TY - JOUR
T1 - Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium
AU - Karolinska Schizophrenia Project
AU - van Erp, Theo G. M.
AU - Walton, Esther
AU - Hibar, Derrek P.
AU - Schmaal, Lianne
AU - Jiang, Wenhao
AU - Glahn, David C.
AU - Pearlson, Godfrey D.
AU - Yao, Nailin
AU - Fukunaga, Masaki
AU - Hashimoto, Ryota
AU - Okada, Naohiro
AU - Yamamori, Hidenaga
AU - Bustillo, Juan R.
AU - Clark, Vincent P.
AU - Agartz, Ingrid
AU - Mueller, Bryon A.
AU - Cahn, Wiepke
AU - de Zwarte, Sonja M. C.
AU - Pol, Hilleke E. Hulshoff
AU - Kahn, Rene S.
AU - Ophoff, Roel A.
AU - van Haren, Neeltje E. M.
AU - Andreassen, Ole A.
AU - Dale, Anders M.
AU - Nhat Trung Doan, null
AU - Gurholt, Tiril P.
AU - Hartberg, Cecilie B.
AU - Haukvik, Unn K.
AU - Jorgensen, Kjetil N.
AU - Lagerberg, Trine
AU - Melle, Ingrid
AU - Westlye, Lars T.
AU - Gruber, Oliver
AU - Kraemer, Bernd
AU - Richter, Anja
AU - Zilles, David
AU - Calhoun, Vince D.
AU - Crespo-Facorro, Benedicto
AU - Roiz-Santianez, Roberto
AU - Tordesillas-Gutierrez, Diana
AU - Loughland, Carmel
AU - Carr, Vaughan J.
AU - Catts, Stanley
AU - Cropley, Vanessa L.
AU - Fullerton, Janice M.
AU - Green, Melissa J.
AU - Henskens, Frans A.
AU - Jablensky, Assen
AU - Sommer, Iris E. C.
AU - Wang, Lei
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - Cortical
KW - Imaging
KW - Meta-analysis
KW - Schizophrenia
KW - Surface area
KW - Thickness
KW - ULTRA-HIGH-RISK
KW - 1ST EPISODE SCHIZOPHRENIA
KW - 1ST-EPISODE PSYCHOSIS
KW - ANTIPSYCHOTIC TREATMENT
KW - ONSET SCHIZOPHRENIA
KW - CEREBRAL-CORTEX
KW - THICKNESS
KW - SYMPTOMS
KW - MRI
KW - VOLUMES
U2 - 10.1016/j.biopsych.2018.04.023
DO - 10.1016/j.biopsych.2018.04.023
M3 - Article
SN - 0006-3223
VL - 84
SP - 644
EP - 654
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 9
ER -