Meta-Analysis

. 2017 Jan 1;174(1):60-69.

doi: 10.1176/appi.ajp.2016.16020201. Epub 2016 Sep 9.

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis

Premika S W Boedhoe¹, Lianne Schmaal¹, Yoshinari Abe¹, Stephanie H Ameis¹, Paul D Arnold¹, Marcelo C Batistuzzo¹, Francesco Benedetti¹, Jan C Beucke¹, Irene Bollettini¹, Anushree Bose¹, Silvia Brem¹, Anna Calvo¹, Yuqi Cheng¹, Kang Ik K Cho¹, Sara Dallaspezia¹, Damiaan Denys¹, Kate D Fitzgerald¹, Jean-Paul Fouche¹, Mònica Giménez¹, Patricia Gruner¹, Gregory L Hanna¹, Derrek P Hibar¹, Marcelo Q Hoexter¹, Hao Hu¹, Chaim Huyser¹, Keisuke Ikari¹, Neda Jahanshad¹, Norbert Kathmann¹, Christian Kaufmann¹, Kathrin Koch¹, Jun Soo Kwon¹, Luisa Lazaro¹, Yanni Liu¹, Christine Lochner¹, Rachel Marsh¹, Ignacio Martínez-Zalacaín¹, David Mataix-Cols¹, José M Menchón¹, Luciano Minuzzi¹, Takashi Nakamae¹, Tomohiro Nakao¹, Janardhanan C Narayanaswamy¹, Fabrizio Piras¹, Federica Piras¹, Christopher Pittenger¹, Y C Janardhan Reddy¹, Joao R Sato¹, H Blair Simpson¹, Noam Soreni¹, Carles Soriano-Mas¹, Gianfranco Spalletta¹, Michael C Stevens¹, Philip R Szeszko¹, David F Tolin¹, Ganesan Venkatasubramanian¹, Susanne Walitza¹, Zhen Wang¹, Guido A van Wingen¹, Jian Xu¹, Xiufeng Xu¹, Je-Yeon Yun¹, Qing Zhao¹; ENIGMA OCD Working Group; Paul M Thompson¹, Dan J Stein¹, Odile A van den Heuvel¹

Collaborators, Affiliations

Collaborators

ENIGMA OCD Working Group:
Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Nuria Bargalló, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Premika S.W. Boedhoe, Irene Bollettini, Anushree Bose, Silvia Brem, Geraldo F. Busatto, Anna Calvo, Rosa Calvo, Danielle C. Cath, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Froukje E. de Vries, Stella J. de Wit, Damiaan Denys, Yu Fang, Kate D. Fitzgerald, Martine Fontaine, Jean-Paul Fouche, Mònica Giménez, Patricia Gruner, Gregory L. Hanna, Derrek P. Hibar, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Keisuke Ikari, Neda Jahanshad, Norbert Kathmann, Christian Kaufmann, Sabin Khadka, Kathrin Koch, Jun Soo Kwon, Luisa Lazaro, Yanni Liu, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Euripedes C. Miguel, Luciano Minuzzii, Astrid Morer, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y.C. Janardhan Reddy, Joao R. Sato, H. Blair Simpson, Lianne Schmaal, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Dan J. Stein, Michael C. Stevens, Philip R. Szeszko, Paul M. Thompson, David F. Tolin, Dick J. Veltman, Ganesan Venkatasubramanian, Odile A. van den Heuvel, Ysbrand D. van der Werf, Guido A. van Wingen, Susanne Walitza, Zhen Wang, Jian Xu, Xiufeng Xu, Je-Yeon Yun, Qing Zhao

