NeuroImage (Sep 2020)
Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA
- Joaquim Radua,
- Eduard Vieta,
- Russell Shinohara,
- Peter Kochunov,
- Yann Quidé,
- Melissa J. Green,
- Cynthia S. Weickert,
- Thomas Weickert,
- Jason Bruggemann,
- Tilo Kircher,
- Igor Nenadić,
- Murray J. Cairns,
- Marc Seal,
- Ulrich Schall,
- Frans Henskens,
- Janice M. Fullerton,
- Bryan Mowry,
- Christos Pantelis,
- Rhoshel Lenroot,
- Vanessa Cropley,
- Carmel Loughland,
- Rodney Scott,
- Daniel Wolf,
- Theodore D. Satterthwaite,
- Yunlong Tan,
- Kang Sim,
- Fabrizio Piras,
- Gianfranco Spalletta,
- Nerisa Banaj,
- Edith Pomarol-Clotet,
- Aleix Solanes,
- Anton Albajes-Eizagirre,
- Erick J. Canales-Rodríguez,
- Salvador Sarro,
- Annabella Di Giorgio,
- Alessandro Bertolino,
- Michael Stäblein,
- Viola Oertel,
- Christian Knöchel,
- Stefan Borgwardt,
- Stefan du Plessis,
- Je-Yeon Yun,
- Jun Soo Kwon,
- Udo Dannlowski,
- Tim Hahn,
- Dominik Grotegerd,
- Clara Alloza,
- Celso Arango,
- Joost Janssen,
- Covadonga Díaz-Caneja,
- Wenhao Jiang,
- Vince Calhoun,
- Stefan Ehrlich,
- Kun Yang,
- Nicola G. Cascella,
- Yoichiro Takayanagi,
- Akira Sawa,
- Alexander Tomyshev,
- Irina Lebedeva,
- Vasily Kaleda,
- Matthias Kirschner,
- Cyril Hoschl,
- David Tomecek,
- Antonin Skoch,
- Therese van Amelsvoort,
- Geor Bakker,
- Anthony James,
- Adrian Preda,
- Andrea Weideman,
- Dan J. Stein,
- Fleur Howells,
- Anne Uhlmann,
- Henk Temmingh,
- Carlos López-Jaramillo,
- Ana Díaz-Zuluaga,
- Lydia Fortea,
- Eloy Martinez-Heras,
- Elisabeth Solana,
- Sara Llufriu,
- Neda Jahanshad,
- Paul Thompson,
- Jessica Turner,
- Theo van Erp,
- David Glahn,
- Godfrey Pearlson,
- Elliot Hong,
- Axel Krug,
- Vaughan Carr,
- Paul Tooney,
- Gavin Cooper,
- Paul Rasser,
- Patricia Michie,
- Stanley Catts,
- Raquel Gur,
- Ruben Gur,
- Fude Yang,
- Fengmei Fan,
- Jingxu Chen,
- Hua Guo,
- Shuping Tan,
- Zhiren Wang,
- Hong Xiang,
- Federica Piras,
- Francesca Assogna,
- Raymond Salvador,
- Peter McKenna,
- Aurora Bonvino,
- Margaret King,
- Stefan Kaiser,
- Dana Nguyen,
- Julian Pineda-Zapata
Affiliations
- Joaquim Radua
- Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBERSAM, Madrid, Spain; Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Clinical Neuroscience, Stockholm Health Care Services, Stockholm County Council, Karolinska Institutet, Stockholm, Sweden; Corresponding author. Imaging of Mood- and Anxiety-Related Disorders (IMARD) group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
- Eduard Vieta
- CIBERSAM, Madrid, Spain; Bipolar and depressive disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Barcelona Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain; University of Barcelona, Barcelona, Spain
- Russell Shinohara
- Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA; Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA
- Peter Kochunov
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
- Yann Quidé
- School of Psychiatry, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia
- Melissa J. Green
- School of Psychiatry, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia
- Cynthia S. Weickert
- School of Psychiatry, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia; Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, Newyork, NY, USA
- Thomas Weickert
- School of Psychiatry, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia
- Jason Bruggemann
- School of Psychiatry, University of New South Wales, Sydney, NSW, Australia; Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA
- Tilo Kircher
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
- Igor Nenadić
- Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany
- Murray J. Cairns
- University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia
- Marc Seal
- Murdoch Children's Research Institute, Melbourne, VIC, Australia; The University of Melbourne, Australia
- Ulrich Schall
- University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia
- Frans Henskens
- Health Behaviour Research Group, School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
- Janice M. Fullerton
- School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia
- Bryan Mowry
- Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Queensland Centre for Mental Health Research, The University of Queensland, Brisbane, QLD, Australia
- Christos Pantelis
- Melbourne Neuropsychiatry Centre, Dept. of Psychiatry, University of Melbourne, Melbourne, VIC, Australia; North Western Mental Health, Melbourne Health, Melbourne, VIC, Australia
- Rhoshel Lenroot
- School of Psychiatry, University of New South Wales, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia; University of New Mexico, Albuquerque, NM, USA
- Vanessa Cropley
