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, Paul M Thompson1, Dan J Stein1, Odile A van den Heuvel1. 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.
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.
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 OCDpatients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCDpatients 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 OCDpatients. 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 OCDpatients. 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.
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