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Rightward brain structural asymmetry in young children with autism

Molecular Psychiatry volume 30, pages 2860–2870 (2025)Cite this article

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Abstract

To understand the neural mechanism of autism spectrum disorder (ASD) and developmental delay/intellectual disability (DD/ID) that can be associated with ASD, it is important to investigate individuals at an early stage with brain, behavioural and also genetic measures, but such research is still lacking. Here, using the cross-sectional sMRI data of 1030 children under 8 years old, we employed developmental normative models to investigate the atypical development of gray matter volume (GMV) asymmetry in individuals with ASD without DD/ID, ASD with DD/ID and individuals with only DD/ID, and their associations with behavioral and clinical measures and transcription profiles. By extracting the individual deviations of patients from the typical controls with normative models, we found a commonly abnormal pattern of GMV asymmetry across all ASD children: more rightward laterality in the inferior parietal lobe and precentral gyrus, and higher individual variability in the temporal pole. Specifically, ASD with DD/ID children showed a severer and more extensive abnormal pattern in GMV asymmetry deviation values, which was linked with both ASD symptoms and verbal IQ. The abnormal pattern of ASD without DD/ID children showed higher and more extensive individual variability, which was linked with ASD symptoms only. DD/ID children showed no significant differences from healthy population in asymmetry. Lastly, the GMV laterality patterns of all patient groups were significantly associated with both shared and unique gene expression profiles. Our findings provide evidence for rightward GMV asymmetry of some cortical regions in young ASD children (1–7 years) in a large sample (1030 cases), show that these asymmetries are related to ASD symptoms, and identify genes that are significantly associated with these differences.

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Fig. 1: Overview of the multi-scale cascade.
Fig. 2: The GMV asymmetry deviations in the three patient groups.
Fig. 3: Comorbidities between patient groups.
Fig. 4: The identified canonical modes linking GMV asymmetry deviations and behavioural performance in ASD children without DD/ID and ASD children with DD/ID.
Fig. 5: Associations characterized by interregional similarities between gene expression profiles and GMV asymmetry deviations of patient groups.
Fig. 6: Functional enrichment of GMV asymmetry-related multiple gene lists from ASD children with DD, ASD children without DD and children with DD only.

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Data availability

Access to the identified participant research data must be approved by the research ethics board on a case-by-case basis, please contact the corresponding authors (feili@shsmu.edu.cn, mcao@fudan.edu.cn) for assistance in data access request.

Code availability

The code for spatial autocorrelation-preserving permutation test is available at (https://github.com/frantisekvasa/rotate_parcellation) (version 3, June 2022). All home developed codes will be given on request.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81901826, 61932008, 62076068, 82271627, 82125032, 81930095, 81761128035, 82202243, and 82204048), the Science and Technology Commission of Shanghai Municipality (23Y21900500, 19410713500 and 2018SHZDZX01), the Shanghai Municipal Commission of Health and Family Planning (GWVI-11.1-34,GWV-10.1-XK07, 2020CXJQ01, 2018YJRC03), the Shanghai Clinical Key Subject Construction Project (shslczdzk02902), the Shanghai Municipal Science and Technology Major Project [2021ZD0200800,No.2018SHZDZX01], Innovative research team of high-level local universities in Shanghai (SHSMU-ZDCX20211100), the Guangdong Key Project (2018B030335001), the Shanghai Municipal Commission of Health and Family Planning (20214Y0125), the National Key R&D Program of China (grant numbers 2018YFC1312900 and 2019YFA0709502), and the ZJ Lab, Shanghai Center for Brain Science and Brain-Inspired Technology and the 111 Project (grant number B18015).

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Authors and Affiliations

  1. Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China

    Shujie Geng, Edmund T. Rolls, Yue Zhang, Jianfeng Feng & Miao Cao

  2. Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, China

    Shujie Geng, Yue Zhang, Jianfeng Feng & Miao Cao

  3. Developmental and Behavioral Pediatric Department & Child Primary Care Department, Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yuan Dai, Yuqi Liu, Lin Deng, Zilin Chen & Fei Li

  4. Department of Computer Science, University of Warwick, Coventry, UK

    Edmund T. Rolls

  5. Oxford Centre for Computational Neuroscience, Oxford, UK

    Edmund T. Rolls

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  1. Shujie Geng
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Contributions

MC, FL and SG designed the study. YD, YL, YZ, LD, ZC contributed to the acquisition of research data. SG and MC conducted the data analysis. FL, MC, and SG provided the interpretation of results. MC and SG wrote the first draft of the manuscript. ETR and JF revised the manuscript.

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Correspondence to Fei Li or Miao Cao.

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The study was conducted in compliance with the declaration of Helsinki, approved by the Ethics Committee of Xinhua Hospital affiliated with the Shanghai Jiao Tong University School of Medicine (XHEC-C-2019-076) and registered with ClinicalTrials.gov (NCT04358744). The legal guardian of all participants signed the written informed consent after detailed information notification.

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Geng, S., Dai, Y., Rolls, E.T. et al. Rightward brain structural asymmetry in young children with autism. Mol Psychiatry 30, 2860–2870 (2025). https://doi.org/10.1038/s41380-025-02890-9

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