatry National Institute of Mental Health and Neurosciences, Bangalore, India.
13
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; Neuroscience Center Zürich, University of Zürich and Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland.
14
Department of Cognitive Neuroscience, Radboud University, Nijmegen, The Netherlands.
15
Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain; Department of Medicine, University of Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
16
Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Shanghai, People's Republic of China.
17
Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
18
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands; Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
19
Department of Neuroscience, Graduate School of Biomedical Sciences, New York, New York.
20
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
21
Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.
22
Department of Psychiatry, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa.
23
Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
24
Department of Psychiatry, New Haven, Connecticut; Olin Neuropsychiatric Research Center, Olin Neuropsychiatry Research Center, Hartford, Connecticut.
25
Department of Psychiatry, New Haven, Connecticut.
26
Department of Neuroradiology, Technische Universität München, München, Germany; TUM-Neuroimaging Center (TUM-NIC) of Klinikum Rechts der Isar, Technische Universität München, München, Germany.
27
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, United Kingdom; Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom.
28
Research Center for Child Mental Development, Chiba University, Chiba, Japan.
29
Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
30
Department of Child and Adolescent Psychiatry, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands; De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands.
31
Department of Psychiatry, Oxford University, Oxford, United Kingdom.
32
University of British Columbia, British Columbia Children's Hospital, Vancouver, British Columbia.
33
OCD Team, Haukeland University Hospital, Bergen, Norway; Department of Clinical Psychology, University of Bergen, Bergen, Norway.
34
Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.
35
Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain; Department of Medicine, University of Barcelona, Universitat Autònoma de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
36
SU/UCT MRC Unit on Anxiety and Stress Disorders, University of Stellenbosch, Cape Town, South Africa.
37
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Braga/Guimarães, Portugal; Clinical Academic Center-Braga, Braga, Braga/Guimarães, Portugal; Life and Health Sciences Research Institute (ICVS)/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
38
Columbia University Irving Medical Center, New York State Psychiatric Institute, Columbia University, New York, New York; The Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, New York.
39
Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-Institut d'Investigació Biomédica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
40
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
41
Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland.
42
Mood Disorders Clinic, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
43
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
44
Magnetic Resonance Image Core Facility, Universitat Autònoma de Barcelona, Barcelona, Spain.
45
McLean Hopsital, Harvard Medical School, Belmont, Massachusetts; University of Illinois at Urbana-Champaign, Champaign, Illinois.
46
University of Zürich, University Hospital Zürich; Department of Neuroradiology, Zürich, Switzerland.
47
Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; ATR Brain Information Communication Research Laboratory Group, Kyoto, Japan.
48
Center of Mathematics, Computing and Cognition, Universidade Federal do ABC, Santo Andre, Brazil.
49
Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
50
Columbia University Irving Medical Center, New York State Psychiatric Institute, Columbia University, New York, New York; Center for OCD and Related Disorders, New York State Psychiatric Institute, New York, New York.
51
Pediatric OCD Consultation Service, Anxiety Treatment and Research Center, St. Joseph's Healthcare, Hamilton, Ontario, Canada.
52
Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-Institut d'Investigació Biomédica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental-CIBERSAM, University of Barcelona, Barcelona, Spain; Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
53
Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy; Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.
54
Department of Psychiatry, New York University School of Medicine, New York, New York; Nathan Kline Institute for Psychiatric Research, Orangeburg, New York.
55
Yale University School of Medicine, New Haven, Connecticut; Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, Hartford, Connecticut.
56
Department of Psychiatry, British Columbia Children's Hospital, Vancouver, British Columbia; Provincial Obsessive-Compulsive Disorder Program, British Columbia Children's Hospital, Vancouver, British Columbia.
57
Icahn School of Medicine at Mount Sinai, New York State Psychiatric Institute, Columbia University, New York, New York; James J. Peters VA Medical Center, New York, New York.
58
Yale University School of Medicine, New Haven, Connecticut; Institute of Living/Hartford Hospital, Hartford, Connecticut.
59
Research Center for Child Mental Development, Chiba University, Chiba, Japan; Laureate Institute for Brain Research, Tulsa, Oklahoma.
60
Shanghai Mental Health Center, Shanghai, People's Republic of China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People's Republic of China.
61
Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Hospital, Seoul, Republic of Korea.
62
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
63
SU/UCT MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
64
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands. Electronic address: clyde.francks@mpi.nl.

Abstract

BACKGROUND:

Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.

METHODS:

We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.

RESULTS:

In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.

CONCLUSIONS:

The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

KEYWORDS:

Brain asymmetry; Laterality; Mega-analysis; Obsessive-compulsive disorder; Pallidum; Thalamus

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