Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium
Year: 2018
Type: review
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.
Source: Biological Psychiatry
Authors: Theo G.M. van Erp, Esther Walton, Derrek P. Hibar, Lianne Schmaal, Wenhao Jiang, David C. Glahn, Godfrey D. Pearlson, Nailin Yao, Masaki Fukunaga, Ryota Hashimoto, Naohiro Okada, Hidenaga Yamamori, Juan R. Bustillo, Vincent P. Clark, Ingrid Agartz, Bryon A. Mueller, Wiepke Cahn, Sonja M.C. de Zwarte, Hilleke E. Hulshoff Pol, René S. Kahn, Roel A. Ophoff, Neeltje E.M. van Haren, Ole A. Andreassen, Anders M. Dale, Nhat Trung Doan, Tiril P. Gurholt, Cecilie B. Hartberg, Unn K. Haukvik, Kjetil N. Jørgensen, Trine V. Lagerberg, Ingrid Melle, Lars T. Westlye, Oliver Gruber, Bernd Kraemer, Anja Richter, David Zilles, Vince D. Calhoun, Benedicto Crespo-Facorro, Roberto Roiz-Santiañez, Diana Tordesillas-Gutiérrez, Carmel Loughland, Vaughan J. Carr, Stanley Catts, Vanessa L. Cropley, Janice M. Fullerton, Melissa J. Green, Frans A. Henskens, Assen Jablensky, Rhoshel K. Lenroot, Bryan J. Mowry, Patricia T. Michie, Christos Pantelis, Yann Quidé, Ulrich Schall, Rodney J. Scott, Murray J. Cairns, Marc Seal, Paul A. Tooney, Paul E. Rasser, Gavin Cooper, Cynthia Shannon Weickert, Thomas W. Weickert, Derek W. Morris, Elliot Hong, Peter Kochunov, Lauren M. Beard, Raquel E. Gur, Ruben C. Gur, Theodore D. Satterthwaite, Daniel H. Wolf, Aysenil Belger, Gregory G. Brown, Judith M. Ford, Fabio Macciardi, Daniel H. Mathalon, Daniel S. O’Leary, Steven G. Potkin, Adrian Preda, James Voyvodic, Kelvin O. Lim, Sarah McEwen, Fude Yang, Yunlong Tan, Shuping Tan, Zhiren Wang, Fengmei Fan, Jingxu Chen, Hong Xiang, Shiyou Tang, Hua Guo, Ping Wan, Dong Wei, Henry J. Bockholt, Stefan Ehrlich, Rick P.F. Wolthusen, Margaret D. King, Jody M. Shoemaker, Scott R. Sponheim, Lieuwe De Haan, Laura Koenders, Marise W. Machielsen, Therese van Amelsvoort, Dick J. Veltman, Francesca Assogna, Nerisa Banaj, Pietro de Rossi, Mariangela Iorio, Fabrizio Piras, Gianfranco Spalletta, Peter J. McKenna, Edith Pomarol-Clotet, Raymond Salvador, Aiden Corvin, Gary Donohoe, Sinead Kelly, Christopher D. Whelan, Erin W. Dickie, David Rotenberg, Aristotle N. Voineskos, Simone Ciufolini, Joaquim Radua, Paola Dazzan, Robin Murray, Tiago Reis Marques, Andrew Simmons, Stefan Borgwardt, Laura Egloff, Fabienne Harrisberger, Anita Riecher-Rössler, Renata Smieskova, Kathryn I. Alpert, Lei Wang, Erik G. Jönsson, Sanne Koops, Iris E.C. Sommer, Alessandro Bertolino, Aurora Bonvino, Annabella Di Giorgio, Emma Neilson, Andrew R. Mayer, Julia M. Stephen, Jun Soo Kwon, Je-Yeon Yun, Dara M. Cannon, Colm McDonald, Irina Lebedeva, Alexander S. Tomyshev, Tolibjohn Akhadov, Vasily Kaleda, Helena Fatouros-Bergman, Lena Flyckt, Geraldo F. Busatto, Pedro G.P. Rosa, Mauricio H. Serpa, Marcus V. Zanetti, Cyril Hoschl, Antonin Skoch, Filip Spaniel, David Tomecek, Saskia P. Hagenaars, Andrew M. McIntosh, Heather C. Whalley, Stephen M. Lawrie, Christian Knöchel, Viola Oertel-Knöchel, Michael Stäblein, Fleur M. Howells, Dan J. Stein, Henk S. Temmingh, Anne Uhlmann, Carlos Lopez-Jaramillo, Danai Dima, Agnes McMahon, Joshua I. Faskowitz, Boris A. Gutman, Neda Jahanshad, Paul M. Thompson, Jessica A. Turner, 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
