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

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, Rene S. KahnRoel 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. Jorgensen, Trine Lagerberg, Ingrid Melle, Lars T. Westlye, Oliver Gruber, Bernd Kraemer, Anja Richter, David Zilles, Vince D. Calhoun, Benedicto Crespo-Facorro, Roberto Roiz-Santianez, Diana Tordesillas-Gutierrez, Carmel Loughland, Vaughan J. Carr, Stanley Catts, Vanessa L. Cropley, Janice M. Fullerton, Melissa J. Green, Frans A. Henskens, Assen Jablensky, Rhoshel K. Lenroot, Therese van Amelsvoort, Karolinska Schizophrenia Project Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)644-654
Number of pages11
JournalBiological Psychiatry
Issue number9
Publication statusPublished - 1 Nov 2018


  • Cortical
  • Imaging
  • Meta-analysis
  • Schizophrenia
  • Surface area
  • Thickness
  • MRI


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