Affiliation

¹ From the Department of Psychiatry and the Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Neuroscience Campus Amsterdam, Free University/VU University Medical Center, Amsterdam; the Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; the Centre for Addiction and Mental Health and Hospital for Sick Children, Toronto; the Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, Canada; the Department of Psychiatry, Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil; Clinical Research Group Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan; the Department of Psychology, Humboldt-Universität zu Berlin, Berlin; the Obsessive-Compulsive Disorder Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India; the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich; Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; the Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China; the Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea; the Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam; the Department of Psychiatry, University of Michigan, Ann Arbor; the Department of Psychiatry, University of Cape Town, Cape Town, South Africa; the Department of Psychiatry, University of Stellenbosch, Cape Town; the Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomèdica en Red de Salud Mental (CIBERSAM), Barcelona; the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; the Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey; De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam; the Department of Child and Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; the Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich; TUM-Neuroimaging Center (TUM-NIC) of Klinikum rechts der Isar, Technische Universität München, Munich; the Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea; the Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; the Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain; SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa; Columbia University Medical Center, New York; the Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute and Columbia University, New York; the Department of Clinical Neuroscience, Center for Psychiatric Research and Education, Karolinska Institutet, Stockholm; the Department of Clinical Sciences, University of Barcelona, Barcelona, Spain; the Mood Disorders Clinic and the Anxiety Treatment and Research Center, St. Joseph's HealthCare, Hamilton, Canada; the Department of Neural Computation for Decision Making, ATR Brain Information Communiciation Research Laboratory Group, Kyoto, Japan; the Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome; the Center of Mathematics, Computation, and Cognition, Universidade Federal Do ABC, Santo Andre, Brazil; the Center for OCD and Related Disorders, New York State Psychiatric Institute, New York; the Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain; the Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; the Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, Hartford, Conn.; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; the James J. Peters VA Medical Center, Bronx, New York; the Institute of Living/Hartford Hospital, Hartford, Conn.; the Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; the Shanghai Key Laboratory of Psychotic Disorders, Shanghai; and the Department of Internal Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, China.

PMID: 27609241
PMCID: PMC5344782
DOI: 10.1176/appi.ajp.2016.16020201

Meta-Analysis

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis

Premika S W Boedhoe et al. Am J Psychiatry. 2017.

. 2017 Jan 1;174(1):60-69.

doi: 10.1176/appi.ajp.2016.16020201. Epub 2016 Sep 9.

Authors

Collaborators

ENIGMA OCD Working Group:
Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Nuria Bargalló, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Premika S.W. Boedhoe, Irene Bollettini, Anushree Bose, Silvia Brem, Geraldo F. Busatto, Anna Calvo, Rosa Calvo, Danielle C. Cath, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Froukje E. de Vries, Stella J. de Wit, Damiaan Denys, Yu Fang, Kate D. Fitzgerald, Martine Fontaine, Jean-Paul Fouche, Mònica Giménez, Patricia Gruner, Gregory L. Hanna, Derrek P. Hibar, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Keisuke Ikari, Neda Jahanshad, Norbert Kathmann, Christian Kaufmann, Sabin Khadka, Kathrin Koch, Jun Soo Kwon, Luisa Lazaro, Yanni Liu, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Euripedes C. Miguel, Luciano Minuzzii, Astrid Morer, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y.C. Janardhan Reddy, Joao R. Sato, H. Blair Simpson, Lianne Schmaal, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Dan J. Stein, Michael C. Stevens, Philip R. Szeszko, Paul M. Thompson, David F. Tolin, Dick J. Veltman, Ganesan Venkatasubramanian, Odile A. van den Heuvel, Ysbrand D. van der Werf, Guido A. van Wingen, Susanne Walitza, Zhen Wang, Jian Xu, Xiufeng Xu, Je-Yeon Yun, Qing Zhao