- Melbourne Neuropsychiatry Centre, Dept. of Psychiatry, University of Melbourne, Melbourne, VIC, Australia
- Carmel Loughland
- University of Newcastle, Newcastle, NSW, Australia
- Rodney Scott
- University of Newcastle, Newcastle, NSW, Australia
- Daniel Wolf
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
- Theodore D. Satterthwaite
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
- Yunlong Tan
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
- Kang Sim
- West Region and Research Division, Institute of Mental Health, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Fabrizio Piras
- Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
- Gianfranco Spalletta
- Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA
- Nerisa Banaj
- Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
- Edith Pomarol-Clotet
- CIBERSAM, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
- Aleix Solanes
- Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBERSAM, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, School of Medicine, Autonomous University of Barcelona, Barcelona, Spain
- Anton Albajes-Eizagirre
- Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; CIBERSAM, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
- Erick J. Canales-Rodríguez
- CIBERSAM, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; Signal Processing Lab (LTS5), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
- Salvador Sarro
- CIBERSAM, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain
- Annabella Di Giorgio
- IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, Bari, Italy
- Alessandro Bertolino
- Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, Bari, Italy
- Michael Stäblein
- Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, Frankfurt, Germany
- Viola Oertel
- Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, Frankfurt, Germany
- Christian Knöchel
- Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, Frankfurt, Germany
- Stefan Borgwardt
- Department of Psychiatry, University of Basel, Basel, Switzerland; Department of Psychiatry and Psychotherapy, University Lübeck, Germany
- Stefan du Plessis
- University of Stellenbosch, Cape Town, Western Province, South Africa
- Je-Yeon Yun
- Seoul National University Hospital, Seoul, Republic of Korea; Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea
- Jun Soo Kwon
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Brain & Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
- Udo Dannlowski
- Department of Psychiatry, University of Münster, Münster, Germany
- Tim Hahn
- Department of Psychiatry, University of Münster, Münster, Germany
- Dominik Grotegerd
- Department of Psychiatry, University of Münster, Münster, Germany
- Clara Alloza
- CIBERSAM, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Celso Arango
- CIBERSAM, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain
- Joost Janssen
- CIBERSAM, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Covadonga Díaz-Caneja
- CIBERSAM, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain
- Wenhao Jiang
- Georgia State University, Atlanta, GA, USA
- Vince Calhoun
- Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, GA, USA
- Stefan Ehrlich
- Technische Universität Dresden, Faculty of Medicine, Division of Psychological and Social Medicine, Dresden, Germany
- Kun Yang
- Departments of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Nicola G. Cascella
- Departments of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Yoichiro Takayanagi
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Akira Sawa
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Departments of Psychiatry, Neuroscience, and Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Alexander Tomyshev
- Mental Health Research Center, Moscow, Russia
- Irina Lebedeva
- Mental Health Research Center, Moscow, Russia
- Vasily Kaleda
- Mental Health Research Center, Moscow, Russia
- Matthias Kirschner
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland; Montreal Neurological Institute, McGill University, Montreal, Canada
- Cyril Hoschl
- National Institute of Mental Health, Klecany, Czech Republic; Department of Psychiatry and Clinical Psychology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
- David Tomecek
- National Institute of Mental Health, Klecany, Czech Republic; Institute of Computer Science, Czech Academy of Sciences, Prague, Czech Republic; Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic
- Antonin Skoch
- National Institute of Mental Health, Klecany, Czech Republic; MR Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Therese van Amelsvoort
- Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
- Geor Bakker
- Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands
- Anthony James
- Department of Psychiatry, University of Oxford, Oxford, UK
- Adrian Preda
- Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA
- Andrea Weideman
- Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA
- Dan J. Stein
- SAMRC Unit on Risk & Resilience in Mental Disorders, Dept of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, Western Province, South Africa
- Fleur Howells
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa
- Anne Uhlmann
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa; Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Dresden, Germany
- Henk Temmingh
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa; Valkenburg Hospital, Observatory, Cape Town, Western Cape, South Africa
- Carlos López-Jaramillo
- Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Antioquia, Colombia; Mood Disorders Program, Hospital Universitario San Vicente Fundación, Medellin, Colombia
- Ana Díaz-Zuluaga
- Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Antioquia, Colombia
- Lydia Fortea
- Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Eloy Martinez-Heras
- University of Barcelona, Barcelona, Spain; Center of Neuroimmunology. Laboratory of Advanced Imaging in Neuroimmunological Diseases. Hospital Clinic de Barcelona, Barcelona, Spain; Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Elisabeth Solana
- University of Barcelona, Barcelona, Spain; Center of Neuroimmunology. Laboratory of Advanced Imaging in Neuroimmunological Diseases. Hospital Clinic de Barcelona, Barcelona, Spain; Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Sara Llufriu
- University of Barcelona, Barcelona, Spain; Center of Neuroimmunology. Laboratory of Advanced Imaging in Neuroimmunological Diseases. Hospital Clinic de Barcelona, Barcelona, Spain; Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Neda Jahanshad
- Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Paul Thompson
- Imaging Genetics Center, Department of Neurology, University of Southern California, Los Angeles, CA, USA
- Jessica Turner
- Georgia State University, Atlanta, GA, USA
- Theo van Erp
- Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California Irvine, 309 Qureshey Research Lab, Irvine, CA, 92697, USA
- David Glahn
- Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA
- Godfrey Pearlson
- Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA; Depts. of Psychiatry and Neuroscience, Yale University, New Haven, CT, USA
- Elliot Hong
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
- Axel Krug
- Philipps-University Marburg, Marburg, Germany
- Vaughan Carr
- University of New South Wales, Sydney, NSW, Australia; Monash University, Melbourne, VIC, Australia
- Paul Tooney
- University of Newcastle, Newcastle, NSW, Australia; Hunter Medical Research Institute, Newcastle, NSW, Australia
- Gavin Cooper
- University of Newcastle, Newcastle, NSW, Australia
- Paul Rasser
- University of Newcastle, Newcastle, NSW, Australia
- Patricia Michie
- University of Newcastle, Newcastle, NSW, Australia
- Stanley Catts
- University of Queensland, Brisbane, QLD, Australia
- Raquel Gur
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
- Ruben Gur
- Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
- Fude Yang
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
- Fengmei Fan
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
- Jingxu Chen
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
- Hua Guo
- Zhumadian Psychiatry Hospital, Zhumadian, Henan province, China
- Shuping Tan
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
- Zhiren Wang
- Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China
- Hong Xiang
- Chongqing Three Gorges Central Hospital, Chongqing, China
- Federica Piras
- Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
- Francesca Assogna
- Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
- Raymond Salvador
- CIBERSAM, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
- Peter McKenna
- CIBERSAM, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
- Aurora Bonvino
- Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari ‘Aldo Moro’, Bari, Italy
- Margaret King
- University of New Mexico, Albuquerque, NM, USA; Mind Research Network, Albuquerque, NM, USA
- Stefan Kaiser
- Geneva University Hospitals, Geneva, Switzerland
- Dana Nguyen
- Department of Pediatrics, University of California Irvine, Irvine, CA, USA
- Julian Pineda-Zapata
- Research Group, Instituto de Alta Tecnología Médica (IATM), Medellín, Antioquia, Colombia
- Journal volume & issue
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Vol. 218
p. 116956
Abstract
A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).
