Meta-Analysis

. 2018 Nov 1;84(9):644-654.

doi: 10.1016/j.biopsych.2018.04.023. Epub 2018 May 14.

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Theo G M van Erp¹, Esther Walton², Derrek P Hibar³, Lianne Schmaal⁴, Wenhao Jiang⁵, David C Glahn⁶, Godfrey D Pearlson⁶, Nailin Yao⁶, Masaki Fukunaga⁷, Ryota Hashimoto⁸, Naohiro Okada⁹, Hidenaga Yamamori¹⁰, Juan R Bustillo¹¹, Vincent P Clark¹², Ingrid Agartz¹³, Bryon A Mueller¹⁴, Wiepke Cahn¹⁵, Sonja M C de Zwarte¹⁵, Hilleke E Hulshoff Pol¹⁵, René S Kahn¹⁵, Roel A Ophoff¹⁶, Neeltje E M van Haren¹⁷, Ole A Andreassen¹⁸, Anders M Dale¹⁹, Nhat Trung Doan²⁰, Tiril P Gurholt²¹, Cecilie B Hartberg²⁰, Unn K Haukvik¹⁸, Kjetil N Jørgensen²¹, Trine V Lagerberg²², Ingrid Melle¹⁸, Lars T Westlye²³, Oliver Gruber²⁴, Bernd Kraemer²⁴, Anja Richter²⁴, David Zilles²⁵, Vince D Calhoun¹², Benedicto Crespo-Facorro²⁶, Roberto Roiz-Santiañez²⁶, Diana Tordesillas-Gutiérrez²⁷, Carmel Loughland²⁸, Vaughan J Carr²⁹, Stanley Catts³⁰, Vanessa L Cropley³¹, Janice M Fullerton³², Melissa J Green³³, Frans A Henskens³⁴, Assen Jablensky³⁵, Rhoshel K Lenroot³³, Bryan J Mowry³⁶, Patricia T Michie³⁷, Christos Pantelis³⁸, Yann Quidé³³, Ulrich Schall³⁹, Rodney J Scott⁴⁰, Murray J Cairns⁴⁰, Marc Seal⁴¹, Paul A Tooney⁴², Paul E Rasser⁴³, Gavin Cooper⁴³, Cynthia Shannon Weickert³³, Thomas W Weickert³³, Derek W Morris⁴⁴, Elliot Hong⁴⁵, Peter Kochunov⁴⁵, Lauren M Beard⁴⁶, Raquel E Gur⁴⁶, Ruben C Gur⁴⁶, Theodore D Satterthwaite⁴⁶, Daniel H Wolf⁴⁶, Aysenil Belger⁴⁷, Gregory G Brown⁴⁸, Judith M Ford⁴⁹, Fabio Macciardi⁵⁰, Daniel H Mathalon⁴⁹, Daniel S O'Leary⁵¹, Steven G Potkin⁵⁰, Adrian Preda⁵⁰, James Voyvodic⁵², Kelvin O Lim¹⁴, Sarah McEwen⁵³, Fude Yang⁵⁴, Yunlong Tan⁵⁴, Shuping Tan⁵⁴, Zhiren Wang⁵⁴, Fengmei Fan⁵⁴, Jingxu Chen⁵⁴, Hong