Institutions: University of California, Irvine, Georgia State University, University of Southern California, The University of Melbourne, Orygen, Amsterdam UMC Location Vrije Universiteit Amsterdam, Hartford Hospital, Yale University, National Institute for Physiological Sciences, Molecular Research Center for Children's Mental Development, The University of Osaka, The University of Tokyo, University of New Mexico, Mind Research Network, University of Oslo, Karolinska Institutet, Diakonhjemmet Hospital, University of Minnesota, University Medical Center Utrecht, University of California, Los Angeles, Erasmus MC, Oslo University Hospital, University of California San Diego, Heidelberg University, University Hospital Heidelberg, University of Göttingen, Universitätsmedizin Göttingen, Universidad de Cantabria, Centro de Investigación Biomédica en Red de Salud Mental, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Hunter Medical Research Institute, Hunter New England Local Health District, University of Newcastle Australia, UNSW Sydney, Monash University, The University of Queensland, Neuroscience Research Australia, The University of Western Australia, Queensland Centre for Mental Health Research, Florey Institute of Neuroscience and Mental Health, Murdoch Children's Research Institute, Ollscoil na Gaillimhe – University of Galway, Trinity College Dublin, University of Maryland, Baltimore, University of Pennsylvania, University of North Carolina at Chapel Hill, Duke University, Duke Medical Center, San Francisco VA Medical Center, University of California, San Francisco, University of Iowa, Beijing HuiLongGuan Hospital, Chongqing Three Gorges Central Hospital, Zhumadian Central Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Technische Universität Dresden, Harvard University, Massachusetts General Hospital, Minneapolis VA Health Care System, Minneapolis VA Medical Center, Amsterdam UMC Location University of Amsterdam, University of Amsterdam, Maastricht University, Centro Ricerche Enrico Fermi, Fondazione Santa Lucia, Sapienza University of Rome, Baylor College of Medicine, Fidmag Sisters Hospitallers, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Centre for Addiction and Mental Health, King's College London, South London and Maudsley NHS Foundation Trust, National Institute for Health and Care Research, University of Basel, Northwestern University, University Medical Center Groningen, University of Groningen, University of Bari Aldo Moro, Casa Sollievo della Sofferenza, University of Edinburgh, Seoul National University, Seoul National University Hospital, Mental Health Research Center of Russian Academy of Medical Sciences, Research Institute of Emergency Childrens Surgery and Traumatology, Region Stockholm, Stockholm Health Care Services, Universidade de São Paulo, National Institute of Mental Health, Institute of Clinical and Experimental Medicine, Czech Academy of Sciences, Czech Academy of Sciences, Institute of Computer Science, Czech Technical University in Prague, Goethe University Frankfurt, University Hospital Frankfurt, University of Cape Town, Groote Schuur Hospital, Stellenbosch University, Universidad de Antioquia, City, University of London, Illinois Institute of Technology
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,489
Funders: U.S. Department of Veterans Affairs, Eli Lilly and Company, Brigham and Women's Hospital, Massachusetts General Hospital, Yale University, University of Southern California, University of Pennsylvania, Northwestern University, University of Minnesota, České Vysoké Učení Technické v Praze, Universität Basel, South London and Maudsley NHS Foundation Trust, National University of Ireland, Wellcome Trust, Hunter New England Local Health District, Children’s Hospital of Wisconsin Research Institute, Neuroscience Research Australia, Murdoch Children's Research Institute, Universitätsmedizin Göttingen, National Institute for Health and Care Research, King's College London, Hunter Medical Research Institute, University of Galway, University of New South Wales, Monash University, Universiteit van Amsterdam, Vrije Universiteit Amsterdam, Universiteit Maastricht, Seoul National University, Technische Universität Dresden, Karolinska Institutet, Akademie Věd České Republiky, Sapienza Università di Roma, Seoul National University Hospital, Stockholms Läns Landsting, Universiteit Stellenbosch, Universitair Medisch Centrum