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Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants
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Abstract
Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44-77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. 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 study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.
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“Sex-related differences in brain structure and function have been consistently reported across large-scale neuroimaging studies, involving both global and regional measures such as total brain volume, cortical thickness, white matter microstructure, and functional connectivity [29,30,31,32].”
From Benchmarking Multimodal Deep Fusion Strategies for Heterogeneous Neuroimaging and Cognitive Data Using a Controlled Sex Classification Task (2026) · cites this paper as [31]
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“As sex differences exist in brain morphology,33”
From Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults (2019) · cites this paper as [33]
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“Memory impairment is similarly found among patients with Cushing disease and Cushing syndrome (694).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [694]
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Self-citationSex differences in the brain: More than just male or female
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“This is in line with previous studies that found differences in static (Ritchie et al., 2018) and dynamic (Scofield et al., 2019) 4 (occipito-parietal, somatomotor).”
ResultStimulus Selection Influences Prediction of Individual Phenotypes in Naturalistic Conditions
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APOE4-related differences in cortical thickness are modulated by sex in middle age
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“Females had thicker cortices within frontal, temporal, and parietal regions compared to males (Im et al., 2006; Ritchie et al., 2018; Sowell et al., 2007).”
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“Males have on average a larger brain than females [141–143].”
Matijevic, S., & Ryan, L. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1562660 · Cited by 7
“…has been largely focused on FA and rather mixed, with some studies reporting higher FA values in white matter among females relative to males (Kanaan et al., 2014; Kochunov et al., 2015; Herlin et al., 2024) and others reporting the opposite (Matijevic and Ryan, 2021; Ritchie et al., 2018).”
Gender Differences in the Effects of Exercise Interventions on Alzheimer’s Disease
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“Ritchie et al. found that female brains tend to atrophy more rapidly during cognitive and neurodegenerative decline [71].”
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“Since levels of FA are often higher in men compared to women [54, 55], we analyzed our DTI data regarding potential sex differences.”
Khodanovich, M. Y., Светлик, М. В., Naumova, A. V., Usova, A. V., Pashkevich, V., Moshkina, M., Shadrina, M. M., Kamaeva, D. A., Obukhovskaya, V. B., Kataeva, N. G., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13237065 · Cited by 6
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“While atrophy rates in the brain are similar [115], men tend to start with larger volumes, mainly due to larger head-sizes [116].”
Using an ordinary differential equation model to separate rest and task signals in fMRI
Kashyap, A., Geenjaar, E., Bey, P., Dhindsa, K., Glomb, K., Plis, S., Keilholz, S. D., & Ritter, P. (2025) · Nature Communications · doi:10.1038/s41467-025-62491-6 · Cited by 6
“Moreover, the analysis assumes that the development of the cortex is almost stationary and does not take into account any effects of aging, as well as known gender differences that affect cortical organizations and dynamics 56,57 .”
Koss, M. P., Hansen, M., Anderson, E. J., Bach, M. H., & Bramsen, R. H. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108561716.035 · Cited by 5
Unveiling Fairness Biases in Deep Learning-Based Brain MRI Reconstruction
Du, Y., Xue, Y., Dharmakumar, R., & Tsaftaris, S. A. (2023) · Lecture notes in computer science · doi:10.1007/978-3-031-45249-9_10 · Cited by 5
Fu, G.-J., Wang, L., Chi, X., Liang, X., Wei, J., Huang, Z., Shen, W. G., & Zhang, Y. (2024) · Current Pain and Headache Reports · doi:10.1007/s11916-024-01238-2 · Cited by 5
“(a) There is a sex difference in pain perception, which may be related to the regulation of pain by hormones as well as differences in brain structural development and functionality (such as the volume of different cortical areas associated with pain) [28, 29].”
