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3. 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?

Author

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, Vincent P. Clark, Bryon A. Mueller, Sonja M.C. de Zwarte, Roel A. Ophoff, Neeltje E.M. van Haren, Ole A. Andreassen, Tiril P. Gurholt, Oliver Gruber, Bernd Kraemer, Anja Richter, Vince D. Calhoun, Benedicto Crespo-Facorro, Roberto Roiz-Santiañez, Diana Tordesillas-Gutiérrez, Carmel Loughland, Stanley Catts, Janice M. Fullerton, Melissa J. Green, Frans Henskens, Assen Jablensky, Bryan J. Mowry, 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, Elliot Hong, Peter Kochunov, Raquel E. Gur, Ruben C. Gur, Judith M. Ford, Fabio Macciardi, Daniel H. Mathalon, Steven G. Potkin, Adrian Preda, Fengmei Fan, Stefan Ehrlich, Margaret D. King, Lieuwe De Haan, Dick J. Veltman, Francesca Assogna, Nerisa Banaj, Pietro de Rossi, Mariangela Iorio, Fabrizio Piras, Gianfranco Spalletta, Edith Pomarol-Clotet, Sinead Kelly, Simone Ciufolini, Joaquim Radua, Robin Murray, Tiago Reis Marques, Andrew Simmons, Stefan Borgwardt, Fabienne Schönborn-Harrisberger, Anita Riecher-Rössler, Renata Smieskova, Kathryn I. Alpert, Alessandro Bertolino, Aurora Bonvino, Annabella Di Giorgio, Emma Neilson, Andrew R. Mayer, Je-Yeon Yun, Dara M. Cannon, Irina Lebedeva, Alexander S. Tomyshev, Tolibjohn Akhadov, Vasily Kaleda, Helena Fatouros-Bergman, Lena Flyckt, Pedro G.P. Rosa, Mauricio H. Serpa, Marcus V. Zanetti, Cyril Hoschl, Antonin Skoch, Filip Spaniel, David Tomecek, Andrew M. McIntosh, Heather C. Whalley, Christian Knöchel, Viola Oertel-Knöchel, Fleur M. Howells, Dan J. Stein, Henk S. Temmingh, Anne Uhlmann, Carlos Lopez-Jaramillo, Danai Dima, Joshua I. Faskowitz, Boris A. Gutman, Neda Jahanshad, Paul M. Thompson, Jessica A. Turner, Lars Farde, Simon Cervenka, Ingrid Agartz, Karin Collste, Pauliina Victorsson, Göran Engberg, Sophie Erhardt, Lilly Schwieler, Anna Malmqvist, Mikael Hedberg, Funda Orhan, Fredrik Piehl, APH - Mental Health, Adult Psychiatry, Universidad de Cantabria, Child and Adolescent Psychiatry / Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, and Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, Schizophrenia (object-oriented programming), Prefrontal Cortex, BF, Neuroimaging, Mega, Severity of Illness Index, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Medical imaging, Humans, Medical physics, Disease process, Age of Onset, Child, Biological Psychiatry, Aged, Brain Diseases, medicine.diagnostic_test, Brain, Magnetic resonance imaging, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, 030104 developmental biology, Case-Control Studies, Linear Models, Schizophrenia, RC0321, Female, Biological psychiatry, Psychology, 030217 neurology & neurosurgery
Abstract

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.

Published
2018
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