Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Merel C. Postema; Daan van Rooij; Evdokia Anagnostou; Celso Arango; Guillaume Auzias; Marlene Behrmann; Geraldo Busatto Filho; Sara Calderoni; Rosa Calvo; Eileen Daly; Christine Deruelle; Adriana Di Martino; Ilan Dinstein; Fabio Luis S. Duran; Sarah Durston; Christine Ecker; Stefan Ehrlich; Damien Fair; Jennifer Fedor; Xin Feng; Jackie Fitzgerald; Dorothea L. Floris; Christine M. Freitag; Louise Gallagher; David C. Glahn; Ilaria Gori; Shlomi Haar; Liesbeth Hoekstra; Neda Jahanshad; Maria Jalbrzikowski; Joost Janssen; Joseph A. King; Xiang Zhen Kong; Luisa Lazaro; Jason P. Lerch; Beatriz Luna; Mauricio M. Martinho; Jane McGrath; Sarah E. Medland; Filippo Muratori; Clodagh M. Murphy; Declan G.M. Murphy; Kirsten O’Hearn; Bob Oranje; Mara Parellada; Olga Puig; Alessandra Retico; Pedro Rosa; Katya Rubia; Devon Shook; Margot J. Taylor; Michela Tosetti; Gregory L. Wallace; Fengfeng Zhou; Paul M. Thompson; Simon E. Fisher; Jan K. Buitelaar; Clyde Francks

doi:10.1038/s41467-019-13005-8

Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Merel C. Postema, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Geraldo Busatto Filho, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Adriana Di Martino, Ilan Dinstein, Fabio Luis S. Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Xin FengJackie Fitzgerald, Dorothea L. Floris, Christine M. Freitag, Louise Gallagher, David C. Glahn, Ilaria Gori, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Xiang Zhen Kong, Luisa Lazaro, Jason P. Lerch, Beatriz Luna, Mauricio M. Martinho, Jane McGrath, Sarah E. Medland, Filippo Muratori, Clodagh M. Murphy, Declan G.M. Murphy, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Olga Puig, Alessandra Retico, Pedro Rosa, Katya Rubia, Devon Shook, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks

Behavioral Neuroscience

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

74 Scopus citations

Abstract

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

Original language	English (US)
Article number	4958
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13005-8
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

Access to Document

10.1038/s41467-019-13005-8

Cite this

Postema, M. C., van Rooij, D., Anagnostou, E., Arango, C., Auzias, G., Behrmann, M., Filho, G. B., Calderoni, S., Calvo, R., Daly, E., Deruelle, C., Di Martino, A., Dinstein, I., Duran, F. L. S., Durston, S., Ecker, C., Ehrlich, S., Fair, D., Fedor, J., ... Francks, C. (2019). Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets. Nature communications, 10(1), [4958]. https://doi.org/10.1038/s41467-019-13005-8

Postema, MC, van Rooij, D, Anagnostou, E, Arango, C, Auzias, G, Behrmann, M, Filho, GB, Calderoni, S, Calvo, R, Daly, E, Deruelle, C, Di Martino, A, Dinstein, I, Duran, FLS, Durston, S, Ecker, C, Ehrlich, S, Fair, D, Fedor, J, Feng, X, Fitzgerald, J, Floris, DL, Freitag, CM, Gallagher, L, Glahn, DC, Gori, I, Haar, S, Hoekstra, L, Jahanshad, N, Jalbrzikowski, M, Janssen, J, King, JA, Kong, XZ, Lazaro, L, Lerch, JP, Luna, B, Martinho, MM, McGrath, J, Medland, SE, Muratori, F, Murphy, CM, Murphy, DGM, O’Hearn, K, Oranje, B, Parellada, M, Puig, O, Retico, A, Rosa, P, Rubia, K, Shook, D, Taylor, MJ, Tosetti, M, Wallace, GL, Zhou, F, Thompson, PM, Fisher, SE, Buitelaar, JK & Francks, C 2019, 'Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets', Nature communications, vol. 10, no. 1, 4958. https://doi.org/10.1038/s41467-019-13005-8