Xiang⁵⁵, Shiyou Tang⁵⁵, Hua Guo⁵⁶, Ping Wan⁵⁶, Dong Wei⁵⁷, Henry J Bockholt⁵⁸, Stefan Ehrlich⁵⁹, Rick P F Wolthusen⁶⁰, Margaret D King⁶¹, Jody M Shoemaker⁶¹, Scott R Sponheim⁶², Lieuwe De Haan⁶³, Laura Koenders⁶³, Marise W Machielsen⁶³, Therese van Amelsvoort⁶⁴, Dick J Veltman⁶⁵, Francesca Assogna⁶⁶, Nerisa Banaj⁶⁷, Pietro de Rossi⁶⁸, Mariangela Iorio⁶⁷, Fabrizio Piras⁶⁶, Gianfranco Spalletta⁶⁹, Peter J McKenna⁷⁰, Edith Pomarol-Clotet⁷⁰, Raymond Salvador⁷⁰, Aiden Corvin⁷¹, Gary Donohoe⁴⁴, Sinead Kelly⁷², Christopher D Whelan⁷³, Erin W Dickie⁷⁴, David Rotenberg⁷⁴, Aristotle N Voineskos⁷⁴, Simone Ciufolini⁷⁵, Joaquim Radua⁷⁶, Paola Dazzan⁷⁷, Robin Murray⁷⁵, Tiago Reis Marques⁷⁵, Andrew Simmons⁷⁵, Stefan Borgwardt⁷⁸, Laura Egloff⁷⁸, Fabienne Harrisberger⁷⁸, Anita Riecher-Rössler⁷⁸, Renata Smieskova⁷⁸, Kathryn I Alpert⁷⁹, Lei Wang⁸⁰, Erik G Jönsson⁸¹, Sanne Koops¹⁵, Iris E C Sommer⁸², Alessandro Bertolino⁸³, Aurora Bonvino⁸⁴, Annabella Di Giorgio⁸⁴, Emma Neilson⁸⁵, Andrew R Mayer⁶¹, Julia M Stephen⁶¹, Jun Soo Kwon⁸⁶, Je-Yeon Yun⁸⁷, Dara M Cannon⁸⁸, Colm McDonald⁸⁸, Irina Lebedeva⁸⁹, Alexander S Tomyshev⁸⁹, Tolibjohn Akhadov⁹⁰, Vasily Kaleda⁸⁹, Helena Fatouros-Bergman⁹¹, Lena Flyckt⁹¹; Karolinska Schizophrenia Project; Geraldo F Busatto⁹², Pedro G P Rosa⁹², Mauricio H Serpa⁹², Marcus V Zanetti⁹², Cyril Hoschl⁹³, Antonin Skoch⁹⁴, Filip Spaniel⁹³, David Tomecek⁹⁵, Saskia P Hagenaars⁹⁶, Andrew M McIntosh⁹⁷, Heather C Whalley⁸⁵, Stephen M Lawrie⁸⁵, Christian Knöchel⁹⁸, Viola Oertel-Knöchel⁹⁸, Michael Stäblein⁹⁸, Fleur M Howells⁹⁹, Dan J Stein¹⁰⁰, Henk S Temmingh⁹⁹, Anne Uhlmann¹⁰¹, Carlos Lopez-Jaramillo¹⁰², Danai Dima¹⁰³, Agnes McMahon⁷³, Joshua I Faskowitz⁷³, Boris A Gutman¹⁰⁴, Neda Jahanshad⁷³, Paul M Thompson⁷³, Jessica A Turner¹⁰⁵

