Greater male than female variability in regional brain structure across the lifespan

Karolinska Schizophrenia Project (KaSP) consortium

doi:10.1002/hbm.25204

Greater male than female variability in regional brain structure across the lifespan

Karolinska Schizophrenia Project (KaSP) consortium

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Original language	English
Pages (from-to)	470-499
Number of pages	30
Journal	Human Brain Mapping
Volume	43
Issue number	1
Early online date	12 Oct 2020
DOIs	https://doi.org/10.1002/hbm.25204 https://doi.org/10.1101/2020.02.17.952010
Publication status	Published - Jan 2022

Bibliographical note

Funding Information:
The authors declare the following competing interests: OAA: Speaker's honorarium from Lundbeck, Consultant of HealthLyti; PA: Received payments for consultancy to Shire/Takeda, Medic, educational/research awards from Shire/Takeda, GW Pharma, Janssen‐Cila, speaker at sponsored events for Shire, Flynn Pharma, Medic; TB: advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm, conference support or speaker's fee by Lilly, Medice, and Shire, received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press ‐ the present work is unrelated to the above grants and relationship; DB: serves as an unpaid scientific consultant for an EU‐funded neurofeedback trial that is unrelated to the present work; HB: Advisory Board, Nutricia Australi; CRKC: received partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript; BF: received educational speaking fees from Medice; HJG: received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care; NJ and PMT: MPI of a research related grant from Biogen, Inc., for research unrelated to the contents of this manuscript; JK: given talks at educational events sponsored by Medic; all funds are received by King's College London and used for studies of ADHD; DM‐C: receives fees from UpToDate, Inc and Elsevier, all unrelated to the current work; AMM: received research support from Eli Lilly, Janssen, and the Sackler Foundation, and speaker fees from Illumina and Janssen; DJS: received research grants and/or honoraria from Lundbeck and Sun. The remaining authors declare no competing interests.

Funding Information:
BIG ‐ Nijmegen 1.5T; Deutsche Forschungsgemeinschaft, Grant/Award Numbers: KFO 125, TRR 58/A1, TRR 58/A5, SFB‐TRR 58/B01, SFB‐TRR 58/B06; Deutsche Forschungsgesellschaft collaborative research center, Grant/Award Number: 636; EU H2020, Grant/Award Number: #667302; European Community's Horizon 2020 Programme, Grant/Award Numbers: 643051, 667302; European Community's Seventh Framework Programme, Grant/Award Numbers: 602805, 603016, 602450, 278948; European Research Council, Grant/Award Numbers: ERC‐2010‐StG‐263234, ERC‐230374; German Research Foundation, Grant/Award Number: KFO 125; KA Wallenberg Foundation; KNAW Academy Professor Award, Grant/Award Number: PAH/6635; Miguel Servet Research Contract, Grant/Award Number: CPII16/0020; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: 51.02.061 to H.H., NWO 51.02.062 to D.B., NWO‐ NIH; Netherlands Brain Foundation grant, Grant/Award Number: 2010(1)‐50; NIA, Grant/Award Number: T32AG058507; NIH/NIMH, Grant/Award Numbers: 5T32MH073526, U54EB020403, U54 EB020403, R56 AG058; NIHR Biomedical Research Centre for Mental Health, Grant/Award Number: NIHR/MRC (14/23/17); NIHR senior investigator award, Grant/Award Number: NF‐SI‐0616‐10040; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433‐09‐ 229; Research Council of Norway, Grant/Award Numbers: #223273, #288083, #230345; South London and Maudsley Trust, Grant/Award Number: 064846; South‐Eastern Norway Regional Health Authority, Grant/Award Numbers: #2017112, #2019069; the Generalitat de Catalunya, Grant/Award Number: 2017SGR01343; the German Research Foundation, Grant/Award Numbers: WA 1539/4‐1, SCHN 1205/3‐1; The Marató TV3 Foundation, Grant/Award Numbers: #091710, #091710; UK Medical Research Council Grant, Grant/Award Number: G03001896 to J Kuntsi; Vici Innovation Program, Grant/Award Numbers: 016‐130‐669, 91619115; National Institute of Aging, Grant/Award Number: R03AG064001; National Institute of General Medical Sciences, Grant/Award Number: P20GM130447 Funding information

