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Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 controls via the ENIGMA consortium

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Theo GM. 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 MC. de Zwarte, Hilleke E. Hulshoff Pol, René S. Kahn & 31 more Roel A. Ophoff, Neeltje EM. 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, Marc Seal, Therese van Amelsvoort, Sinead Kelly, Simone Ciufolini, Joaquim Radua, Paola Dazzan, Robin Murray, Tiago Reis Marques, Andrew Simmons, Laura Egloff, Stefan Borgwardt, Lei Wang, Colm McDonald, Saskia P. Hagenaars, Danai Dima

Original languageEnglish
JournalBiological psychiatry
Early online date14 May 2018
Publication statusE-pub ahead of print - 14 May 2018


King's Authors


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, range: 11-78; 66% male) and 5098 healthy volunteers (mean age=32.8, range: 10-87; 53% male), assessed with standardized methods, at 39 centers worldwide.

Compared to 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: 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, the effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were 2 to 3 times larger in antipsychotic medicated 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.

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