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

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 (E...

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Published in	Biological psychiatry (1969) Vol. 84; no. 9; pp. 644 - 654
Main Authors	Walton, Esther, Jiang, Wenhao, Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Bustillo, Juan R., de Zwarte, Sonja M.C., Hulshoff Pol, Hilleke E., Andreassen, Ole A., Dale, Anders M., Doan, Nhat Trung, Gurholt, Tiril P., Hartberg, Cecilie B., Jørgensen, Kjetil N., Melle, Ingrid, Westlye, Lars T., Gruber, Oliver, Kraemer, Bernd, Tordesillas-Gutiérrez, Diana, Fullerton, Janice M., Green, Melissa J., Henskens, Frans A., Quidé, Yann, Schall, Ulrich, Scott, Rodney J., Cairns, Murray J., Tooney, Paul A., Rasser, Paul E., Cooper, Gavin, Morris, Derek W., Hong, Elliot, Gur, Ruben C., Satterthwaite, Theodore D., Wolf, Daniel H., Mathalon, Daniel H., Potkin, Steven G., Preda, Adrian, Voyvodic, James, Lim, Kelvin O., McEwen, Sarah, Tan, Yunlong, Fan, Fengmei, Guo, Hua, Wan, Ping, Bockholt, Henry J., Ehrlich, Stefan, Wolthusen, Rick P.F., King, Margaret D., De Haan, Lieuwe, de Rossi, Pietro, Iorio, Mariangela, McKenna, Peter J., Pomarol-Clotet, Edith, Kelly, Sinead, Whelan, Christopher D., Voineskos, Aristotle N., Ciufolini, Simone, Radua, Joaquim, Dazzan, Paola, Murray, Robin, Reis Marques, Tiago, Simmons, Andrew, Egloff, Laura, Harrisberger, Fabienne, Riecher-Rössler, Anita, Alpert, Kathryn I., Koops, Sanne, Bertolino, Alessandro, Bonvino, Aurora, Di Giorgio, Annabella, Stephen, Julia M., Cannon, Dara M., McDonald, Colm, Lebedeva, Irina, Tomyshev, Alexander S., Akhadov, Tolibjohn, Farde, Lars, Flyckt, Lena, Erhardt, Sophie, Schwieler, Lilly, Agartz, Ingrid, Collste, Karin, Victorsson, Pauliina, Orhan, Funda, Busatto, Geraldo F., Rosa, Pedro G.P., Zanetti, Marcus V., Skoch, Antonin, Spaniel, Filip, Tomecek, David, Hagenaars, Saskia P., McIntosh, Andrew M., Oertel-Knöchel, Viola, Uhlmann, Anne, Lopez-Jaramillo, Carlos, McMahon, Agnes, Faskowitz, Joshua I., Thompson, Paul M., Turner, Jessica A.
Format	Journal Article
Language	English
Published	United States Elsevier Inc 01.11.2018 Elsevier Science
Subjects	Adolescent Adult Age of Onset Aged Brain - diagnostic imaging Brain - pathology Case-Control Studies Child Cortical Female Frontal Lobe - diagnostic imaging Frontal Lobe - pathology Humans Imaging Linear Models Magnetic Resonance Imaging Male Meta-analysis Middle Aged Neuroimaging Prefrontal Cortex - diagnostic imaging Prefrontal Cortex - pathology Schizophrenia Schizophrenia - diagnostic imaging Schizophrenia - pathology Severity of Illness Index Surface area Temporal Lobe - diagnostic imaging Temporal Lobe - pathology Thickness Young Adult Thickness Schizophrenia Surface area Cortical Imaging Meta-analysis
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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.
AbstractList	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. 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. 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. 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.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.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.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.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.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.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.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.
Author	Lebedeva, Irina Lenroot, Rhoshel K. Dickie, Erin W. Koops, Sanne O’Leary, Daniel S. Lawrie, Stephen M. Gutman, Boris A. Ehrlich, Stefan Ford, Judith M. Calhoun, Vince D. De Haan, Lieuwe Cropley, Vanessa L. Morris, Derek W. Scott, Rodney J. Radua, Joaquim Di Giorgio, Annabella Preda, Adrian Stein, Dan J. Rasser, Paul E. Rotenberg, David Dima, Danai Lim, Kelvin O. Kelly, Sinead Malmqvist, Anna Henskens, Frans A. Schwieler, Lilly Sponheim, Scott R. Mayer, Andrew R. Erhardt, Sophie Walton, Esther Tordesillas-Gutiérrez, Diana Oertel-Knöchel, Viola Turner, Jessica A. Catts, Stanley Mathalon, Daniel H. Murray, Robin Flyckt, Lena Roiz-Santiañez, Roberto Chen, Jingxu Beard, Lauren M. Borgwardt, Stefan Hagenaars, Saskia P. Voyvodic, James Bonvino, Aurora Banaj, Nerisa de Zwarte, Sonja M.C. Dazzan, Paola Voineskos, Aristotle N. Pearlson, Godfrey D. Riecher-Rössler, Anita Green, Melissa J. Shoemaker, Jody M. Ciufolini, Simone Akhadov, Tolibjohn McMahon, Agnes Cairns, Murray J. Fan, Fengmei Fatouros-Bergman, Helena Doan, Nhat Trung McDonald, Colm McKenna, P
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surname: Uhlmann fullname: Uhlmann, Anne organization: Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa – sequence: 185 givenname: Carlos surname: Lopez-Jaramillo fullname: Lopez-Jaramillo, Carlos organization: Research Group in Psychiatry, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia – sequence: 187 givenname: Agnes surname: McMahon fullname: McMahon, Agnes organization: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California – sequence: 188 givenname: Joshua I. surname: Faskowitz fullname: Faskowitz, Joshua I. organization: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California – sequence: 191 givenname: Paul M. surname: Thompson fullname: Thompson, Paul M. organization: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California – sequence: 192 givenname: Jessica A. surname: Turner fullname: Turner, Jessica A. organization: Imaging Genetics and Neuroinformatics Lab, Georgia State University, Atlanta, Georgia
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Snippet	The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies.... Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain...
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SubjectTerms	Adolescent Adult Age of Onset Aged Brain - diagnostic imaging Brain - pathology Case-Control Studies Child Cortical Female Frontal Lobe - diagnostic imaging Frontal Lobe - pathology Humans Imaging Linear Models Magnetic Resonance Imaging Male Meta-analysis Middle Aged Neuroimaging Prefrontal Cortex - diagnostic imaging Prefrontal Cortex - pathology Schizophrenia Schizophrenia - diagnostic imaging Schizophrenia - pathology Severity of Illness Index Surface area Temporal Lobe - diagnostic imaging Temporal Lobe - pathology Thickness Young Adult
Title	Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium
URI	https://www.clinicalkey.com/#!/content/1-s2.0-S0006322318315178 https://dx.doi.org/10.1016/j.biopsych.2018.04.023 https://www.ncbi.nlm.nih.gov/pubmed/29960671 https://www.proquest.com/docview/2063715543 http://hdl.handle.net/10852/66369 http://kipublications.ki.se/Default.aspx?queryparsed=id:139379219
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