Affiliation

¹ From the Department of Psychiatry and the Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Neuroscience Campus Amsterdam, Free University/VU University Medical Center, Amsterdam; the Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; the Centre for Addiction and Mental Health and Hospital for Sick Children, Toronto; the Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, Canada; the Department of Psychiatry, Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil; Clinical Research Group Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan; the Department of Psychology, Humboldt-Universität zu Berlin, Berlin; the Obsessive-Compulsive Disorder Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India; the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich; Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; the Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China; the Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea; the Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam; the Department of Psychiatry, University of Michigan, Ann Arbor; the Department of Psychiatry, University of Cape Town, Cape Town, South Africa; the Department of Psychiatry, University of Stellenbosch, Cape Town; the Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomèdica en Red de Salud Mental (CIBERSAM), Barcelona; the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; the Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, University of Southern California, Marina del Rey; De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam; the Department of Child and Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; the Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Munich; TUM-Neuroimaging Center (TUM-NIC) of Klinikum rechts der Isar, Technische Universität München, Munich; the Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea; the Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; the Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain; SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa; Columbia University Medical Center, New York; the Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute and Columbia University, New York; the Department of Clinical Neuroscience, Center for Psychiatric Research and Education, Karolinska Institutet, Stockholm; the Department of Clinical Sciences, University of Barcelona, Barcelona, Spain; the Mood Disorders Clinic and the Anxiety Treatment and Research Center, St. Joseph's HealthCare, Hamilton, Canada; the Department of Neural Computation for Decision Making, ATR Brain Information Communiciation Research Laboratory Group, Kyoto, Japan; the Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome; the Center of Mathematics, Computation, and Cognition, Universidade Federal Do ABC, Santo Andre, Brazil; the Center for OCD and Related Disorders, New York State Psychiatric Institute, New York; the Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain; the Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; the Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, Hartford, Conn.; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; the James J. Peters VA Medical Center, Bronx, New York; the Institute of Living/Hartford Hospital, Hartford, Conn.; the Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; the Shanghai Key Laboratory of Psychotic Disorders, Shanghai; and the Department of Internal Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, China.

PMID: 27609241
PMCID: PMC5344782
DOI: 10.1176/appi.ajp.2016.16020201

Erratum in

CORRECTION.
[No authors listed] [No authors listed] Am J Psychiatry. 2016 Oct 1;173(10):1049. doi: 10.1176/appi.ajp.2016.17310correction. Am J Psychiatry. 2016. PMID: 27690550 No abstract available.
CORRECTION.
[No authors listed] [No authors listed] Am J Psychiatry. 2017 Feb 1;174(2):190. doi: 10.1176/appi.ajp.2017.1742correction. Am J Psychiatry. 2017. PMID: 28142279 No abstract available.

Abstract

Objective: Structural brain imaging studies in obsessive-compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta- and mega-analyses of data from OCD sites worldwide.

Method: T₁ images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta-analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients.

Results: The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results.

Conclusions: The results indicate different patterns of subcortical abnormalities in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.

Keywords: FreeSurfer; Neurodevelopmental disorder; Neuroimaging; Obsessive-Compulsive Disorder; Psychiatry; Structural MRI.

PubMed Disclaimer

Conflict of interest statement

Disclosures: All authors have no conflicts of interest related to this study.

Figures

**Figure 1**
**(a)** Cohen’s d-effect sizes 95% CI for differences in subcortical brain volumes between adult OCD patients and healthy controls. **(b)** Cohen’s d-effect sizes 95% CI for differences in subcortical brain volumes between unmedicated pediatric OCD patients and pediatric healthy controls. Effect sizes were corrected for age, sex, and intracranial volume.

See this image and copyright information in PMC

Comment in

Association and Causation in Brain Imaging in the Case of OCD: Response to McKay et al.
Boedhoe PSW, Schmaal L, Mataix-Cols D, Jahanshad N; ENIGMA OCD Working Group; Thompson PM, Stein D, van den Heuvel OA. Boedhoe PSW, et al. Am J Psychiatry. 2017 Jun 1;174(6):597-599. doi: 10.1176/appi.ajp.2017.17010019r. Am J Psychiatry. 2017. PMID: 28565945 Free PMC article. No abstract available.
Association and Causation in Brain Imaging: The Case of OCD.
McKay D, Abramovitch A, Abramowitz JS, Deacon B. McKay D, et al. Am J Psychiatry. 2017 Jun 1;174(6):597. doi: 10.1176/appi.ajp.2017.17010019. Am J Psychiatry. 2017. PMID: 28565955 No abstract available.

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Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis

Collaborators

Affiliation

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis

Authors

Collaborators

Affiliation

Erratum in

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical