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

Karolinska Schizophrenia Project Consortium (KaSP)

doi:10.1002/hbm.25204

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

Karolinska Schizophrenia Project Consortium (KaSP)

Department of Psychology, Education and Child Studies

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

60 Citations (Scopus)

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
Journal	Human Brain Mapping
DOIs	https://doi.org/10.1002/hbm.25204
Publication status	Accepted/In press - 12 Oct 2020

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

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

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@article{1ed509c5eb3949b09ee2e6c06f0599b4,

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 = "{Karolinska Schizophrenia Project Consortium (KaSP)} and 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 Giorgio, {Annabella Di} and Crone, {Eveline A.}",

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 = "2020",

month = oct,

day = "12",

doi = "10.1002/hbm.25204",

language = "English",

journal = "Human Brain Mapping",

issn = "1065-9471",

publisher = "Wiley-Liss Inc.",

}

TY - JOUR

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

AU - Karolinska Schizophrenia Project Consortium (KaSP)

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 - Giorgio, Annabella Di

AU - Crone, Eveline A.

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 - 2020/10/12

Y1 - 2020/10/12

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.

UR - http://www.scopus.com/inward/record.url?scp=85092397145&partnerID=8YFLogxK

U2 - 10.1002/hbm.25204

DO - 10.1002/hbm.25204

M3 - Article

AN - SCOPUS:85092397145

SN - 1065-9471

JO - Human Brain Mapping

JF - Human Brain Mapping

ER -

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

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