Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Summary 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.
Authors: Minhui Zhu, Lianglong Sun, Mingrui Xia, Yanchao Bi, Qingjiu Cao, Rui Chen, Yuan Chen, Taolin Chen, Yuqi Cheng, Zhengjia Dai, Yao Deng, Yuyin Ding, Qi Dong, Jia-Hong Gao, Qiyong Gong, Ying Han, Zaizhu Han, Chu-Chung Huang, Hao Huang, Ruiwang Huang, Ran Huo, Lingjiang Li, Qixiang Lin, Bangshan Liu, Chao Liu, Hesheng Liu, Ningyu Liu, Ying Liu, Yong Liu, Jing Lu, Leilei Ma, Weiwei Men, Chenxuan Pang, Shaozheng Qin, Wen Qin, Jiang Qiu, Shijun Qiu, Tianmei Si, Shuping Tan, Yanqing Tang, Sha Tao, Dawei Wang, Fei Wang, Jiali Wang, Pan Wang, Qian Wang, Xiaoqin Wang, Yanpei Wang, Dongtao Wei, Yankun Wu, Peng Xie, Xiufeng Xu, Li Yang, Chunshui Yu, Huishu Yuan, Haibo Zhang, Xi Zhang, Gai Zhao, Kun Zhao, Yanting Zheng, Alzheimer’s Disease Neuroimaging Initiative, MCADI, DIDA-MDD Working Group, Xinyuan Liang, Yong He
Institutions: Beijing Normal University, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Zhuhai, Peking University, Peking University Sixth Hospital, First Affiliated Hospital of Zhengzhou University, Sichuan University, West China Medical Center of Sichuan University, West China Hospital of Sichuan University, First Affiliated Hospital of Kunming Medical University, Xuan Wu Hospital of the Capital Medical University, East China Normal University, Children's Hospital of Philadelphia, University of Pennsylvania, South China Normal University, Peking University Third Hospital, Central South University, Second Xiangya Hospital of Central South University, Hunan Institute of Mental Health, Changping Laboratory, Beijing University of Posts and Telecommunications, Chinese Institute for Brain Research, Tianjin Medical University General Hospital, State Key Laboratory of Experimental Hematology, Tianjin Medical University, Southwest University, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Beijing HuiLongGuan Hospital, Sheng Jing Hospital, Qilu Hospital of Shandong University, First Hospital of China Medical University, Tianjin University, Tianjin Huanhu Hospital, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chinese PLA General Hospital
Language: English
Topic: Sex and Gender in Healthcare
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221762114