@article{34852efedfb844a1a27818c73a86d8b9,

title = "Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets",

abstract = "Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen{\textquoteright}s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.",

author = "Postema, {Merel C.} and {van Rooij}, Daan and Evdokia Anagnostou and Celso Arango and Guillaume Auzias and Marlene Behrmann and Filho, {Geraldo Busatto} and Sara Calderoni and Rosa Calvo and Eileen Daly and Christine Deruelle and {Di Martino}, Adriana and Ilan Dinstein and Duran, {Fabio Luis S.} and Sarah Durston and Christine Ecker and Stefan Ehrlich and Damien Fair and Jennifer Fedor and Xin Feng and Jackie Fitzgerald and Floris, {Dorothea L.} and Freitag, {Christine M.} and Louise Gallagher and Glahn, {David C.} and Ilaria Gori and Shlomi Haar and Liesbeth Hoekstra and Neda Jahanshad and Maria Jalbrzikowski and Joost Janssen and King, {Joseph A.} and Kong, {Xiang Zhen} and Luisa Lazaro and Lerch, {Jason P.} and Beatriz Luna and Martinho, {Mauricio M.} and Jane McGrath and Medland, {Sarah E.} and Filippo Muratori and Murphy, {Clodagh M.} and Murphy, {Declan G.M.} and Kirsten O{\textquoteright}Hearn and Bob Oranje and Mara Parellada and Olga Puig and Alessandra Retico and Pedro Rosa and Katya Rubia and Devon Shook and Taylor, {Margot J.} and Michela Tosetti and Wallace, {Gregory L.} and Fengfeng Zhou and Thompson, {Paul M.} and Fisher, {Simon E.} and Buitelaar, {Jan K.} and Clyde Francks",

note = "Funding Information: We thank the participants of all studies who have contributed data to the ENIGMA-ASD working group (http://enigma.ini.usc.edu/ongoing/enigma-asd-working-group/)14. This research was funded by the Max Planck Society (Germany). This study was further supported by the ENIGMA Center for Worldwide Medicine, Imaging & Genomics grant (NIH U54 EB020403) to Paul Thompson, and further supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115300 (EU-AIMS) and 777394 (AIMS-2-TRIALS), resources of which are composed of financial contribution from the European Union{\textquoteright}s Seventh Framework Programme and Horizon2020 programs and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies{\textquoteright} in-kind contribution. The Canadian samples were collected as part of the POND network funded by the Ontario Brain Institute (grant IDS-I l-02 to Anagnostou / Lerch). Thanks to Derrek Hibar for helping to generate Fig. 1. Funding Information: Dr. Anagnostou has served as a consultant or advisory board member for Roche and Takeda; she has received funding from the Alva Foundation, Autism Speaks, Brain Canada, the Canadian Institutes of Health Research, the Department of Defense, the National Centers of Excellence, NIH, the Ontario Brain Institute, the Physicians{\textquoteright} Services Incorporated (PSI) Foundation, Sanofi-Aventis, and SynapDx, as well as in-kind research support from AMO Pharma; she receives royalties from American Psychiatric Press and Springer and an editorial honorarium from Wiley. Her contribution is on behalf of the POND network. Dr. Arango has served as a consultant for or received honoraria or grants from Acadia, Abbott, Amgen, CIBERSAM, Fundaci{\'o}n Alicia Koplowitz, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Merck, Instituto de Salud Carlos III (cofinanced by the European Regional Development Fund “A way of making Europe,” CIBERSAM, the Madrid Regional Government [S2010/BMD-2422 AGES], the European Union Structural Funds, and the European Union Seventh Framework Programmeunder grant agreements FP7-HEALTH-2009-2.2.1-2-241909, FP7-HEALTH-2009-2.2.1-3- 242114, FP7-HEALTH-2013-2.2.1-2-603196, and FP7-HEALTH-2013-2.2.1-2-602478), Otsuka, Pfizer, Roche, Servier, Shire, Takeda, and Schering-Plough. Dr. Freitag has served as a consultant for Desitin regarding issues on ASD. Dr. Di Martino is a coauthor of the Italian version of the Social Responsiveness Scale, for which she may receive royalties. Her contribution is on behalf of the ABIDE and ABIDEII consortia. Dr. Rubia has received speaking honoraria from Eli Lilly, Medice, and Shire, and a grant from Shire for another project. Dr. Thompson received partial research support from Biogen, Inc. (Boston), for research unrelated to the topic of this manuscript. Dr. Buitelaar has served as a consultant, advisory board member, or speaker for Eli Lilly, Janssen-Cilag, Lundbeck, Medice, Novartis, Servier, Shire, and Roche, and he has received research support from Roche and Vifor. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13005-8",

language = "English (US)",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

AU - Postema, Merel C.

AU - van Rooij, Daan

AU - Anagnostou, Evdokia

AU - Arango, Celso

AU - Auzias, Guillaume

AU - Behrmann, Marlene

AU - Filho, Geraldo Busatto

AU - Calderoni, Sara

AU - Calvo, Rosa

AU - Daly, Eileen

AU - Deruelle, Christine

AU - Di Martino, Adriana

AU - Dinstein, Ilan

AU - Duran, Fabio Luis S.