Publisher Copyright:
© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

Funding

The authors declare the following competing interests: OAA: Speaker's honorarium from Lundbeck, Consultant of HealthLyti; PA: Received payments for consultancy to Shire/Takeda, Medic, educational/research awards from Shire/Takeda, GW Pharma, Janssen‐Cila, speaker at sponsored events for Shire, Flynn Pharma, Medic; TB: advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm, conference support or speaker's fee by Lilly, Medice, and Shire, received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press ‐ the present work is unrelated to the above grants and relationship; DB: serves as an unpaid scientific consultant for an EU‐funded neurofeedback trial that is unrelated to the present work; HB: Advisory Board, Nutricia Australi; CRKC: received partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript; BF: received educational speaking fees from Medice; HJG: received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care; NJ and PMT: MPI of a research related grant from Biogen, Inc., for research unrelated to the contents of this manuscript; JK: given talks at educational events sponsored by Medic; all funds are received by King's College London and used for studies of ADHD; DM‐C: receives fees from UpToDate, Inc and Elsevier, all unrelated to the current work; AMM: received research support from Eli Lilly, Janssen, and the Sackler Foundation, and speaker fees from Illumina and Janssen; DJS: received research grants and/or honoraria from Lundbeck and Sun. The remaining authors declare no competing interests. BIG ‐ Nijmegen 1.5T; Deutsche Forschungsgemeinschaft, Grant/Award Numbers: KFO 125, TRR 58/A1, TRR 58/A5, SFB‐TRR 58/B01, SFB‐TRR 58/B06; Deutsche Forschungsgesellschaft collaborative research center, Grant/Award Number: 636; EU H2020, Grant/Award Number: #667302; European Community's Horizon 2020 Programme, Grant/Award Numbers: 643051, 667302; European Community's Seventh Framework Programme, Grant/Award Numbers: 602805, 603016, 602450, 278948; European Research Council, Grant/Award Numbers: ERC‐2010‐StG‐263234, ERC‐230374; German Research Foundation, Grant/Award Number: KFO 125; KA Wallenberg Foundation; KNAW Academy Professor Award, Grant/Award Number: PAH/6635; Miguel Servet Research Contract, Grant/Award Number: CPII16/0020; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: 51.02.061 to H.H., NWO 51.02.062 to D.B., NWO‐ NIH; Netherlands Brain Foundation grant, Grant/Award Number: 2010(1)‐50; NIA, Grant/Award Number: T32AG058507; NIH/NIMH, Grant/Award Numbers: 5T32MH073526, U54EB020403, U54 EB020403, R56 AG058; NIHR Biomedical Research Centre for Mental Health, Grant/Award Number: NIHR/MRC (14/23/17); NIHR senior investigator award, Grant/Award Number: NF‐SI‐0616‐10040; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433‐09‐ 229; Research Council of Norway, Grant/Award Numbers: #223273, #288083, #230345; South London and Maudsley Trust, Grant/Award Number: 064846; South‐Eastern Norway Regional Health Authority, Grant/Award Numbers: #2017112, #2019069; the Generalitat de Catalunya, Grant/Award Number: 2017SGR01343; the German Research Foundation, Grant/Award Numbers: WA 1539/4‐1, SCHN 1205/3‐1; The Marató TV3 Foundation, Grant/Award Numbers: #091710, #091710; UK Medical Research Council Grant, Grant/Award Number: G03001896 to J Kuntsi; Vici Innovation Program, Grant/Award Numbers: 016‐130‐669, 91619115; National Institute of Aging, Grant/Award Number: R03AG064001; National Institute of General Medical Sciences, Grant/Award Number: P20GM130447 Funding information