Collaborators, Affiliations

Collaborators

Karolinska Schizophrenia Project:
Lars Farde, Lena Flyckt, Göran Engberg, Sophie Erhardt, Helena Fatouros-Bergman, Simon Cervenka, Lilly Schwieler, Fredrik Piehl, Ingrid Agartz, Karin Collste, Pauliina Victorsson, Anna Malmqvist, Mikael Hedberg, Funda Orhan

Affiliations

¹ Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California. Electronic address: tvanerp@uci.edu.
² Imaging Genetics and Neuroinformatics Lab, Georgia State University, Atlanta, Georgia.
³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California; Janssen Research & Development, San Diego, California.
⁴ Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Victoria, Australia; Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia; Department of Psychiatry and Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
⁵ Department of Psychology, Georgia State University, Atlanta, Georgia.
⁶ Department of Psychiatry, Yale University, New Haven, Connecticut; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut.
⁷ Division of Cerebral Integration, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
⁸ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
⁹ Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
¹⁰ Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
¹¹ Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico.
¹² Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico; Mind Research Network, Albuquerque, New Mexico.
¹³ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹⁴ Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
¹⁵ Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁶ Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁷ Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
¹⁹ Center for Translational Imaging and Precision Medicine, San Diego, California; Department of Neurosciences, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; Department of Psychiatry, University of California, San Diego, La Jolla, California; Department of Cognitive Science, University of California, San Diego, La Jolla, California.
²⁰ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway.
²¹ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
²² Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
²³ Department of Psychology, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
²⁴ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany; Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry, Georg August University, Göttingen, Germany.
²⁵ Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry, Georg August University, Göttingen, Germany; Department of Psychiatry, University Medical Center Göttingen, Göttingen, Germany.
²⁶ Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, Marqués de Valdecilla Research Institute (IDIVAL), University of Cantabria, Santander, Spain; Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain.
²⁷ Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, Marqués de Valdecilla Research Institute (IDIVAL), University of Cantabria, Santander, Spain; Neuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research Institute, Marqués de Valdecilla Research Institute (IDIVAL), University of Cantabria, Santander, Spain; Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain.
²⁸ Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Hunter New England Local Health District, Newcastle, New South Wales, Australia.
²⁹ Department of Psychiatry, Monash University, Melbourne, Victoria, Australia; School of Psychiatry, University of New South Wales, New South Wales, Australia.
³⁰ Discipline of Psychiatry, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
³¹ Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia.
³² School of Medical Sciences, University of New South Wales, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
³³ School of Psychiatry, University of New South Wales, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
³⁴ Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, New South Wales, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
³⁵ School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Western Australia, Australia.
³⁶ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia; Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia.
³⁷ School of Psychology, University of Newcastle, Newcastle, New South Wales, Australia.
³⁸ Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
³⁹ Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia; Grow Up Well, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁴⁰ School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁴¹ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
⁴² School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁴³ Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia.
⁴⁴ Centre for Neuroimaging & Cognitive Genomics, Clinical Neuroimaging Laboratory, National Centre for Biomedical Engineering (NCBES) Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland; School of Psychology, and Department of Biochemistry, National University of Ireland Galway, Galway, Ireland; Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
⁴⁵ Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
⁴⁶ Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
⁴⁷ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina.
⁴⁸ Department of Psychiatry, University of California, San Diego, La Jolla, California.
