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

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

University of California, Irvine
Imaging Genetics and Neuroinformatics Lab
Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) [Georgia State University
Imaging Genetics Center
Keck School of Medicine of USC
Janssen Research and Development
Orygen
National Centre of Excellence in Youth Mental Health
Centre for Youth Mental Health
Department of Psychiatry and Neuroscience
University of Amsterdam
Department of Psychology
Yale University
Olin Neuropsychiatric Research Center
Institute of Living/Hartford Hospital
Division of Cerebral Integration
Natl. Inst. for Physiological S.
Osaka University
Department of Psychiatry
Department of Neuropsychiatry
Graduate School of Medicine
Department of Psychiatry
University of New Mexico
The Mind Research Network
Institute of Clinical Medicine
University of Oslo
Department of Psychiatric Research
Diakonhjemmet Hospital
Karolinska Institutet
Department of Psychiatry
University of Minnesota School of Public Health
Department of Psychiatry and Brain Center Rudolf Magnus
Utrecht University
University of California, Los Angeles
Erasmus Medical College
Division of Mental Health and Addiction
Center for Translational Imaging and Precision Medicine
University of California San Diego
Department of Radiology
Department of Psychiatry
Department of Cognitive Science
Ruprecht-Karls-Universität Heidelberg
Center for Translational Research in Systems Neuroscience and Psychiatry
Georg-August-Universität Göttingen
Department of Psychiatry
Hospital Universitario Marques de Valdecilla
Centro Investigación Biomédica en Red de Salud Mental
Neuroimaging Unit
University of Cantabria
University of Newcastle, Australia
Hunter Medical Research Institute, Australia
Hunter New England Local Health District
Department of Psychiatry
Monash University
School of Psychiatry
Macquarie University, Australian School of Advanced Medicine
Discipline of Psychiatry
The University of Queensland
Melbourne Neuropsychiatry Centre
University of Melbourne
School of Medical Sciences
Neuroscience Research Australia
School of Medicine and Public Health
School of Psychiatry and Clinical Neurosciences
Universität Westaustralien

751 Zitate (Scopus)

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.

Originalsprache	Englisch
Zeitschrift	Biological Psychiatry
Jahrgang	84
Ausgabenummer	9
Seiten (von - bis)	644-654
Seitenumfang	11
ISSN	0006-3223
DOIs	https://doi.org/10.1016/j.biopsych.2018.04.023
Publikationsstatus	Veröffentlicht - 01.11.2018

Fördermittel

The ENIGMA project is in part supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Grant No. U54EB020403). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments for the various participating data contributors are listed in Supplement 1. Author contributions are as follows: protocol design, quality testing, and meta-analysis, TGMvE, EW, DPH, LS, and WJ; data collection, processing, analysis, and funding, TGMvE, EW, DPH, LS, WJ, DCG, GDP, NY, MF, RH, NO, HY, JRB, VPC, IA, BAM, WC, SMCdZ, HEHP, RSK, RAO, NEMvH, OAA, AMD, NTD, TPG, CBH, UKH, KNJ, TVL, IM, LTW, OG, BK, AR, DZ, VDC, BC-F, RR-S, MJC, VJC, SCa, JR, VLC, JMFu, MJG, FAH, AJ, RKL, CL, BJM, PTM, CP, YQ, PER, GC, US, RJS, MSe, PAT, CSW, TWW, DWM, EH, PK, LMB, REG, RCG, TDS, DHW, ABel, GGB, JMFo, FM, DHM, DSO, SGP, AP, JV, KOL, SM, FY, YT, STan, ZW, FF, JC, HX, STang, HG, PW, DW, HJB, SE, RPFW, MDK, JMSh, SRS, LDH, LK, MWM, TvA, DJV, FA, NB, PdR, MI, FP, GS, PJM, EP-C, JR, RSa, AC, GD, SKe, CDW, EWD, DR, ANV, SCi, PD, RM, TRM, ASi, SB, LE, FHa, AR-R, RSm, KIA, LW, EGJ, SKo, IECS, ABer, ABo, ADG, EN, ARM, JMSt, JSK, J-YY, DMC, CM, IL, AST, TA, VK, HF-B, LF, GFB, PGPR, MHS, MVZ, CH, ASk, FS, DT, SPH, AMM, HCW, SML, CK, VO-K, MSt, FMH, DJS, HST, AU, CL-J, DD, AM, JIF, BAG, NJ, PMT, and JAT; manuscript preparation, TGMvE, JAT, and PMT. All authors contributed edits and approved the contents of the manuscript. TGMvE has had a research contract with Otsuka Pharmaceutical. AP has served as a consultant for Boehringer Ingelheim. The remaining authors report no biomedical financial interests or potential conflicts of interest. The ENIGMA project is in part supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Grant No. U54EB020403). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments for the various participating data contributors are listed in Supplement 1 .

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen
SDG 10 – Weniger Ungleichheiten

Zugriff auf Dokument

10.1016/j.biopsych.2018.04.023

Andere Dateien und Links

Link to publication in Scopus

Dieses zitieren

@article{b9e302b4316e4963b7a8845856d4632c,

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{\textendash}78 years; 66\% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10{\textendash}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.",

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 Cropley, \{Vanessa L.\} and Fullerton, \{Janice M.\} and Green, \{Melissa J.\} and Henskens, \{Frans A.\} and Assen Jablensky and Lenroot, \{Rhoshel K.\} and Stefan Borgwardt",

note = "Publisher Copyright: {\textcopyright} 2018 Society of Biological Psychiatry",

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 Inc.",

number = "9",

}

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.
in: Biological Psychiatry, Jahrgang 84, Nr. 9, 01.11.2018, S. 644-654.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

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 - Cropley, Vanessa L.

AU - Fullerton, Janice M.

AU - Green, Melissa J.

AU - Henskens, Frans A.

AU - Jablensky, Assen

AU - Lenroot, Rhoshel K.

AU - Borgwardt, Stefan

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.

UR - https://www.scopus.com/pages/publications/85049111550

U2 - 10.1016/j.biopsych.2018.04.023

DO - 10.1016/j.biopsych.2018.04.023

M3 - Journal articles

C2 - 29960671

AN - SCOPUS:85049111550

SN - 0006-3223

VL - 84

SP - 644

EP - 654

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 9

ER -

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

Abstract

Fördermittel

UN SDGs

Zugriff auf Dokument

Andere Dateien und Links

Fingerprint

Dieses zitieren