Cited by 855Sex and Gender in HealthcareAdvanced Neuroimaging Techniques and ApplicationsFunctional Brain Connectivity Studies

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Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants

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Ritchie, Stuart J, Cox, Simon R, Shen, Xueyi, Lombardo, Michael V, Reus, Lianne M, Alloza, Clara, Harris, Mathew A, Alderson, Helen L, Hunter, Stuart, Neilson, Emma, Liewald, David C M, Auyeung, Bonnie, Whalley, Heather C, Lawrie, Stephen M, Gale, Catharine R, Bastin, Mark E, McIntosh, Andrew M, Deary, Ian J·2018·Cerebral Cortex

DOI 10.1093/cercor/bhy109PMC PMC6041980

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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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BackgroundResult
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Self-citation
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Background
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Spatial navigation skills in older adults with and without cognitive impairment
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Enduring prenatal androgen effects on the female brain
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“3,8 However, definite conclusions are difficult because existing CAH research was based on small sample sizes 3 and potentially under-powered studies (i.e. any significant effects might be small in size as also shown for a number of sex differences independent of CAH 9,10 ).”
Exploring mesoscale brain connectivity variations and developing sex-specific tractography templates
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“…the adjustment measure for the vertexwise cortical volume analyses, total surface area (TSA) for the vertexwise SA, and mean cortical thickness (MCT) for the vertexwise CT, as employed in some studies using surface-based measurements ( Ritchie et al., 2018; Westman et al., 2013; Zhou et al., 2014).”
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“38 For example, the frontal lobe receives significant perfusion in both sexes, but is even greater in females.”
Influential
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“It may also be that sex differences in the neuroimaging and behavioral features examined herein show stronger inter-relationships during dynamic windows of sex-biased brain development 17,79,80 and ageing 81 .”
Substantial evidence against sex differences in bed nucleus of the stria terminalis volume in the human brain
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“…neuroimaging research projects investigating general sex differences in brain region size have portrayed a complex set of results ( DeCasien et al., 2022; Eliot et al., 2021; Lotze et al., 2019; Ritchie et al., 2018; Ruigrok et al., 2014; Sanchis-Segura et al., 2019; C. M. Williams et al., 2021a).”
Indian Women Leaders in the NGO Sector
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“In concordance with both the above within-male and within-female ROI comparisons and with the existing literature examining general sex differences in the adult human brain, the direct comparison of Disc1 svD2 male to Disc1 svD2 female rats demonstrates that FA values are significantly lower in female rats than in mal…”
Result
The contributions of brain structural and functional variance in predicting age, sex and treatment
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“N.-X. Chen et al. compensatory mechanisms to reduce functional discrepancies between males and females (De Vries, 2004; McCarthy and Arnold, 2011; Ritchie et al., 2018).”
Sex Differences in the Human Brain
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Personalized estimates of morphometric similarity in multiple sclerosis and neuromyelitis optica spectrum disorders
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“The influence of advancing age and sex on the PBSI measures always be included (Doucet et al., 2019), since age and sex are major contributors to brain structural variation (Dima et al., 2022; Frangou et al., 2022; Ritchie et al., 2018; Wierenga et al., 2018).”
Background
Brain structure alterations following neonatal exposure to low‐frequency electromagnetic fields: A histological analysis
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“Brain regions exhibiting sexual dimorphism encompass the amygdala, hippocampus and vasculature, influencing patterns of cerebral blood flow (Kaczkurkin et al., 2019; Ritchie et al., 2017).”
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“As prior research has established structural and functional brain differences (Ritchie et al., 2018) and brain activity differences between males and females, this may have affected the GCSR observed.”
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“Studies have identified sex differences in brain structure and function using multimodal MRI with key biomarkers, such as ReHo, gray matter volume (GMV), and fractional anisotropy (FA) (Ritchie et al., 2018; Zhang et al., 2020a).”
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“Longitudinal studies, functional MRI, or non-invasive brain stimulation may provide further insight into these relationships.”
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“In contrast, Ritchie [4] discovered signi ﬁ cant differences in brain structure, connectivity, and function between males and females.”
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“When applying the conversion of the endocranium to brain volume, reducing the value by 9.81% (Mo-raes et al. 2023), the volume is 1305 cm³, which falls within the standard devia - tion for modern men, which is 1234 cm³ (± 98) (Ritchie et al. 2018).”
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Structural brain differences do not mediate the relations between sex and personality or psychopathology
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Background
INSIDER: Interpretable sparse matrix decomposition for RNA expression data analysis
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“Therefore, when using data from Ritchie et al. (2018), Zlatý kůň 1’s brain is 3.53 SD above the average for females.”
MethodResultInfluential
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“The present analyses confirmed previous reports of sex differences in FA in the brains of females and males population (Ritchie et al., 2018; Tamnes et al., 2018; van Hemmen et al., 2017) and revealed significant sex differences in predictive associations between CADS dispositional constructs rated…”
BackgroundMethodResult
Girls, Boys, and Schools
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“…GLM approaches could contain many redundant associations, some of which are likely to be false positives induced by confounding factors that cause correlation between vertices (e.g. (Cox et al., 2019; Navas-Sanchez et al., 2016; Ritchie et al., 2018; Tamnes et al., 2017), see also Figure 1b).”
Background
An atlas of trait associations with resting-state and task-evoked human brain functional architectures in the UK BiobankPreprint
Zhao, B., Li, T., Li, Y., Fan, Z., Xiong, D., Wang, X., Gao, M., Smith, S. M., & Hongtu Zhu, B. (2022) · medRxiv · doi:10.1101/2022.02.22.22271371 · Cited by 2
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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: Ritchie, Stuart J
Shen, Xueyi
Lombardo, Michael V
Reus, Lianne M
Alloza, Clara
Harris, Mathew A
Neilson, Emma
Liewald, David C M
Whalley, Heather C
Lawrie, Stephen M
Bastin, Mark E
McIntosh, Andrew M
Deary, Ian J
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
DOI: 10.1093/cercor/bhy109
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: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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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Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants

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