⁴⁹ Department of Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, California; San Francisco Veterans Affairs Medical Center, San Francisco, California.
⁵⁰ Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California.
⁵¹ Department of Psychiatry, University of Iowa, Iowa City, Iowa.
⁵² Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina.
⁵³ Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California.
⁵⁴ Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China.
⁵⁵ Chongqing Three Gorges Central Hospital, Chongqing, China.
⁵⁶ Zhumadian Psychiatry Hospital, Henan Province, Zhumadian, China.
⁵⁷ Luoyang Fifth People's Hospital, Henan Province, Luoyang, China.
⁵⁸ Mind Research Network, Albuquerque, New Mexico; Department of Psychiatry, University of Iowa, Iowa City, Iowa; Advanced Biomedical Informatics Group, LLC, Iowa City, Iowa.
⁵⁹ Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts; Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
⁶⁰ Social Neuroscience Laboratory, Charlestown, Massachusetts; Psychiatric Neuroimaging Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
⁶¹ Mind Research Network, Albuquerque, New Mexico.
⁶² Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota; Minneapolis VA Health Care System, Minneapolis, Minnesota.
⁶³ Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁶⁴ Department of Psychiatry & Psychology, Maastricht University, Maastricht, The Netherlands.
⁶⁵ Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
⁶⁶ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Centro Fermi, Museo Storico della Fisica e Centro Studi e Ricerche "Enrico Fermi", Rome, Italy.
⁶⁷ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
⁶⁸ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Dipartimento di Neuroscienze, Salute Mentale e Organi di Senso (NESMOS), Faculty of Medicine and Psychology, and Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
⁶⁹ Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas; Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
⁷⁰ Fundación para la Investigación y Docencia Maria Angustias Giménez (FIDMAG) Germanes Hospitalaries Research Foundation, Barcelona, Spain; Centro Investigación Biomédica en Red de Salud Mental, Barcelona, Spain.
⁷¹ Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
⁷² Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
⁷³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
⁷⁴ Centre for Addiction and Mental Health, Toronto, Canada.
⁷⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁶ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Fundación para la Investigación y Docencia Maria Angustias Giménez (FIDMAG) Germanes Hospitalaries Research Foundation, Barcelona, Spain; Centro Investigación Biomédica en Red de Salud Mental, Barcelona, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁷ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, London, United Kingdom.
⁷⁸ University of Basel Psychiatric Hospital, Basel, Switzerland.
⁷⁹ Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
⁸⁰ Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
⁸¹ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁸² Department of Neuroscience, University Medical Center Groningen, Rijks Universiteit Groningen, Groningen, The Netherlands; Department of Psychiatry, University Medical Center Groningen, Rijks Universiteit Groningen, Groningen, The Netherlands.
⁸³ Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy.
⁸⁴ Istituto Di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
⁸⁵ Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
⁸⁶ 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.
⁸⁷ Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Hospital, Seoul, Republic of Korea.
⁸⁸ Centre for Neuroimaging & Cognitive Genomics, Clinical Neuroimaging Laboratory, National Centre for Biomedical Engineering (NCBES) Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
⁸⁹ Mental Health Research Center, Moscow, Russia.
⁹⁰ Children's Clinical and Research Institute of Emergency Surgery and Trauma, Moscow, Russia.
⁹¹ Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Services, Stockholm County Council, Stockholm, Sweden.
⁹² Laboratory of Psychiatric Neuroimaging, Laboratórios de Investigação Médica 21, Department of Psychiatry, Faculty of Medicine, and Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, São Paulo, Brazil.
⁹³ National Institute of Mental Health, Klecany, Czech Republic.
⁹⁴ 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.
⁹⁵ National Institute of Mental Health, Klecany, Czech Republic; Institute of Computer Science, Czech Academy of Sciences, Czech Technical University in Prague, Prague, Czech Republic; Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
⁹⁶ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
⁹⁷ Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
⁹⁸ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
⁹⁹ Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
¹⁰⁰ Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
¹⁰¹ Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
¹⁰² Research Group in Psychiatry, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia.
¹⁰³ Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Psychology, City, University of London, London, United Kingdom.
¹⁰⁴ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois.
¹⁰⁵ Imaging Genetics and Neuroinformatics Lab, Georgia State University, Atlanta, Georgia; Mind Research Network, Albuquerque, New Mexico.