Funders	Funder number
Advisory board
Biogen, Inc.
EU H2020
KA Wallenberg Foundation
NIH/NIMH
NIHR Biomedical Research Centre for Mental Health
NIHR/MRC	14/23/17
NWO‐ NIH
Netherlands Brain Foundation
Nutricia Australi
Sackler Foundation
South‐Eastern Norway Regional Health Authority
National Institute of Mental Health	5T32MH073526, R56 AG058, U54EB020403
National Institute on Aging	R03AG064001, T32AG058507
National Institute of General Medical Sciences	P20GM130447
National Institute of Biomedical Imaging and Bioengineering	R01EB006841
Eli Lilly and Company
Janssen Biotech
Biogen
Shire
Fundació la Marató de TV3	091710
South London and Maudsley NHS Foundation Trust	064846
Horizon 2020 Framework Programme	667302, 643051
H2020 European Research Council	ERC-2010-StG-263234, ERC-230374
Fresenius Medical Care North America
Medical Research Council	016‐130‐669, 91619115, G03001896
National Institute for Health Research	433‐09‐ 229, NF‐SI‐0616‐10040
King's College London
European Research Council	ERC‐230374, ERC‐2010‐StG‐263234
Deutsche Forschungsgemeinschaft	SFB‐TRR 58/B01, TRR 58/A1, KFO 125, TRR 58/A5, 636
Koninklijke Nederlandse Akademie van Wetenschappen	CPII16/0020, PAH/6635
Generalitat de Catalunya	WA 1539/4‐1, 2017SGR01343, SCHN 1205/3‐1
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	51.02.062, 51.02.061
Seventh Framework Programme	602805, 602450, 278948, 603016
Norges forskningsråd	223273, 230345, 288083
Helse Sør-Øst RHF	2019069, 2017112
H. Lundbeck A/S

Cohort Studies

Netherlands Twin Register (NTR)

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https://www.biorxiv.org/content/10.1101/2020.02.17.952010v6

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Cite this

@article{b7ab09dcfd684f65a602435380e5208b,

title = "Greater male than female variability in regional brain structure across the lifespan",