Groningen, Universidad de Antioquia, Universitetet i Oslo, Universidade de São Paulo, Universidad de Cantabria, Centre d'Imagerie BioMédicale, University of Cape Town, Diakonhjemmet, Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Centre for Cognitive Ageing and Cognitive Epidemiology, Instituto de Investigación Marqués de Valdecilla, Universitätsklinikum Heidelberg, National Institutes of Health, University of California, Los Angeles, City, University of London, University of North Carolina at Chapel Hill, University of California, San Diego, University of California, San Francisco, Feinberg School of Medicine, University of California, Irvine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, College of Medicine, Seoul National University, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Medical Research Council, Japan Society for the Promotion of Science, Queensland Brain Institute, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, School of Medicine, University of California, Irvine, National Institute for Physiological Sciences
Awards: G1136351547, Genetic markers of white matter integrity in schizophrenia: Relationship to clini, Function BIRN, Functional neuroimaging of reward and motivation deficits in schizophrenia, Unified multivariate data-driven solutions for static and dynamic brain connectivity, Mapping Abnormal Neurodevelopment in Schizophrenia, The Role of Stress-Immune-Connectome Disruption in Mechanisms of Chinese Early Schizophrenia Spectrum, G2689512631, Identity and Function of Selenoprotein Genes, Clinical Translational Research Center for Neurodevelopmental Disorders, Mining the Genomewide Scan: Genetic Profiles of Structural Loss in Schizophrenia, G3240074144, Harvard Clinical and Translational Science Center (UL1), Kynurenic Acid and Cognitive Abnormalities in Schizophrenia, Towards Multisystem-Brain Successful Aging in Schizophrenia Spectrum, Institute for Clinical and Translational Science, G3836237695, Informed Data-Driven Fusion of Behavior, Brain Function, and Genes, Stratifying Resilience and Depression Longitudinally (STRADL), Quantitative Behavioral and Imaging Phenotypes of Amotivation in Schizophrenia, Schizophrenia Biomarkers: Memory Genes and fMRI, G5067462658, G5192599444, Multimodal Imaging of Neuropsychiatric Disorders (MIND): Mechanisms &, Center for Functional Imaging Technologies, Amish Connectome Project on Mental Illness, Shared Neural Circuitry in Comorbid Schizophrenia and Nicotine Addiction, Biological Mechanisms of Enhanced Neuroplasticity in First-Episode Schizophrenia, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G620491733, ENRICH-2: Stress-Reactivity and Self-Regulation in Infants with Prenatal Alcohol Exposure, Longitudinal multi-modal neuroimaging of irritability in youth, Solar-Eclipse Computational Tools for Imaging Genetics, Quantitative Neuroimaging in Psychosis, Hybrid GPU/CPU Computing Resource to Support Connectomic and Genomics, Neuromorphometry in Schizophrenia by Computer Algorithm, Neurobiology of Selective Attention in Schizophrenia, The Neurobiology of Affective Dysfunction in Schizophrenia, Development of measurement technology for excitatory and inhibitory brain network dynamics using ultra high field 7T MRI., The Neurobiology of Stimulus Encoding in Schizophrenia, Neural Oscillatory Biomarkers for Genetics and Animal Models of Schizophrenia, Schizophrenia Data and Software Tool Federation using BIRN Infrastructure, Psychosis: A Convergent Neuroscience Perspective, Institute for Clinical and Translational Science, Multivariate methods for identifying multitask/multimodal brain imaging biomarkers, Multidisciplinary Schizophrenia Research Training, C0-Overall: Fetal Ethanol-induced behavior deficits: Mechanisms, diagnosis and Intervention, Bio-Informatics Research Network Coordinating Center (BIRN-CC)
OpenAlex ID: W2804287612