PMID: 29960671
PMCID: PMC6177304
DOI: 10.1016/j.biopsych.2018.04.023

Meta-Analysis

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Theo G M van Erp et al. Biol Psychiatry. 2018.

. 2018 Nov 1;84(9):644-654.

doi: 10.1016/j.biopsych.2018.04.023. Epub 2018 May 14.

Authors

Collaborators

Karolinska Schizophrenia Project:
Lars Farde, Lena Flyckt, Göran Engberg, Sophie Erhardt, Helena Fatouros-Bergman, Simon Cervenka, Lilly Schwieler, Fredrik Piehl, Ingrid Agartz, Karin Collste, Pauliina Victorsson, Anna Malmqvist, Mikael Hedberg, Funda Orhan

Affiliations

¹ Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California. Electronic address: tvanerp@uci.edu.
² Imaging Genetics and Neuroinformatics Lab, Georgia State University, Atlanta, Georgia.
³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California; Janssen Research & Development, San Diego, California.
⁴ Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Victoria, Australia; Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia; Department of Psychiatry and Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
⁵ Department of Psychology, Georgia State University, Atlanta, Georgia.
⁶ Department of Psychiatry, Yale University, New Haven, Connecticut; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut.
⁷ Division of Cerebral Integration, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
⁸ Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
⁹ Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
¹⁰ Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
¹¹ Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico.
¹² Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico; Mind Research Network, Albuquerque, New Mexico.
¹³ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹⁴ Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota.
¹⁵ Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁶ Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁷ Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
¹⁹ Center for Translational Imaging and Precision Medicine, San Diego, California; Department of Neurosciences, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; Department of Psychiatry, University of California, San Diego, La Jolla, California; Department of Cognitive Science, University of California, San Diego, La Jolla, California.
²⁰ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway.
²¹ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
²² Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
²³ Department of Psychology, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
²⁴ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany; Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry, Georg August University, Göttingen, Germany.
²⁵ Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry, Georg August University, Göttingen, Germany; Department of Psychiatry, University Medical Center Göttingen, Göttingen, Germany.
²⁶ Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, Marqués de Valdecilla Research Institute (IDIVAL), University of Cantabria, Santander, Spain; Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain.
²⁷ Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, Marqués de Valdecilla Research Institute (IDIVAL), University of Cantabria, Santander, Spain; Neuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research Institute, Marqués de Valdecilla Research Institute (IDIVAL), University of Cantabria, Santander, Spain; Centro Investigación Biomédica en Red de Salud Mental, Santander, Spain.
²⁸ Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia; Hunter New England Local Health District, Newcastle, New South Wales, Australia.
²⁹ Department of Psychiatry, Monash University, Melbourne, Victoria, Australia; School of Psychiatry, University of New South Wales, New South Wales, Australia.
³⁰ Discipline of Psychiatry, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
³¹ Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia.
³² School of Medical Sciences, University of New South Wales, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
³³ School of Psychiatry, University of New South Wales, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia.
³⁴ Priority Research Centre for Health Behaviour, University of Newcastle, Newcastle, New South Wales, Australia; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
³⁵ School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Western Australia, Australia.
³⁶ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia; Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia.
³⁷ School of Psychology, University of Newcastle, Newcastle, New South Wales, Australia.
³⁸ Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
³⁹ Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia; Grow Up Well, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁴⁰ School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁴¹ Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
⁴² School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
⁴³ Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia.
⁴⁴ Centre for Neuroimaging & Cognitive Genomics, Clinical Neuroimaging Laboratory, National Centre for Biomedical Engineering (NCBES) Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland; School of Psychology, and Department of Biochemistry, National University of Ireland Galway, Galway, Ireland; Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
⁴⁵ Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
⁴⁶ Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania.