BackgroundSpets, D. S., Cohen, J. E., Konishi, K., Aroner, S. A., Misra, M., Lee, H., & Goldstein, J. M. (2024) · Cerebral Cortex · doi:10.1093/cercor/bhae088 · Cited by 6
Examining the neurostructural architecture of intelligence: The Lothian Birth Cohort 1936 study
Page, D., Buchanan, C. R., Moodie, J. E., Harris, M. A., Taylor, A. M., Hernández, M. V., Maniega, S. M., Corley, J., Bastin, M. E., Wardlaw, J. M., et al. (2024) · Cortex · doi:10.1016/j.cortex.2024.06.007 · Cited by 4
“Thereisamodestbutreplicablepositivecorrelationbetween total brain volume and g , with estimates of magnitude tending to fall around r ¼ ~.28 (Cox et al., 2019; Gignac & Bates, 2017; McDaniel, 2005; Pietschnig et al., 2015; Ritchie et al., 2018).”
BackgroundSelf-citationHe, S., Zhang, X., & Zhu, H. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00659-3 · Cited by 5
“Data from the UK Biobank database indicate that brain volume and cortical thickness show sex bias [62]; genes show sex-biased expression in the cerebral cortex and in specific developmental periods [5–7]; gene expression shows more cross-species divergence in microglia, astrocytes, and…”
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Longitudinal changes in brain asymmetry track lifestyle and disease
Saltoun, K., Yeo, B. T. T., Paul, L. K., Diedrichsen, J., & Bzdok, D. (2025) · Nature Communications · doi:10.1038/s41467-025-60451-8 · Cited by 6
Graph Spectral Characterization of Brain Cortical Morphology
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“Variations in the cortical morphology of male and female subjects have been suggested in many studies, see for ex-l ample [17].”
Endocranial volume is variable and heritable, but not related to fitness, in a free-ranging primate
Colby, A. E., Kimock, C. M., & Higham, J. P. (2021) · Scientific Reports · doi:10.1038/s41598-021-81265-w · Cited by 5
Parsimonious model for mass-univariate vertexwise analysis
Couvy‐Duchesne, B., Zhang, F., Kemper, K. E., Sidorenko, J., Wray, N. R., Visscher, P. M., Colliot, O., & Yang, J. (2022) · Journal of medical imaging · doi:10.1117/1.jmi.9.5.052404 · Cited by 5
Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease
Wang, C., Wang, J., Wu, X., Liu, T., Feng, W., Zhou, H., Chen, C., Shi, L., Lin, M., Liu, T., et al. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14447 · Cited by 5
“19 For the purpose of reducing the influence of social factors on SD, 27 explained that marmoset females perform worse than males in reverse learning tasks.”
BackgroundSex/Gender Differences in the Human Brain
Hodgetts, S., & Hausmann, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.24103-5 · Cited by 5
Zhou, X., Wu, R., Zeng, Y., Qi, Z., Ferraro, S., Yao, S., Kendrick, K. M., & Becker, B. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.09.434531 · Cited by 5
Analyzing brain data by sex: Are we asking the right question?Preprint
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“, 2018), sex (Amunts et al., 2007; Barnes et al., 2010; Barta and Dazzan, 2003; Luders et al., 2006; Ritchie et al., 2018) and eTIV (Barnes et al.”
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Effects of high-concentration aromatic environments on sleep quality: Taking bergamot as an example
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“…metrics in the brain white matter by Kochunov et al. (2012), Lawrence et al. (2021), Lebel et al. (2012), Mendez Colmenares et al. (2023), Ritchie et al. (2018), Szeszko et al. (2003), Toschi et al. (2020) and of macrostructural metrics in gray matter by Raz (1997); Wang et al. (2019);…”
Mucida‐Alvim, D., Hernández, M. D. C. V., Bastin, M. E., Clancy, Ú., Arteaga, C., Wiseman, S. J., Jochems, A. C. C., García, D. J., Hamilton, O. K., Backhouse, E., et al. (2026) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2026.03.005 · Cited by 4
Self-citationAndrogen activity in the male embryonic hindbrain drives lethal PFA ependymoma
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“Male individuals have larger brains overall—and larger cerebella, specifi-cally—than female individuals do, even after accounting for weight and height 38–40 .”