abstract = "For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.",

author = "Wierenga, {Lara M.} and Doucet, {Gaelle E.} and Danai Dima and Ingrid Agartz and Moji Aghajani and Akudjedu, {Theophilus N.} and Anton Albajes-Eizagirre and Dag Aln{\ae}s and Alpert, {Kathryn I.} and Andreassen, {Ole A.} and Alan Anticevic and Philip Asherson and Tobias Banaschewski and Nuria Bargallo and Sarah Baumeister and Ramona Baur-Streubel and Alessandro Bertolino and Aurora Bonvino and Boomsma, {Dorret I.} and Stefan Borgwardt and Josiane Bourque and {den Braber}, Anouk and Daniel Brandeis and Alan Breier and Henry Brodaty and Brouwer, {Rachel M.} and Buitelaar, {Jan K.} and Busatto, {Geraldo F.} and Calhoun, {Vince D.} and Canales-Rodr{\'i}guez, {Erick J.} and Cannon, {Dara M.} and Xavier Caseras and Castellanos, {Francisco X.} and Chaim-Avancini, {Tiffany M.} and Ching, {Christopher R.K.} and Clark, {Vincent P.} and Conrod, {Patricia J.} and Annette Conzelmann and Fabrice Crivello and Davey, {Christopher G.} and Dickie, {Erin W.} and Stefan Ehrlich and {van't Ent}, Dennis and Fisher, {Simon E.} and Fouche, {Jean Paul} and Barbara Franke and Paola Fuentes-Claramonte and {de Geus}, {Eco J.C.} and {Di Giorgio}, Annabella and Glahn, {David C.} and Gotlib, {Ian H.} and Grabe, {Hans J.} and Oliver Gruber and Patricia Gruner and Gur, {Raquel E.} and Gur, {Ruben C.} and Gurholt, {Tiril P.} and {de Haan}, Lieuwe and Beathe Haatveit and Harrison, {Ben J.} and Hartman, {Catharina A.} and Hatton, {Sean N.} and Heslenfeld, {Dirk J.} and {van den Heuvel}, {Odile A.} and Hickie, {Ian B.} and Hoekstra, {Pieter J.} and Sarah Hohmann and Holmes, {Avram J.} and Martine Hoogman and Norbert Hosten and Howells, {Fleur M.} and {Hulshoff Pol}, {Hilleke E.} and Chaim Huyser and Neda Jahanshad and James, {Anthony C.} and Jiyang Jiang and J{\"o}nsson, {Erik G.} and Joska, {John A.} and Kalnin, {Andrew J.} and Marieke Klein and Laura Koenders and Kolsk{\aa}r, {Knut K.} and Bernd Kr{\"a}mer and Jonna Kuntsi and Jim Lagopoulos and Luisa Lazaro and Lebedeva, {Irina S.} and Lee, {Phil H.} and Christine Lochner and Machielsen, {Marise W.J.} and Sophie Maingault and Martin, {Nicholas G.} and Ignacio Mart{\'i}nez-Zalaca{\'i}n and David Mataix-Cols and Bernard Mazoyer and McDonald, {Brenna C.} and Colm McDonald and McIntosh, {Andrew M.} and McMahon, {Katie L.} and Genevieve McPhilemy and {van der Meer}, Dennis and Mench{\'o}n, {Jos{\'e} M.} and Jilly Naaijen and Lars Nyberg and Jaap Oosterlaan and Yannis Paloyelis and Paul Pauli and Giulio Pergola and Edith Pomarol-Clotet and Portella, {Maria J.} and Joaquim Radua and Andreas Reif and Genevi{\`e}ve Richard and Roffman, {Joshua L.} and Rosa, {Pedro G.P.} and Sacchet, {Matthew D.} and Sachdev, {Perminder S.} and Raymond Salvador and Salvador Sarr{\'o} and Satterthwaite, {Theodore D.} and Saykin, {Andrew J.} and Serpa, {Mauricio H.} and Kang Sim and Andrew Simmons and Smoller, {Jordan W.} and Sommer, {Iris E.} and Carles Soriano-Mas and Stein, {Dan J.} and Strike, {Lachlan T.} and Szeszko, {Philip R.} and Temmingh, {Henk S.} and Thomopoulos, {Sophia I.} and Tomyshev, {Alexander S.} and Trollor, {Julian N.} and Anne Uhlmann and Veer, {Ilya M.} and Veltman, {Dick J.} and Aristotle Voineskos and Henry V{\"o}lzke and Henrik Walter and Lei Wang and Yang Wang and Bernd Weber and Wei Wen and West, {John D.} and Westlye, {Lars T.} and Whalley, {Heather C.} and Williams, {Steven C.R.} and Katharina Wittfeld and Wolf, {Daniel H.} and Wright, {Margaret J.} and Yoncheva, {Yuliya N.} and Zanetti, {Marcus V.} and Ziegler, {Georg C.} and {de Zubicaray}, {Greig I.} and Thompson, {Paul M.} and Crone, {Eveline A.} and Sophia Frangou and Tamnes, {Christian K.} and {Karolinska Schizophrenia Project (KaSP) consortium}",