⁴⁷ Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina.
⁴⁸ Department of Psychiatry, University of California, San Diego, La Jolla, California.
⁴⁹ Department of Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, California; San Francisco Veterans Affairs Medical Center, San Francisco, California.
⁵⁰ Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California.
⁵¹ Department of Psychiatry, University of Iowa, Iowa City, Iowa.
⁵² Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina.
⁵³ Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California.
⁵⁴ Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China.
⁵⁵ Chongqing Three Gorges Central Hospital, Chongqing, China.
⁵⁶ Zhumadian Psychiatry Hospital, Henan Province, Zhumadian, China.
⁵⁷ Luoyang Fifth People's Hospital, Henan Province, Luoyang, China.
⁵⁸ Mind Research Network, Albuquerque, New Mexico; Department of Psychiatry, University of Iowa, Iowa City, Iowa; Advanced Biomedical Informatics Group, LLC, Iowa City, Iowa.
⁵⁹ Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts; Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
⁶⁰ Social Neuroscience Laboratory, Charlestown, Massachusetts; Psychiatric Neuroimaging Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
⁶¹ Mind Research Network, Albuquerque, New Mexico.
⁶² Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota; Minneapolis VA Health Care System, Minneapolis, Minnesota.
⁶³ Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁶⁴ Department of Psychiatry & Psychology, Maastricht University, Maastricht, The Netherlands.
⁶⁵ Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
⁶⁶ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Centro Fermi, Museo Storico della Fisica e Centro Studi e Ricerche "Enrico Fermi", Rome, Italy.
⁶⁷ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
⁶⁸ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Dipartimento di Neuroscienze, Salute Mentale e Organi di Senso (NESMOS), Faculty of Medicine and Psychology, and Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
⁶⁹ Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas; Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
⁷⁰ Fundación para la Investigación y Docencia Maria Angustias Giménez (FIDMAG) Germanes Hospitalaries Research Foundation, Barcelona, Spain; Centro Investigación Biomédica en Red de Salud Mental, Barcelona, Spain.
⁷¹ Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
⁷² Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
⁷³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
⁷⁴ Centre for Addiction and Mental Health, Toronto, Canada.
⁷⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁶ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Fundación para la Investigación y Docencia Maria Angustias Giménez (FIDMAG) Germanes Hospitalaries Research Foundation, Barcelona, Spain; Centro Investigación Biomédica en Red de Salud Mental, Barcelona, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁷⁷ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, London, United Kingdom.
⁷⁸ University of Basel Psychiatric Hospital, Basel, Switzerland.
⁷⁹ Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
⁸⁰ Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
⁸¹ Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁸² Department of Neuroscience, University Medical Center Groningen, Rijks Universiteit Groningen, Groningen, The Netherlands; Department of Psychiatry, University Medical Center Groningen, Rijks Universiteit Groningen, Groningen, The Netherlands.
⁸³ Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy.
⁸⁴ Istituto Di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
⁸⁵ Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
⁸⁶ 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.
⁸⁷ Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Hospital, Seoul, Republic of Korea.
⁸⁸ Centre for Neuroimaging & Cognitive Genomics, Clinical Neuroimaging Laboratory, National Centre for Biomedical Engineering (NCBES) Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
⁸⁹ Mental Health Research Center, Moscow, Russia.
⁹⁰ Children's Clinical and Research Institute of Emergency Surgery and Trauma, Moscow, Russia.
⁹¹ Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Services, Stockholm County Council, Stockholm, Sweden.
⁹² Laboratory of Psychiatric Neuroimaging, Laboratórios de Investigação Médica 21, Department of Psychiatry, Faculty of Medicine, and Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, São Paulo, Brazil.
⁹³ National Institute of Mental Health, Klecany, Czech Republic.
⁹⁴ 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.
⁹⁵ National Institute of Mental Health, Klecany, Czech Republic; Institute of Computer Science, Czech Academy of Sciences, Czech Technical University in Prague, Prague, Czech Republic; Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
⁹⁶ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
⁹⁷ Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
⁹⁸ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
⁹⁹ Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
¹⁰⁰ Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
¹⁰¹ Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
¹⁰² Research Group in Psychiatry, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia.
¹⁰³ Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Psychology, City, University of London, London, United Kingdom.
¹⁰⁴ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois.
¹⁰⁵ Imaging Genetics and Neuroinformatics Lab, Georgia State University, Atlanta, Georgia; Mind Research Network, Albuquerque, New Mexico.

