Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.
Journal: Biological psychiatry
Volume: 84
Issue: 9
Year of Publication: 2019
Affiliated Institutions: Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California. Electronic address: tvanerp@uci.edu. Imaging Genetics and Neuroinformatics Lab, Georgia State University, Atlanta, Georgia. 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. 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. Department of Psychology, Georgia State University, Atlanta, Georgia. Department of Psychiatry, Yale University, New Haven, Connecticut; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut. Division of Cerebral Integration, National Institute for Physiological Sciences, Okazaki, Aichi, Japan. 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. Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico. Department of Psychiatry, University of New Mexico, Albuquerque, New Mexico; Mind Research Network, Albuquerque, New Mexico. 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. Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota. Department of Psychiatry and Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. 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. 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. 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. 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. Institute of Clinical Medicine, Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway. 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. Division of Mental Health and Addiction, NORMENT, K.G. Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway. 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. 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. 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. 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. 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. 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. Department of Psychiatry, Monash University, Melbourne, Victoria, Australia; School of Psychiatry, University of New South Wales, New South Wales, Australia. Discipline of Psychiatry, School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia. School of Medical Sciences, University of New South Wales, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia. School of Psychiatry, University of New South Wales, New South Wales, Australia; Neuroscience Research Australia, Sydney, New South Wales, Australia. 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. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Western Australia, Australia. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia; Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia. School of Psychology, University of Newcastle, Newcastle, New South Wales, Australia. Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia. 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. School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia. Murdoch Children's Research Institute, Melbourne, Victoria, Australia. 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. Priority Research Centre for Brain & Mental Health, University of Newcastle, Newcastle, New South Wales, Australia. 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. Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland. Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. 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. Department of Psychiatry, University of California, San Diego, La Jolla, California. Department of Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, California; San Francisco Veterans Affairs Medical Center, San Francisco, California. Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, California. Department of Psychiatry, University of Iowa, Iowa City, Iowa. Brain Imaging and Analysis Center, Duke University Medical Center, Durham, North Carolina. Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California. Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China. Chongqing Three Gorges Central Hospital, Chongqing, China. Zhumadian Psychiatry Hospital, Henan Province, Zhumadian, China. Luoyang Fifth People's Hospital, Henan Province, Luoyang, China. Mind Research Network, Albuquerque, New Mexico; Department of Psychiatry, University of Iowa, Iowa City, Iowa; Advanced Biomedical Informatics Group, LLC, Iowa City, Iowa. 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. 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. Mind Research Network, Albuquerque, New Mexico. Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota; Minneapolis VA Health Care System, Minneapolis, Minnesota. Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Department of Psychiatry & Psychology, Maastricht University, Maastricht, The Netherlands. Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. 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. Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy. 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. 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. 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. Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland. 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. Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California. Centre for Addiction and Mental Health, Toronto, Canada. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. 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. 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. University of Basel Psychiatric Hospital, Basel, Switzerland. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 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. 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. 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. Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy. Istituto Di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. 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. Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Hospital, Seoul, Republic of Korea. 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. Mental Health Research Center, Moscow, Russia. Children's Clinical and Research Institute of Emergency Surgery and Trauma, Moscow, Russia. Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Services, Stockholm County Council, Stockholm, Sweden. Laboratory of Psychiatric Neuroimaging, Laboratórios de Investigação Médica , Department of Psychiatry, Faculty of Medicine, and Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, São Paulo, Brazil. National Institute of Mental Health, Klecany, Czech Republic. 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. 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. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom. Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany. Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. 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. 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. Research Group in Psychiatry, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia. 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. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois. Imaging Genetics and Neuroinformatics Lab, Georgia State University, Atlanta, Georgia; Mind Research Network, Albuquerque, New Mexico.
Abstract summary
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.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.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.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.Authors & Co-authors: van Erp Walton Hibar Schmaal Jiang Glahn Pearlson Yao Fukunaga Hashimoto Okada Yamamori Bustillo Clark Agartz Mueller Cahn de Zwarte Hulshoff Pol Kahn Ophoff van Haren Andreassen Dale Doan Gurholt Hartberg Haukvik Jørgensen Lagerberg Melle Westlye Gruber Kraemer Richter Zilles Calhoun Crespo-Facorro Roiz-Santiañez Tordesillas-Gutiérrez Loughland Carr Catts Cropley Fullerton Green Henskens Jablensky Lenroot Mowry Michie Pantelis Quidé Schall Scott Cairns Seal Tooney Rasser Cooper Shannon Weickert Weickert Morris Hong Kochunov Beard Gur Gur Satterthwaite Wolf Belger Brown Ford Macciardi Mathalon O'Leary Potkin Preda Voyvodic Lim McEwen Yang Tan Tan Wang Fan Chen Xiang Tang Guo Wan Wei Bockholt Ehrlich Wolthusen King Shoemaker Sponheim De Haan Koenders Machielsen van Amelsvoort Veltman Assogna Banaj de Rossi Iorio Piras Spalletta McKenna Pomarol-Clotet Salvador Corvin Donohoe Kelly Whelan Dickie Rotenberg Voineskos Ciufolini Radua Dazzan Murray Reis Marques Simmons Borgwardt Egloff Harrisberger Riecher-Rössler Smieskova Alpert Wang Jönsson Koops Sommer Bertolino Bonvino Di Giorgio Neilson Mayer Stephen Kwon Yun Cannon McDonald Lebedeva Tomyshev Akhadov Kaleda Fatouros-Bergman Flyckt Busatto Rosa Serpa Zanetti Hoschl Skoch Spaniel Tomecek Hagenaars McIntosh Whalley Lawrie Knöchel Oertel-Knöchel Stäblein Howells Stein Temmingh Uhlmann Lopez-Jaramillo Dima McMahon Faskowitz Gutman Jahanshad Thompson Turner
Study Outcome
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Citations : Goghari VM, Truong W, Spilka MJ (2015): A magnetic resonance imaging family study of cortical thickness in schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 168: 660–668.Authors : 179
Identifiers
Doi : 10.1016/j.biopsych.2018.04.023SSN : 1873-2402