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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

2018; Elsevier BV; Volume: 84; Issue: 9 Linguagem: Inglês

10.1016/j.biopsych.2018.04.023

1873-2402

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 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 Nordbø Jørgensen, Trine Vik Lagerberg, Ingrid Melle, Lars T. Westlye, Oliver Gruber, Bernd Kraemer, Anja Richter, David Zilles‐Wegner, Vince D. Calhoun, Benedicto Crespo‐Facorro, Roberto Roiz‐Santiáñez, Diana Tordesillas‐Gutiérrez, Carmel Loughland, Vaughan J. Carr, Stanley V. Catts, Vanessa Cropley, Janice M. Fullerton, Melissa J. Green, Frans Henskens, Assen Jablensky, Rhoshel Lenroot, Bryan Mowry, Patricia T. Michie, Christos Pantelis, Yann Quidé, Ulrich Schall, Rodney J. Scott, Murray J. Cairns, Marc L. 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, Ayşenil Belger, Greg Brown, Judith M. Ford, Fabìo Macciardi, Daniel H. Mathalon, Daniel S. OʼLeary, Steven G. Potkin, Adrian Preda, James T. Voyvodic, Kelvin O. Lim, Sarah McEwen, Fude Yang, Yunlong Tan, Shuping Tan, Zhiren Wang, Fengmei Fan, Jing Chen, Hong Xiang, Shiyou Tang, Hua Guo, Ping Wan, Wei Dong, H. Jeremy Bockholt, Stefan Ehrlich, Rick P.F. Wolthusen, Margaret King, Jody M. Shoemaker, Scott R. Sponheim, Lieuwe de Haan, Laura Koenders, Marise W. J. Machielsen, Thérèse 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, Sinéad Kelly, Christopher D. Whelan, Erin W. Dickie, David Rotenberg, Aristotle N. Voineskos, Simone Ciufolini, Joaquim Raduà, Paola Dazzan, Robin M. Murray, Tiago Reis Marques, Andrew Simmons, Stefan Borgwardt, Laura Egloff, Fabienne Harrisberger, Anita Riecher‐Rössler, Renata Smieskova, Kathryn Alpert, Lei Wang, Erik G. Jönsson, Sanne Koops, Iris E. 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, В. Г. Каледа, Helena Fatouros‐Bergman, Lena Flyckt, Geraldo F. Busatto, Pedro G. P. Rosa, Maurício H. Serpa, Marcus V. Zanetti, Cyril Höschl, Antonín Škoch, Filip Španiel, David Tomeček, 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 Temmingh, Anne Uhlmann, Carlos López‐Jaramillo, Danai Dima, Mary 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 Červenka, Lilly Schwieler, Fredrik Piehl, Ingrid Agartz, Karin Collste, Pauliina Victorsson, Anna Malmqvist, Mikael Hedberg, Funda Orhan,

Advanced Neuroimaging Techniques and Applications

BackgroundThe 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.MethodsThe 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.ResultsCompared 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.ConclusionsThe 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.