note = "Funding Information: The authors declare the following competing interests: OAA: Speaker's honorarium from Lundbeck, Consultant of HealthLyti; PA: Received payments for consultancy to Shire/Takeda, Medic, educational/research awards from Shire/Takeda, GW Pharma, Janssen‐Cila, speaker at sponsored events for Shire, Flynn Pharma, Medic; TB: advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm, conference support or speaker's fee by Lilly, Medice, and Shire, received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press ‐ the present work is unrelated to the above grants and relationship; DB: serves as an unpaid scientific consultant for an EU‐funded neurofeedback trial that is unrelated to the present work; HB: Advisory Board, Nutricia Australi; CRKC: received partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript; BF: received educational speaking fees from Medice; HJG: received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care; NJ and PMT: MPI of a research related grant from Biogen, Inc., for research unrelated to the contents of this manuscript; JK: given talks at educational events sponsored by Medic; all funds are received by King's College London and used for studies of ADHD; DM‐C: receives fees from UpToDate, Inc and Elsevier, all unrelated to the current work; AMM: received research support from Eli Lilly, Janssen, and the Sackler Foundation, and speaker fees from Illumina and Janssen; DJS: received research grants and/or honoraria from Lundbeck and Sun. The remaining authors declare no competing interests. Funding Information: BIG ‐ Nijmegen 1.5T; Deutsche Forschungsgemeinschaft, Grant/Award Numbers: KFO 125, TRR 58/A1, TRR 58/A5, SFB‐TRR 58/B01, SFB‐TRR 58/B06; Deutsche Forschungsgesellschaft collaborative research center, Grant/Award Number: 636; EU H2020, Grant/Award Number: #667302; European Community's Horizon 2020 Programme, Grant/Award Numbers: 643051, 667302; European Community's Seventh Framework Programme, Grant/Award Numbers: 602805, 603016, 602450, 278948; European Research Council, Grant/Award Numbers: ERC‐2010‐StG‐263234, ERC‐230374; German Research Foundation, Grant/Award Number: KFO 125; KA Wallenberg Foundation; KNAW Academy Professor Award, Grant/Award Number: PAH/6635; Miguel Servet Research Contract, Grant/Award Number: CPII16/0020; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: 51.02.061 to H.H., NWO 51.02.062 to D.B., NWO‐ NIH; Netherlands Brain Foundation grant, Grant/Award Number: 2010(1)‐50; NIA, Grant/Award Number: T32AG058507; NIH/NIMH, Grant/Award Numbers: 5T32MH073526, U54EB020403, U54 EB020403, R56 AG058; NIHR Biomedical Research Centre for Mental Health, Grant/Award Number: NIHR/MRC (14/23/17); NIHR senior investigator award, Grant/Award Number: NF‐SI‐0616‐10040; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433‐09‐ 229; Research Council of Norway, Grant/Award Numbers: #223273, #288083, #230345; South London and Maudsley Trust, Grant/Award Number: 064846; South‐Eastern Norway Regional Health Authority, Grant/Award Numbers: #2017112, #2019069; the Generalitat de Catalunya, Grant/Award Number: 2017SGR01343; the German Research Foundation, Grant/Award Numbers: WA 1539/4‐1, SCHN 1205/3‐1; The Marat{\'o} TV3 Foundation, Grant/Award Numbers: #091710, #091710; UK Medical Research Council Grant, Grant/Award Number: G03001896 to J Kuntsi; Vici Innovation Program, Grant/Award Numbers: 016‐130‐669, 91619115; National Institute of Aging, Grant/Award Number: R03AG064001; National Institute of General Medical Sciences, Grant/Award Number: P20GM130447 Funding information Publisher Copyright: {\textcopyright} 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.",

year = "2022",

month = jan,

doi = "10.1002/hbm.25204",

language = "English",

volume = "43",

pages = "470--499",

journal = "Human Brain Mapping",

issn = "1065-9471",

publisher = "Wiley-Liss Inc.",

number = "1",

}

TY - JOUR

T1 - Greater male than female variability in regional brain structure across the lifespan

AU - Wierenga, Lara M.

AU - Doucet, Gaelle E.

AU - Dima, Danai

AU - Agartz, Ingrid

AU - Aghajani, Moji

AU - Akudjedu, Theophilus N.

AU - Albajes-Eizagirre, Anton

AU - Alnæs, Dag

AU - Alpert, Kathryn I.

AU - Andreassen, Ole A.

AU - Anticevic, Alan

AU - Asherson, Philip

AU - Banaschewski, Tobias

AU - Bargallo, Nuria

AU - Baumeister, Sarah

AU - Baur-Streubel, Ramona

AU - Bertolino, Alessandro

AU - Bonvino, Aurora

AU - Boomsma, Dorret I.

AU - Borgwardt, Stefan

AU - Bourque, Josiane

AU - den Braber, Anouk

AU - Brandeis, Daniel

AU - Breier, Alan

AU - Brodaty, Henry

AU - Brouwer, Rachel M.

AU - Buitelaar, Jan K.

AU - Busatto, Geraldo F.

AU - Calhoun, Vince D.

AU - Canales-Rodríguez, Erick J.

AU - Cannon, Dara M.

AU - Caseras, Xavier

AU - Castellanos, Francisco X.

AU - Chaim-Avancini, Tiffany M.

AU - Ching, Christopher R.K.

AU - Clark, Vincent P.

AU - Conrod, Patricia J.

AU - Conzelmann, Annette

AU - Crivello, Fabrice

AU - Davey, Christopher G.

AU - Dickie, Erin W.

AU - Ehrlich, Stefan

AU - van't Ent, Dennis

AU - Fisher, Simon E.