PMID: 29960671
PMCID: PMC6177304
DOI: 10.1016/j.biopsych.2018.04.023

Abstract

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.

Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.

Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.

Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Keywords: Cortical; Imaging; Meta-analysis; Schizophrenia; Surface area; Thickness.

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Conflict of interest statement

CONFLICTS OF INTEREST

Dr. Van Erp has had a research contract with Otsuka Pharmaceuticals, Inc. Adrian Preda has served as a consultant for Boehringer Ingelheim. The remaining authors report no biomedical financial interests or potential conflicts of interest.

Figures

**Figure 1.**
Cortical map of regional Cohen’s d effect sizes for schizophrenia versus healthy group cortical thickness contrast statistically controlling for A) age and sex, and B) age, sex, and global cortical thickness. Only regions with pFDR<0.05 are depicted in color. In figure 1B, warm colors (yellow-red) reflect regions in which the effect of schizophrenia is more than than the mean global cortical thinning, and cool colors (green-blue) reflect regions where the effect of schizophrenia is less than the mean global thinning compared to controls.

**Figure 2.**
Cohen’s d effect sizes for schizophrenia versus healthy group cortical thickness contrast statistically controlling for age, sex, and global mean cortical thickness. Only regions with pFDR<0.05 are depicted in color.

**Figure 3.**
Cortical map of regional Cohen’s d effect sizes for schizophrenia versus healthy group cortical surface area contrast statistically controlling for A) age and sex, and B) age, sex, and total cortical surface area. Only regions with pFDR<0.05 are depicted in color. In figure 3B, warm colors (yellow-red) would reflect regions in which the effect of schizophrenia is more than the mean lower lower surface area, and cool colors (green-blue) reflect regions where the effect of schizophrenia is less than the mean lower global surface area compared to controls.

**Figure 4.**
A) Cohen’s d effect sizes, and B) least square mean percent difference for schizophrenia versus healthy group contrasts in global cortical thickness, statistically controlling for age, and sex, by medication group and hemisphere. Nominal one-tailed p-values for left (L) and right (R) hemisphere thickness group comparisons, statistically controlling for age and sex, were: Second-Generation vs. Unmedicated [p(L)<0.05; p(R)<0.06]; First-Generation vs. Unmedicated [p(L)<0.01; p(R)<0.002]; Both First-Generation and Second-Generation vs. Unmedicated [p(L)<0.02; p<0.05]; First-Generation vs. Second-Generation [p(L)<0.03; p(R)<0.03]; Both First-Generation and Second-Generation vs. Second-Generation [p(L)<0.02; p(R)<0.05]; Both First-Generation and Second-Generation vs. First-Generation [p(L)=0.50; p(R)=0.48]; Supplementary Tables S16–S21).

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Comment in

The Power of Collaboration and Data Aggregation.
Barch DM. Barch DM. Biol Psychiatry. 2018 Nov 1;84(9):626-628. doi: 10.1016/j.biopsych.2018.06.005. Biol Psychiatry. 2018. PMID: 30297020 No abstract available.
New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?
Vita A, De Peri L. Vita A, et al. Biol Psychiatry. 2019 Apr 1;85(7):e33. doi: 10.1016/j.biopsych.2018.07.029. Epub 2018 Nov 22. Biol Psychiatry. 2019. PMID: 30470560 No abstract available.
Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?
van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, Pearlson GD, Yao N, Fukunaga M, Hashimoto R, Okada N, Yamamori H, Clark VP, Mueller BA, de Zwarte SMC, Ophoff RA, van Haren NEM, Andreassen OA, Gurholt TP, Gruber O, Kraemer B, Richter A, Calhoun VD, Crespo-Facorro B, Roiz-Santiañez R, Tordesillas-Gutiérrez D, Loughland C, Catts S, Fullerton JM, Green MJ, Henskens F, Jablensky A, Mowry BJ, Pantelis C, Quidé Y, Schall U, Scott RJ, Cairns MJ, Seal M, Tooney PA, Rasser PE, Cooper G, Shannon Weickert C, Weickert TW, Hong E, Kochunov P, Gur RE, Gur RC, Ford JM, Macciardi F, Mathalon DH, Potkin SG, Preda A, Fan F, Ehrlich S, King MD, De Haan L, Veltman DJ, Assogna F, Banaj N, de Rossi P, Iorio M, Piras F, Spalletta G, Pomarol-Clotet E, Kelly S, Ciufolini S, Radua J, Murray R, Marques TR, Simmons A, Borgwardt S, Schönborn-Harrisberger F, Riecher-Rössler A, Smieskova R, Alpert KI, Bertolino A, Bonvino A, Di Giorgio A, Neilson E, Mayer AR, Yun JY, Cannon DM, Lebedeva I, Tomyshev AS, Akhadov T, Kaleda V, Fatouros-Bergman H, Flyckt L; Karolinska Schizophrenia Project; Rosa PGP, Serpa MH, Zanetti MV, Hoschl C, Skoch A, Spaniel F, Tomecek D, McIntosh AM, Whalley HC, Knöchel C, Oert… See abstract for full author list ➔ van Erp TGM, et al. Biol Psychiatry. 2019 Apr 1;85(7):e35-e39. doi: 10.1016/j.biopsych.2018.10.003. Epub 2018 Nov 22. Biol Psychiatry. 2019. PMID: 30470561 Free PMC article. No abstract available.

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Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

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Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

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