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

Karolinska Schizophrenia Project; 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 Kahn; Roel 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; Simone Ciufolini; Joaquim Radua; Paola Dazzan; Robin Murray; Tiago Reis Marques; Andrew Simmons; Danai Dima

doi:10.1016/j.biopsych.2018.04.023

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

Karolinska Schizophrenia Project, 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 PolRené S Kahn, Roel 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, Simone Ciufolini, Joaquim Radua, Paola Dazzan, Robin Murray, Tiago Reis Marques, Andrew Simmons, Danai Dima

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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 language	English
Pages (from-to)	644-654
Number of pages	11
Journal	Biological psychiatry
Volume	84
Issue number	9
Early online date	14 May 2018
DOIs	https://doi.org/10.1016/j.biopsych.2018.04.023
Publication status	Published - 1 Nov 2018

Keywords

Adolescent
Adult
Age of Onset
Aged
Brain/diagnostic imaging
Case-Control Studies
Child
Female
Frontal Lobe/diagnostic imaging
Humans
Linear Models
Magnetic Resonance Imaging
Male
Middle Aged
Neuroimaging
Prefrontal Cortex/diagnostic imaging
Schizophrenia/diagnostic imaging
Severity of Illness Index
Temporal Lobe/diagnostic imaging
Young Adult

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Cite this

Karolinska Schizophrenia Project, van Erp, T. G. M., Walton, E., Hibar, D. P., Schmaal, L., Jiang, W., Glahn, D. C., Pearlson, G. D., Yao, N., Fukunaga, M., Hashimoto, R., Okada, N., Yamamori, H., Bustillo, J. R., Clark, V. P., Agartz, I., Mueller, B. A., Cahn, W., de Zwarte, S. M. C., ... Dima, D. (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, 84(9), 644-654. https://doi.org/10.1016/j.biopsych.2018.04.023

@article{bfa3190d4a8e47558a67f42335635074,

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

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.",

keywords = "Adolescent, Adult, Age of Onset, Aged, Brain/diagnostic imaging, Case-Control Studies, Child, Female, Frontal Lobe/diagnostic imaging, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Prefrontal Cortex/diagnostic imaging, Schizophrenia/diagnostic imaging, Severity of Illness Index, Temporal Lobe/diagnostic imaging, Young Adult",

author = "{Karolinska Schizophrenia Project} and {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 Simone Ciufolini and Joaquim Radua and Paola Dazzan and Robin Murray and {Reis Marques}, Tiago and Andrew Simmons and Danai Dima",

year = "2018",

month = nov,

day = "1",

doi = "10.1016/j.biopsych.2018.04.023",

language = "English",

volume = "84",

pages = "644--654",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

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Karolinska Schizophrenia Project, 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, Ciufolini, S , Radua, J , Dazzan, P , Murray, R , Reis Marques, T , Simmons, A & Dima, D 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

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. / Karolinska Schizophrenia Project; van Erp, Theo G M; Walton, Esther et al.
In: Biological psychiatry, Vol. 84, No. 9, 01.11.2018, p. 644-654.

Research output: Contribution to journal › Article › peer-review

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 - 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 - Ciufolini, Simone

AU - Radua, Joaquim

AU - Dazzan, Paola

AU - Murray, Robin

AU - Reis Marques, Tiago

AU - Simmons, Andrew

AU - Dima, Danai

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 - Adolescent

KW - Adult

KW - Age of Onset

KW - Aged

KW - Brain/diagnostic imaging

KW - Case-Control Studies

KW - Child

KW - Female

KW - Frontal Lobe/diagnostic imaging

KW - Humans

KW - Linear Models

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Neuroimaging

KW - Prefrontal Cortex/diagnostic imaging

KW - Schizophrenia/diagnostic imaging

KW - Severity of Illness Index

KW - Temporal Lobe/diagnostic imaging

KW - Young Adult

U2 - 10.1016/j.biopsych.2018.04.023

DO - 10.1016/j.biopsych.2018.04.023

M3 - Article

C2 - 29960671

SN - 0006-3223

VL - 84

SP - 644

EP - 654

JO - Biological psychiatry

JF - Biological psychiatry

IS - 9

ER -

Karolinska Schizophrenia Project, van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W et al. 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. 2018 Nov 1;84(9):644-654. Epub 2018 May 14. doi: 10.1016/j.biopsych.2018.04.023

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

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Keywords

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