AU - Durston, Sarah

AU - Ecker, Christine

AU - Ehrlich, Stefan

AU - Fair, Damien

AU - Fedor, Jennifer

AU - Feng, Xin

AU - Fitzgerald, Jackie

AU - Floris, Dorothea L.

AU - Freitag, Christine M.

AU - Gallagher, Louise

AU - Glahn, David C.

AU - Gori, Ilaria

AU - Haar, Shlomi

AU - Hoekstra, Liesbeth

AU - Jahanshad, Neda

AU - Jalbrzikowski, Maria

AU - Janssen, Joost

AU - King, Joseph A.

AU - Kong, Xiang Zhen

AU - Lazaro, Luisa

AU - Lerch, Jason P.

AU - Luna, Beatriz

AU - Martinho, Mauricio M.

AU - McGrath, Jane

AU - Medland, Sarah E.

AU - Muratori, Filippo

AU - Murphy, Clodagh M.

AU - Murphy, Declan G.M.

AU - O’Hearn, Kirsten

AU - Oranje, Bob

AU - Parellada, Mara

AU - Puig, Olga

AU - Retico, Alessandra

AU - Rosa, Pedro

AU - Rubia, Katya

AU - Shook, Devon

AU - Taylor, Margot J.

AU - Tosetti, Michela

AU - Wallace, Gregory L.

AU - Zhou, Fengfeng

AU - Thompson, Paul M.

AU - Fisher, Simon E.

AU - Buitelaar, Jan K.

AU - Francks, Clyde

N1 - Funding Information: We thank the participants of all studies who have contributed data to the ENIGMA-ASD working group (http://enigma.ini.usc.edu/ongoing/enigma-asd-working-group/)14. This research was funded by the Max Planck Society (Germany). This study was further supported by the ENIGMA Center for Worldwide Medicine, Imaging & Genomics grant (NIH U54 EB020403) to Paul Thompson, and further supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115300 (EU-AIMS) and 777394 (AIMS-2-TRIALS), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme and Horizon2020 programs and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in-kind contribution. The Canadian samples were collected as part of the POND network funded by the Ontario Brain Institute (grant IDS-I l-02 to Anagnostou / Lerch). Thanks to Derrek Hibar for helping to generate Fig. 1. Funding Information: Dr. Anagnostou has served as a consultant or advisory board member for Roche and Takeda; she has received funding from the Alva Foundation, Autism Speaks, Brain Canada, the Canadian Institutes of Health Research, the Department of Defense, the National Centers of Excellence, NIH, the Ontario Brain Institute, the Physicians’ Services Incorporated (PSI) Foundation, Sanofi-Aventis, and SynapDx, as well as in-kind research support from AMO Pharma; she receives royalties from American Psychiatric Press and Springer and an editorial honorarium from Wiley. Her contribution is on behalf of the POND network. Dr. Arango has served as a consultant for or received honoraria or grants from Acadia, Abbott, Amgen, CIBERSAM, Fundación Alicia Koplowitz, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Merck, Instituto de Salud Carlos III (cofinanced by the European Regional Development Fund “A way of making Europe,” CIBERSAM, the Madrid Regional Government [S2010/BMD-2422 AGES], the European Union Structural Funds, and the European Union Seventh Framework Programmeunder grant agreements FP7-HEALTH-2009-2.2.1-2-241909, FP7-HEALTH-2009-2.2.1-3- 242114, FP7-HEALTH-2013-2.2.1-2-603196, and FP7-HEALTH-2013-2.2.1-2-602478), Otsuka, Pfizer, Roche, Servier, Shire, Takeda, and Schering-Plough. Dr. Freitag has served as a consultant for Desitin regarding issues on ASD. Dr. Di Martino is a coauthor of the Italian version of the Social Responsiveness Scale, for which she may receive royalties. Her contribution is on behalf of the ABIDE and ABIDEII consortia. Dr. Rubia has received speaking honoraria from Eli Lilly, Medice, and Shire, and a grant from Shire for another project. Dr. Thompson received partial research support from Biogen, Inc. (Boston), for research unrelated to the topic of this manuscript. Dr. Buitelaar has served as a consultant, advisory board member, or speaker for Eli Lilly, Janssen-Cilag, Lundbeck, Medice, Novartis, Servier, Shire, and Roche, and he has received research support from Roche and Vifor. The remaining authors declare no competing interests. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

AB - Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

UR - http://www.scopus.com/inward/record.url?scp=85074287980&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074287980&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-13005-8

DO - 10.1038/s41467-019-13005-8

M3 - Article

C2 - 31673008

AN - SCOPUS:85074287980

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4958

ER -

Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this