AU - Fouche, Jean Paul

AU - Franke, Barbara

AU - Fuentes-Claramonte, Paola

AU - de Geus, Eco J.C.

AU - Di Giorgio, Annabella

AU - Glahn, David C.

AU - Gotlib, Ian H.

AU - Grabe, Hans J.

AU - Gruber, Oliver

AU - Gruner, Patricia

AU - Gur, Raquel E.

AU - Gur, Ruben C.

AU - Gurholt, Tiril P.

AU - de Haan, Lieuwe

AU - Haatveit, Beathe

AU - Harrison, Ben J.

AU - Hartman, Catharina A.

AU - Hatton, Sean N.

AU - Heslenfeld, Dirk J.

AU - van den Heuvel, Odile A.

AU - Hickie, Ian B.

AU - Hoekstra, Pieter J.

AU - Hohmann, Sarah

AU - Holmes, Avram J.

AU - Hoogman, Martine

AU - Hosten, Norbert

AU - Howells, Fleur M.

AU - Hulshoff Pol, Hilleke E.

AU - Huyser, Chaim

AU - Jahanshad, Neda

AU - James, Anthony C.

AU - Jiang, Jiyang

AU - Jönsson, Erik G.

AU - Joska, John A.

AU - Kalnin, Andrew J.

AU - Klein, Marieke

AU - Koenders, Laura

AU - Kolskår, Knut K.

AU - Krämer, Bernd

AU - Kuntsi, Jonna

AU - Lagopoulos, Jim

AU - Lazaro, Luisa

AU - Lebedeva, Irina S.

AU - Lee, Phil H.

AU - Lochner, Christine

AU - Machielsen, Marise W.J.

AU - Maingault, Sophie

AU - Martin, Nicholas G.

AU - Martínez-Zalacaín, Ignacio

AU - Mataix-Cols, David

AU - Mazoyer, Bernard

AU - McDonald, Brenna C.

AU - McDonald, Colm

AU - McIntosh, Andrew M.

AU - McMahon, Katie L.

AU - McPhilemy, Genevieve

AU - van der Meer, Dennis

AU - Menchón, José M.

AU - Naaijen, Jilly

AU - Nyberg, Lars

AU - Oosterlaan, Jaap

AU - Paloyelis, Yannis

AU - Pauli, Paul

AU - Pergola, Giulio

AU - Pomarol-Clotet, Edith

AU - Portella, Maria J.

AU - Radua, Joaquim

AU - Reif, Andreas

AU - Richard, Geneviève

AU - Roffman, Joshua L.

AU - Rosa, Pedro G.P.

AU - Sacchet, Matthew D.

AU - Sachdev, Perminder S.

AU - Salvador, Raymond

AU - Sarró, Salvador

AU - Satterthwaite, Theodore D.

AU - Saykin, Andrew J.

AU - Serpa, Mauricio H.

AU - Sim, Kang

AU - Simmons, Andrew

AU - Smoller, Jordan W.

AU - Sommer, Iris E.

AU - Soriano-Mas, Carles

AU - Stein, Dan J.

AU - Strike, Lachlan T.

AU - Szeszko, Philip R.

AU - Temmingh, Henk S.

AU - Thomopoulos, Sophia I.

AU - Tomyshev, Alexander S.

AU - Trollor, Julian N.

AU - Uhlmann, Anne

AU - Veer, Ilya M.

AU - Veltman, Dick J.

AU - Voineskos, Aristotle

AU - Völzke, Henry

AU - Walter, Henrik

AU - Wang, Lei

AU - Wang, Yang

AU - Weber, Bernd

AU - Wen, Wei

AU - West, John D.

AU - Westlye, Lars T.

AU - Whalley, Heather C.

AU - Williams, Steven C.R.

AU - Wittfeld, Katharina

AU - Wolf, Daniel H.

AU - Wright, Margaret J.

AU - Yoncheva, Yuliya N.

AU - Zanetti, Marcus V.

AU - Ziegler, Georg C.

AU - de Zubicaray, Greig I.

AU - Thompson, Paul M.

AU - Crone, Eveline A.

AU - Frangou, Sophia

AU - Tamnes, Christian K.

