Charting sex divergence in the human brain across the lifespan
Abstract
Biological sex fundamentally shapes human brain organization, but sex-specific normative neuroanatomical trajectories across the lifespan remain largely uncharted. Here, we constructed independent, sex-specific lifespan brain charts using structural neuroimaging data from 59,915 healthy individuals (29,760 males and 30,155 females) ranging in age from 266 postconception days to 100 years. By examining 296 structural phenotypes across global, cortical, and subcortical measures, these models revealed widespread sex differences in maturational timing, with males reaching peak milestones later than females. These trajectories demonstrate that sex differences evolve dynamically, with phenotype-specific windows of emergence and maximal separation. Compared with conventional sex-pooled references, sex-specific models achieved superior predictive accuracy and reduced misestimation of individual deviations in healthy populations. Across five neuropsychiatric conditions, sex-specific models improved the detection of extreme deviations and revealed both shared and sex-dependent patterns of disorder-related neuroanatomical abnormalities. These sex-specific charts establish tailored normative references for assessing brain development, ageing, and disease.
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BibTeX
@misc{zhu2026charting,
title = {{Charting sex divergence in the human brain across the lifespan}},
author = {M. Zhu and L. Sun and M. Xia and Y. Bi and Q. Cao and R. Chen and Y. Chen and T. Chen and Y. Cheng and Z. Dai and Y. Deng and Y. Ding and Q. Dong and J.-H. Gao and Q. Gong and Y. Han and Z. Han and C.-C. Huang and H. Huang and R. Huang and R. Huo and L. Li and Q. Lin and B. Liu and C. Liu and H. Liu and N. Liu and Y. Liu and Y. Liu and J. Lu and L. Ma and W. Men and C. Pang and S. Qin and W. Qin and J. Qiu and S. Qiu and T. Si and S. Tan and Y. Tang and S. Tao and D. Wang and F. Wang and J. Wang and P. Wang and Q. Wang and X. Wang and Y. Wang and D. Wei and Y. Wu and P. Xie and X. Xu and L. Yang and C. Yu and H. Yuan and H. Zhang and X. Zhang and G. Zhao and K. Zhao and Y. Zheng},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.11.758308},
url = {https://www.biorxiv.org/content/10.64898/2026.10.11.758308v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Charting sex divergence in the human brain across the lifespan
AU - M. Zhu
AU - L. Sun
AU - M. Xia
AU - Y. Bi
AU - Q. Cao
AU - R. Chen
AU - Y. Chen
AU - T. Chen
AU - Y. Cheng
AU - Z. Dai
AU - Y. Deng
AU - Y. Ding
AU - Q. Dong
AU - J.-H. Gao
AU - Q. Gong
AU - Y. Han
AU - Z. Han
AU - C.-C. Huang
AU - H. Huang
AU - R. Huang
AU - R. Huo
AU - L. Li
AU - Q. Lin
AU - B. Liu
AU - C. Liu
AU - H. Liu
AU - N. Liu
AU - Y. Liu
AU - Y. Liu
AU - J. Lu
AU - L. Ma
AU - W. Men
AU - C. Pang
AU - S. Qin
AU - W. Qin
AU - J. Qiu
AU - S. Qiu
AU - T. Si
AU - S. Tan
AU - Y. Tang
AU - S. Tao
AU - D. Wang
AU - F. Wang
AU - J. Wang
AU - P. Wang
AU - Q. Wang
AU - X. Wang
AU - Y. Wang
AU - D. Wei
AU - Y. Wu
AU - P. Xie
AU - X. Xu
AU - L. Yang
AU - C. Yu
AU - H. Yuan
AU - H. Zhang
AU - X. Zhang
AU - G. Zhao
AU - K. Zhao
AU - Y. Zheng
PY - 2026
DA - 2026/10/11
PB - bioRxiv
DO - 10.64898/2026.10.11.758308
UR - https://www.biorxiv.org/content/10.64898/2026.10.11.758308v1
AB - Biological sex fundamentally shapes human brain organization, but sex-specific normative neuroanatomical trajectories across the lifespan remain largely uncharted. Here, we constructed independent, sex-specific lifespan brain charts using structural neuroimaging data from 59,915 healthy individuals (29,760 males and 30,155 females) ranging in age from 266 postconception days to 100 years. By examining 296 structural phenotypes across global, cortical, and subcortical measures, these models revealed widespread sex differences in maturational timing, with males reaching peak milestones later than females. These trajectories demonstrate that sex differences evolve dynamically, with phenotype-specific windows of emergence and maximal separation. Compared with conventional sex-pooled references, sex-specific models achieved superior predictive accuracy and reduced misestimation of individual deviations in healthy populations. Across five neuropsychiatric conditions, sex-specific models improved the detection of extreme deviations and revealed both shared and sex-dependent patterns of disorder-related neuroanatomical abnormalities. These sex-specific charts establish tailored normative references for assessing brain development, ageing, and disease.
ER -