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Sex differences in the adult human brain: Evidence from 5,216 UK Biobank participants

Stuart J. Ritchie, Simon R. Cox, Xueyi Shen, Michael V. Lombardo, Lianne M. Reus, Clara Alloza, Matthew A. Harris, Helen L. Alderson, Stuart Hunter, Emma Neilson, David C. M. Liewald, Bonnie Auyeung, Heather C. Whalley, Stephen M. Lawrie, Catharine R. Gale, Mark E. Bastin, Andrew M. McIntosh, Ian J. Deary
doi: https://doi.org/10.1101/123729
Stuart J. Ritchie
1Department of Psychology, The University of Edinburgh, Edinburgh, UK
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
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  • For correspondence: stuart.ritchie@ed.ac.uk
Simon R. Cox
1Department of Psychology, The University of Edinburgh, Edinburgh, UK
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
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Xueyi Shen
3Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
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Michael V. Lombardo
4Department of Psychology and Center for Applied Neuroscience, University of Cyprus, Nicosia, Cyprus
5Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK
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Lianne M. Reus
6Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
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Clara Alloza
3Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
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Matthew A. Harris
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
3Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
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Helen L. Alderson
7Department of Psychiatry, Queen Margaret Hospital, Dunfermline, UK
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Stuart Hunter
8NHS Lothian, Edinburgh, UK
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Emma Neilson
3Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
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David C. M. Liewald
1Department of Psychology, The University of Edinburgh, Edinburgh, UK
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
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Bonnie Auyeung
1Department of Psychology, The University of Edinburgh, Edinburgh, UK
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Heather C. Whalley
3Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
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Stephen M. Lawrie
3Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
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Catharine R. Gale
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
9MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
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Mark E. Bastin
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
10Brain Research Imaging Centre, The University of Edinburgh, Edinburgh, UK
11Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
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Andrew M. McIntosh
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
3Division of Psychiatry, The University of Edinburgh, Edinburgh, UK
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Ian J. Deary
1Department of Psychology, The University of Edinburgh, Edinburgh, UK
2Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
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Summary

Sex differences in human brain structure and function are of substantial scientific interest because of sex-differential susceptibility to psychiatric disorders [1,2,3] and because of the potential to explain sex differences in psychological traits [4]. Males are known to have larger brain volumes, though the patterns of differences across brain subregions have typically only been examined in small, inconsistent studies [5]. In addition, despite common findings of greater male variability in traits like intelligence [6], personality [7], and physical performance [8], variance differences in the brain have received little attention. Here we report the largest single-sample study of structural and functional sex differences in the human brain to date (2,750 female and 2,466 male participants aged 44-77 years). Males had higher cortical and sub-cortical volumes, cortical surface areas, and white matter diffusion directionality; females had thicker cortices and higher white matter tract complexity. Considerable overlap between the distributions for males and females was common, and subregional differences were smaller after accounting for global differences. There was generally greater male variance across structural measures. The modestly higher male score on two cognitive tests was partly mediated via structural differences. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale characterisation of neurobiological sex differences provides a foundation for attempts to understand the causes of sex differences in brain structure and function, and their associated psychological and psychiatric consequences.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 14, 2017.
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Sex differences in the adult human brain: Evidence from 5,216 UK Biobank participants
Stuart J. Ritchie, Simon R. Cox, Xueyi Shen, Michael V. Lombardo, Lianne M. Reus, Clara Alloza, Matthew A. Harris, Helen L. Alderson, Stuart Hunter, Emma Neilson, David C. M. Liewald, Bonnie Auyeung, Heather C. Whalley, Stephen M. Lawrie, Catharine R. Gale, Mark E. Bastin, Andrew M. McIntosh, Ian J. Deary
bioRxiv 123729; doi: https://doi.org/10.1101/123729
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Sex differences in the adult human brain: Evidence from 5,216 UK Biobank participants
Stuart J. Ritchie, Simon R. Cox, Xueyi Shen, Michael V. Lombardo, Lianne M. Reus, Clara Alloza, Matthew A. Harris, Helen L. Alderson, Stuart Hunter, Emma Neilson, David C. M. Liewald, Bonnie Auyeung, Heather C. Whalley, Stephen M. Lawrie, Catharine R. Gale, Mark E. Bastin, Andrew M. McIntosh, Ian J. Deary
bioRxiv 123729; doi: https://doi.org/10.1101/123729

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