Developing brain asymmetry shapes cognitive and psychiatric outcomes in adolescence

Xinran Wu, Kai Zhang, Nanyu Kuang, Xiangzhen Kong, Miao Cao, Zhengxu Lian, Yu Liu, Huanxin Fan, Gechang Yu, Zhaowen Liu, Wei Cheng, Tianye Jia, Barbara J. Sahakian, Trevor W. Robbins, Jianfeng Feng, Gunter Schumann, Lena Palaniyappan () and Jie Zhang ()
Additional contact information
Xinran Wu: Fudan University
Kai Zhang: East China Normal University
Nanyu Kuang: National Institutes of Health
Xiangzhen Kong: Zhejiang University
Miao Cao: Fudan University
Zhengxu Lian: Fudan University
Yu Liu: Fudan University
Huanxin Fan: Fudan University
Gechang Yu: The Chinese University of Hong Kong, Prince of Wales Hospital
Zhaowen Liu: School of Computer Science of Northwestern Polytechnical University
Wei Cheng: Fudan University
Tianye Jia: Fudan University
Barbara J. Sahakian: University of Cambridge
Trevor W. Robbins: Fudan University
Jianfeng Feng: Fudan University
Gunter Schumann: Fudan University
Lena Palaniyappan: McGill University
Jie Zhang: Fudan University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59110-9

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