Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence

Xinran Wu^#^{1

2}, Kai Zhang^#³, Nanyu Kuang^#⁴, Xiangzhen Kong⁵, Miao Cao^{1

2}, Zhengxu Lian^{1

2}, Yu Liu^{1

2}, Huanxin Fan^{1

2}, Gechang Yu⁶, Zhaowen Liu⁷, Wei Cheng^{1

2}, Tianye Jia^{1

2}, Barbara J Sahakian⁸, Trevor W Robbins^{1

9}, Jianfeng Feng^{1

2

10

11

12

13}, Gunter Schumann^{1

14

15

16}, Lena Palaniyappan^{17

18

19

20}, Jie Zhang^{21

22}

Affiliations

¹ Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, PR China.
² Key Laboratory of Computational Neuroscience and Brain Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, PR China.
³ School of Computer Science and Technology, East China Normal University, Shanghai, China.
⁴ Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
⁵ Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China.
⁶ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong SAR.
⁷ School of Computer Science of Northwestern Polytechnical University, Xi'an, Shanxi, China.
⁸ Department of Psychiatry, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
⁹ Cambridge shire and Peterborough NHS Trust, Elizabeth House, Fulbourn Hospital, Cambridge, UK.
¹⁰ Shanghai Center for Mathematical Sciences, Shanghai, PR China.
¹¹ Department of Computer Science, University of Warwick, Coventry, UK.
¹² Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, PR China.
¹³ Fudan ISTBI-ZJNU Algorithm Centre for Brain-inspired Intelligence, Zhejiang Normal University, Jinhua, PR China.
¹⁴ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, Hong Kong SAR.
¹⁵ PONS Centre, Charite Mental Health, Dept. of Psychiatry and Psychotherapie, CCM, Charite Universitaetsmedizin Berlin, Berlin, Germany.
¹⁶ The Centre for Population Neuroscience and Stratified Medicine (PONS), ISTBI, Fudan University, Shanghai, China.
¹⁷ Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada. lena.palaniyappan@mcgill.ca.
¹⁸ Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. lena.palaniyappan@mcgill.ca.
¹⁹ Robarts Research Institute, University of Western Ontario, London, ON, Canada. lena.palaniyappan@mcgill.ca.
²⁰ Department of Medical Biophysica, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. lena.palaniyappan@mcgill.ca.
²¹ Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, PR China. zhangjie80@fudan.edu.cn.
²² Key Laboratory of Computational Neuroscience and Brain Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, PR China. zhangjie80@fudan.edu.cn.

^# Contributed equally.

PMID: 40368909
DOI: 10.1038/s41467-025-59110-9

Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence

Xinran Wu et al. Nat Commun. 2025.

. 2025 May 14;16(1):4480.

doi: 10.1038/s41467-025-59110-9.

Authors

Affiliations

¹ Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, PR China.
² Key Laboratory of Computational Neuroscience and Brain Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, PR China.
³ School of Computer Science and Technology, East China Normal University, Shanghai, China.
⁴ Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
⁵ Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China.
⁶ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong SAR.
⁷ School of Computer Science of Northwestern Polytechnical University, Xi'an, Shanxi, China.
⁸ Department of Psychiatry, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
⁹ Cambridge shire and Peterborough NHS Trust, Elizabeth House, Fulbourn Hospital, Cambridge, UK.
¹⁰ Shanghai Center for Mathematical Sciences, Shanghai, PR China.
¹¹ Department of Computer Science, University of Warwick, Coventry, UK.
¹² Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, PR China.
¹³ Fudan ISTBI-ZJNU Algorithm Centre for Brain-inspired Intelligence, Zhejiang Normal University, Jinhua, PR China.
¹⁴ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, Hong Kong SAR.
¹⁵ PONS Centre, Charite Mental Health, Dept. of Psychiatry and Psychotherapie, CCM, Charite Universitaetsmedizin Berlin, Berlin, Germany.
¹⁶ The Centre for Population Neuroscience and Stratified Medicine (PONS), ISTBI, Fudan University, Shanghai, China.
¹⁷ Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada. lena.palaniyappan@mcgill.ca.
¹⁸ Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. lena.palaniyappan@mcgill.ca.
¹⁹ Robarts Research Institute, University of Western Ontario, London, ON, Canada. lena.palaniyappan@mcgill.ca.
²⁰ Department of Medical Biophysica, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. lena.palaniyappan@mcgill.ca.
²¹ Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, PR China. zhangjie80@fudan.edu.cn.
²² Key Laboratory of Computational Neuroscience and Brain Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, PR China. zhangjie80@fudan.edu.cn.

^# Contributed equally.

PMID: 40368909
DOI: 10.1038/s41467-025-59110-9

Erratum in

Author Correction: Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence.
Wu X, Zhang K, Kuang N, Kong X, Cao M, Lian Z, Liu Y, Fan H, Yu G, Liu Z, Cheng W, Jia T, Sahakian BJ, Robbins TW, Feng J, Schumann G, Palaniyappan L, Zhang J. Wu X, et al. Nat Commun. 2025 Jul 9;16(1):6325. doi: 10.1038/s41467-025-61785-z. Nat Commun. 2025. PMID: 40634360 Free PMC article. No abstract available.

Abstract

Cerebral asymmetry, fundamental to various cognitive functions, is often disrupted in neuropsychiatric disorders. While brain growth has been extensively studied, the maturation of brain asymmetry in children and the factors influencing it in adolescence remain poorly understood. We analyze longitudinal data from 11,270 children aged 10-14 years in the Adolescent Brain Cognitive Development (ABCD) study. Our analysis maps the developmental trajectory of structural brain asymmetry. We identify significant age-related, modality-specific development patterns. These patterns link to crystallized intelligence and mental health problems, but with weak correlations. Genetically, structural asymmetry relates to synaptic processes and neuron projections, likely through asymmetric synaptic pruning. At the microstructural level, corpus callosum integrity emerged as a key factor modulating the developing asymmetry. Environmentally, favorable perinatal conditions were associated with prolonged corpus callosum development, which affected future asymmetry patterns and cognitive outcomes. These findings underscore the dynamic yet predictable interactions between brain asymmetry, its structural determinants, and cognitive and psychiatric outcomes during a pivotal developmental stage. Our results provide empirical support for the adaptive plasticity theory in cerebral asymmetry and offer insights into both cognitive maturation and potential risk for early-onset mental health problems.

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Conflict of interest statement

Competing interests: L.P. reports personal fees for serving as chief editor from the Canadian Medical Association Journals, speaker/consultant fee from Janssen Canada and Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work.

References

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61973086/National Natural Science Foundation of China (National Science Foundation of China)

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Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence

Affiliations

Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

MeSH terms

Grants and funding

LinkOut - more resources

Medical