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, René 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 Jørgensen, Trine V Lagerberg, Ingrid Melle, Lars T Westlye, Oliver Gruber, Bernd Kraemer, Anja Richter, David Zilles, Vince D Calhoun, Benedicto Crespo-Facorro, Roberto Roiz-Santiañez, Diana Tordesillas-Gutiérrez, Carmel Loughland, Vaughan J Carr, Stanley Catts, Vanessa L Cropley, Janice M Fullerton, Melissa J Green, Frans A Henskens, Assen Jablensky, Rhoshel K Lenroot, Bryan J Mowry

Research output: Contribution to journalArticle

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Abstract

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
Volume84
Issue number9
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

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

Cite this

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. / van Erp, Theo G M; Walton, Esther; Hibar, Derrek P; Schmaal, Lianne; Jiang, Wenhao; Glahn, David C; Pearlson, Godfrey D; Yao, Nailin; Fukunaga, Masaki; Hashimoto, Ryota; Okada, Naohiro; Yamamori, Hidenaga; Bustillo, Juan R; Clark, Vincent P; Agartz, Ingrid; Mueller, Bryon A; Cahn, Wiepke; de Zwarte, Sonja M C; Hulshoff Pol, Hilleke E; Kahn, René S; Ophoff, Roel A; van Haren, Neeltje E M; Andreassen, Ole A; Dale, Anders M; Doan, Nhat Trung; Gurholt, Tiril P; Hartberg, Cecilie B; Haukvik, Unn K; Jørgensen, Kjetil N; Lagerberg, Trine V; Melle, Ingrid; Westlye, Lars T; Gruber, Oliver; Kraemer, Bernd; Richter, Anja; Zilles, David; Calhoun, Vince D; Crespo-Facorro, Benedicto; Roiz-Santiañez, Roberto; Tordesillas-Gutiérrez, Diana; Loughland, Carmel; Carr, Vaughan J; Catts, Stanley; Cropley, Vanessa L; Fullerton, Janice M; Green, Melissa J; Henskens, Frans A; Jablensky, Assen; Lenroot, Rhoshel K; Mowry, Bryan J.

In: Biological Psychiatry, Vol. 84, No. 9, 01.11.2018, p. 644-654.

Research output: Contribution to journalArticle

van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Bustillo, JR, Clark, VP, Agartz, I, Mueller, BA, Cahn, W, de Zwarte, SMC, Hulshoff Pol, HE, Kahn, RS, Ophoff, RA, van Haren, NEM, Andreassen, OA, Dale, AM, Doan, NT, Gurholt, TP, Hartberg, CB, Haukvik, UK, Jørgensen, KN, Lagerberg, TV, Melle, I, Westlye, LT, Gruber, O, Kraemer, B, Richter, A, Zilles, D, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Carr, VJ, Catts, S, Cropley, VL, Fullerton, JM, Green, MJ, Henskens, FA, Jablensky, A, Lenroot, RK & Mowry, BJ 2018, 'Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium', Biological Psychiatry, vol. 84, no. 9, pp. 644-654. https://doi.org/10.1016/j.biopsych.2018.04.023
van Erp, Theo G M ; Walton, Esther ; Hibar, Derrek P ; Schmaal, Lianne ; Jiang, Wenhao ; Glahn, David C ; Pearlson, Godfrey D ; Yao, Nailin ; Fukunaga, Masaki ; Hashimoto, Ryota ; Okada, Naohiro ; Yamamori, Hidenaga ; Bustillo, Juan R ; Clark, Vincent P ; Agartz, Ingrid ; Mueller, Bryon A ; Cahn, Wiepke ; de Zwarte, Sonja M C ; Hulshoff Pol, Hilleke E ; Kahn, René S ; Ophoff, Roel A ; van Haren, Neeltje E M ; Andreassen, Ole A ; Dale, Anders M ; Doan, Nhat Trung ; Gurholt, Tiril P ; Hartberg, Cecilie B ; Haukvik, Unn K ; Jørgensen, Kjetil N ; Lagerberg, Trine V ; Melle, Ingrid ; Westlye, Lars T ; Gruber, Oliver ; Kraemer, Bernd ; Richter, Anja ; Zilles, David ; Calhoun, Vince D ; Crespo-Facorro, Benedicto ; Roiz-Santiañez, Roberto ; Tordesillas-Gutiérrez, Diana ; Loughland, Carmel ; Carr, Vaughan J ; Catts, Stanley ; Cropley, Vanessa L ; Fullerton, Janice M ; Green, Melissa J ; Henskens, Frans A ; Jablensky, Assen ; Lenroot, Rhoshel K ; Mowry, Bryan J. / Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. In: Biological Psychiatry. 2018 ; Vol. 84, No. 9. pp. 644-654.
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abstract = "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.",
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author = "{van Erp}, {Theo G M} and Esther Walton and Hibar, {Derrek P} and Lianne Schmaal and Wenhao Jiang and Glahn, {David C} and Pearlson, {Godfrey D} and Nailin Yao and Masaki Fukunaga and Ryota Hashimoto and Naohiro Okada and Hidenaga Yamamori and Bustillo, {Juan R} and Clark, {Vincent P} and Ingrid Agartz and Mueller, {Bryon A} and Wiepke Cahn and {de Zwarte}, {Sonja M C} and {Hulshoff Pol}, {Hilleke E} and Kahn, {Ren{\'e} S} and Ophoff, {Roel A} and {van Haren}, {Neeltje E M} and Andreassen, {Ole A} and Dale, {Anders M} and Doan, {Nhat Trung} and Gurholt, {Tiril P} and Hartberg, {Cecilie B} and Haukvik, {Unn K} and J{\o}rgensen, {Kjetil N} and Lagerberg, {Trine V} and Ingrid Melle and Westlye, {Lars T} and Oliver Gruber and Bernd Kraemer and Anja Richter and David Zilles and Calhoun, {Vince D} and Benedicto Crespo-Facorro and Roberto Roiz-Santia{\~n}ez and Diana Tordesillas-Guti{\'e}rrez and Carmel Loughland and Carr, {Vaughan J} and Stanley Catts and Cropley, {Vanessa L} and Fullerton, {Janice M} and Green, {Melissa J} and Henskens, {Frans A} and Assen Jablensky and Lenroot, {Rhoshel K} and Mowry, {Bryan J}",
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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 - 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 - Hulshoff Pol, Hilleke E

AU - Kahn, René S

AU - Ophoff, Roel A

AU - van Haren, Neeltje E M

AU - Andreassen, Ole A

AU - Dale, Anders M

AU - Doan, Nhat Trung

AU - Gurholt, Tiril P

AU - Hartberg, Cecilie B

AU - Haukvik, Unn K

AU - Jørgensen, Kjetil N

AU - Lagerberg, Trine V

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-Santiañez, Roberto

AU - Tordesillas-Gutiérrez, 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 - Lenroot, Rhoshel K

AU - Mowry, Bryan J

N1 - Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

U2 - 10.1016/j.biopsych.2018.04.023

DO - 10.1016/j.biopsych.2018.04.023

M3 - Article

VL - 84

SP - 644

EP - 654

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 9

ER -