AU - Karolinska Schizophrenia Project (KaSP) consortium

N1 - Funding Information: The authors declare the following competing interests: OAA: Speaker's honorarium from Lundbeck, Consultant of HealthLyti; PA: Received payments for consultancy to Shire/Takeda, Medic, educational/research awards from Shire/Takeda, GW Pharma, Janssen‐Cila, speaker at sponsored events for Shire, Flynn Pharma, Medic; TB: advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm, conference support or speaker's fee by Lilly, Medice, and Shire, received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press ‐ the present work is unrelated to the above grants and relationship; DB: serves as an unpaid scientific consultant for an EU‐funded neurofeedback trial that is unrelated to the present work; HB: Advisory Board, Nutricia Australi; CRKC: received partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript; BF: received educational speaking fees from Medice; HJG: received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care; NJ and PMT: MPI of a research related grant from Biogen, Inc., for research unrelated to the contents of this manuscript; JK: given talks at educational events sponsored by Medic; all funds are received by King's College London and used for studies of ADHD; DM‐C: receives fees from UpToDate, Inc and Elsevier, all unrelated to the current work; AMM: received research support from Eli Lilly, Janssen, and the Sackler Foundation, and speaker fees from Illumina and Janssen; DJS: received research grants and/or honoraria from Lundbeck and Sun. The remaining authors declare no competing interests. Funding Information: BIG ‐ Nijmegen 1.5T; Deutsche Forschungsgemeinschaft, Grant/Award Numbers: KFO 125, TRR 58/A1, TRR 58/A5, SFB‐TRR 58/B01, SFB‐TRR 58/B06; Deutsche Forschungsgesellschaft collaborative research center, Grant/Award Number: 636; EU H2020, Grant/Award Number: #667302; European Community's Horizon 2020 Programme, Grant/Award Numbers: 643051, 667302; European Community's Seventh Framework Programme, Grant/Award Numbers: 602805, 603016, 602450, 278948; European Research Council, Grant/Award Numbers: ERC‐2010‐StG‐263234, ERC‐230374; German Research Foundation, Grant/Award Number: KFO 125; KA Wallenberg Foundation; KNAW Academy Professor Award, Grant/Award Number: PAH/6635; Miguel Servet Research Contract, Grant/Award Number: CPII16/0020; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: 51.02.061 to H.H., NWO 51.02.062 to D.B., NWO‐ NIH; Netherlands Brain Foundation grant, Grant/Award Number: 2010(1)‐50; NIA, Grant/Award Number: T32AG058507; NIH/NIMH, Grant/Award Numbers: 5T32MH073526, U54EB020403, U54 EB020403, R56 AG058; NIHR Biomedical Research Centre for Mental Health, Grant/Award Number: NIHR/MRC (14/23/17); NIHR senior investigator award, Grant/Award Number: NF‐SI‐0616‐10040; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433‐09‐ 229; Research Council of Norway, Grant/Award Numbers: #223273, #288083, #230345; South London and Maudsley Trust, Grant/Award Number: 064846; South‐Eastern Norway Regional Health Authority, Grant/Award Numbers: #2017112, #2019069; the Generalitat de Catalunya, Grant/Award Number: 2017SGR01343; the German Research Foundation, Grant/Award Numbers: WA 1539/4‐1, SCHN 1205/3‐1; The Marató TV3 Foundation, Grant/Award Numbers: #091710, #091710; UK Medical Research Council Grant, Grant/Award Number: G03001896 to J Kuntsi; Vici Innovation Program, Grant/Award Numbers: 016‐130‐669, 91619115; National Institute of Aging, Grant/Award Number: R03AG064001; National Institute of General Medical Sciences, Grant/Award Number: P20GM130447 Funding information Publisher Copyright: © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

PY - 2022/1

Y1 - 2022/1

N2 - For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

AB - For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

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UR - https://www.mendeley.com/catalogue/24875add-fa6b-3b33-a5c0-c03e2955ab44/

U2 - 10.1002/hbm.25204

DO - 10.1002/hbm.25204

M3 - Article

C2 - 33044802

SN - 1065-9471

VL - 43

SP - 470

EP - 499

JO - Human Brain Mapping

JF - Human Brain Mapping

IS - 1

ER -

Greater male than female variability in regional brain structure across the lifespan

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