Coverdale, N. S., Champagne, A. A., Allen, M. D., Tremblay, J. C., Ethier, T. S., Fernández-Ruíz, J., Marshall, R. A., MacPherson, R. E. K., Pyke, K. E., Cook, D. J., et al. (2024) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00270.2023 · Cited by 4
How the Effect of Virtual Reality on Cognitive Functioning Is Modulated by Gender Differences
Righi, S., Gavazzi, G., Benedetti, V., Raineri, G., & Viggiano, M. P. (2024) · Bioengineering · doi:10.3390/bioengineering11040408 · Cited by 4
Chen, W.-Y., Ling, Z., & Jia, T. (2024) · Entropy · doi:10.3390/e26100864 · Cited by 4
“Several studies report stronger intra-module connections in females and stronger inter-module connections in males [17,19], implying that males and females may have different hierarchical organization in their brain networks.”
BackgroundResultSilva, R. F., Damaraju, E., Li, X., Kochunov, P. V., Belger, A., Ford, J. M., Mathalon, D. H., Mueller, B. A., Potkin, S. G., Preda, A., et al. (2024) · Human Brain Mapping · doi:10.1002/hbm.70037 · Cited by 4
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“Brain size effects could be adjusted by the general linear model for some variables, but other complex variables in tractography may have nonlinear trends (Ritchie et al. 2018).”
Sex Differences in Neurodevelopment and Its Disorders
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“Furthermore, functional brain networks differed between males and females, with stronger connectivity for males in unimodal sensorimotor cortices and stronger connectivity for females in the default mode network (87).”
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“Somepreviousstudies usedtotalgraymattervolumetonormalizetheatro-phy[20,51],butitwasalsofoundthatseveral regionalsexdifferencesremainevenafteradjust-ing for overall brain size [50, 52].”
McLamb, F., Feng, Z., Vu, J. P., Griffin, L., Vasquez, M. F., & Bozinovic, G. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04427-7 · Cited by 3
Metadata
- Authors
- Ritchie, S. J., Cox, S. R., Shen, X., Lombardo, M. V., Reus, L. M., Alloza, C., Harris, M. A., Alderson, H. L., Hunter, S., Neilson, E., Liewald, D. C. M., Auyeung, B., Whalley, H. C., Lawrie, S. M., Gale, C. R., Bastin, M. E., McIntosh, A. M., & Deary, I. J.
- Affiliations
- University of Edinburgh (GB)
- University of Cambridge (GB)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Queen Margaret Hospital (GB)
- NHS Lothian (GB)
- Department of Psychology, The University of Edinburgh, Edinburgh, UK
- Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
- Corresponding author
- Ritchie, Stuart J
- ORCID
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-05-16
- Volume
- 28
- Issue
- 8
- Pages
- 2959-2975
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC6041980
- OpenAlex
- W2952574438
- Cited by
- 855
- References
- 125
- Citations by year
- 2026: 75 · 2025: 86 · 2024: 101 · 2023: 110 · 2022: 105 · 2021: 130 · 2020: 138 · 2019: 68 · 2018: 35
- FWCI
- 88.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cerebral Cortex (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- OSF Preprints (OSF Preprints) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- CCACE (MR/K026992/1)
- MRC (MR/M013111/1)
- Dementias Platform UK (MR/L015382/1)
- STRADL (104036/Z/14/Z)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- sex differences, adult human brain, brain structure, brain function, brain volume, cortical thickness, white matter fractional anisotropy, functional connectome, default mode network, sensorimotor cortex, UK Biobank
- MeSH terms
- Adult, Aged, Brain, Brain Mapping, Female, United Kingdom, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen, Rest, Sex Characteristics, Biological Specimen Banks, Community Health Planning, Connectome, White Matter
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