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New Research
Published Online: 1 March 2014
Multicenter Voxel-Based Morphometry Mega-Analysis of Structural Brain Scans in Obsessive-Compulsive Disorder
Stella J. de Wit, M.D., Pino Alonso, M.D., Ph.D., Lizanne Schweren, M.Sc., David Mataix-Cols, Ph.D., Christine Lochner, Ph.D., José M. Menchón, M.D., Ph.D., Dan J. Stein, M.D., Ph.D., … Show All … , Jean-Paul Fouche, M.Sc., Carles Soriano-Mas, Ph.D., Joao R. Sato, Ph.D., Marcelo Q. Hoexter, M.D., Ph.D., Damiaan Denys, M.D., Ph.D., Takashi Nakamae, M.D., Ph.D., Seiji Nishida, M.D., Ph.D., Jun Soo Kwon, M.D., Ph.D., Joon Hwan Jang, M.D., Ph.D., Geraldo F. Busatto, M.D., Ph.D., Narcís Cardoner, M.D., Ph.D., Danielle C. Cath, M.D., Ph.D., Kenji Fukui, M.D., Ph.D., Wi Hoon Jung, Ph.D., Sung Nyun Kim, M.D., Euripides C. Miguel, M.D., Ph.D., Jin Narumoto, M.D., Ph.D., Mary L. Phillips, M.D., Ph.D., Jesus Pujol, M.D., Ph.D., Peter L. Remijnse, M.D., Ph.D., Yuki Sakai, M.D., Ph.D., Na Young Shin, M.A., Kei Yamada, M.D., Ph.D., Dick J. Veltman, M.D., Ph.D., and Odile A. van den Heuvel, M.D., Ph.D. Show FewerAuthors Info & Affiliations
Publication: American Journal of Psychiatry
Abstract
Objective
Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables.
Method
A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects.
Results
Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age).
Conclusions
These findings partially support the prevailing fronto-striatal models of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction.
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Information & Authors
Information
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History
Received: 29 April 2013
Revision received: 28 August 2013
Accepted: 12 September 2013
Published online: 1 March 2014
Published in print: March 2014
Authors
Affiliations
Stella J. de Wit, M.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Pino Alonso, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Lizanne Schweren, M.Sc.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
David Mataix-Cols, Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Christine Lochner, Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
José M. Menchón, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Dan J. Stein, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Jean-Paul Fouche, M.Sc.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Carles Soriano-Mas, Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Joao R. Sato, Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Marcelo Q. Hoexter, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Damiaan Denys, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Takashi Nakamae, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Seiji Nishida, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Jun Soo Kwon, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Joon Hwan Jang, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Geraldo F. Busatto, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Narcís Cardoner, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Danielle C. Cath, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Kenji Fukui, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Wi Hoon Jung, Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Sung Nyun Kim, M.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Euripides C. Miguel, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Jin Narumoto, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Mary L. Phillips, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Jesus Pujol, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Peter L. Remijnse, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Yuki Sakai, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Na Young Shin, M.A.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Kei Yamada, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Dick J. Veltman, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Odile A. van den Heuvel, M.D., Ph.D.
From the Departments of Psychiatry and of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Department of Psychiatry, Bellvitge University Hospital-Bellvitge Institute for Biomedical Research (IDIBELL), University of Barcelona, Barcelona, Spain; Carlos III Health Institute, Center for Biomedical Research Network on Mental Health (CIBERSAM), Barcelona; Institute of Psychiatry, King’s College London, London; MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; Departments of Human Biology and of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Center of Mathematics, Computation, and Cognition, Federal University of ABC, Santo André, Brazil; Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, Academic Medical Center, Amsterdam; Departments of Psychiatry and Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; and CRC-Hospital del Mar, Barcelona.
Notes
Address correspondence to Dr. van den Heuvel ([email protected]).
Funding Information
The authors report no financial relationships with commercial interests.
Supplementary Material
Supported by the Dutch Organization for Scientific Research (NWO) (grants 912-02-050, 907-00-012, 940-37-018, and 916.86.038); the Carlos III Health Institute (PI09/01331, PI10/01753, PI10/01003, CP10/00604, and CIBER-CB06/03/0034); the Agency for Administration of University and Research (AGAUR, Barcelona; 2009SGR1554); a “Miguel Servet” contract from the Carlos III Health Institute (CP10/00604) to Dr. Soriano-Mas; Ministry of Education, Culture, Sports, Science, and Technology (Japan) Grants-in-Aid for Young Scientists to Dr. Narumoto (23591724) and to Dr. Nakamae (24791223); Wellcome Trust project grant 064846; a grant from the Foundation for the Support of Research in the State of São Paulo (FAPESP) to Dr. Miguel (2005/55628-8); a FAPESP scholarship to Dr. Hoexter (2005/04206-6); and a National Research Foundation of Korea grant funded by the Korean government (Ministry of Education, Science, and Technology, 2012-0005150).Metrics & Citations
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