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.
“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]
Sex differences exist in brain morphology.
“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]
Memory impairment is similarly found among patients with Cushing disease and Cushing syndrome.
“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]
The Results section on neurostructural and cognitive differences reports correlations with cognitive-test performance, not memory impairment in patients. Searches for Cushing disease, Cushing syndrome, and hypercortisolism found no passage addressing the claimed patient groups. (LLM, conf=0.76)
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- 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 · 2017: 6
- 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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