Identification and multidimensional characterization of two distinct autism spectrum disorder subtypes
- 1College of Electrical Engineering, Sichuan University, Chengdu, 610065 China
- 2School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054 China
- 3The Clinical Hospital of Chengdu Brain Science Institute, Chengdu, China
Abstract
Autism spectrum disorder (ASD) shows high variability in brain structure and behavior, complicating identification of biologically meaningful subtypes and their neuroanatomical and molecular bases. To address this, we analyzed structural MRI data from 1055 ASD and 1164 typically developing (TD) individuals. Gray matter volume (GMV) values from regions showing significant ASD–TD differences were extracted in ASD participants and used for supervised affinity propagation (AP) clustering. Subtypes were then characterized via individual differential structural covariance networks (IDSCN), followed by gene set enrichment analysis (GSEA) based on spatial transcriptomic data from the Allen Human Brain Atlas (AHBA) to identify molecular pathways associated with subtype-specific spatial GMV patterns. This integrative analysis identified two ASD subtypes with distinct neuroanatomical and molecular features. Subtype 1 showed widespread GMV reductions in social, limbic, and salience networks, reduced structural covariance, and enrichment in genes linked to neurodevelopment, neuronal differentiation, and synaptic organization. In contrast, Subtype 2 exhibited GMV increases in similar regions, stronger covariance, and enrichment in pathways involving cytoplasmic translation, mitochondrial organization, and synaptic signaling. These structural and molecular differences were also associated with variations in clinical symptom severity. Our findings reveal two ASD subtypes with distinct cortical morphometry, network patterns, and associated molecular signatures, emphasizing multiple neurodevelopmental paths and the value of biologically informed subtyping for precise diagnosis and personalized treatment.
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BibTeX
@article{zhang2026identification,
title = {{Identification and multidimensional characterization of two distinct autism spectrum disorder subtypes}},
author = {Heng Zhang and Tianwei Qin and Yiran Zhai and Jinming Xiao and Fengmei Lu and Jiang Zhang},
journal = {Translational Psychiatry},
year = {2026},
month = aug,
doi = {10.1038/s41398-026-04357-z},
url = {https://doi.org/10.1038/s41398-026-04357-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Identification and multidimensional characterization of two distinct autism spectrum disorder subtypes
AU - Heng Zhang
AU - Tianwei Qin
AU - Yiran Zhai
AU - Jinming Xiao
AU - Fengmei Lu
AU - Jiang Zhang
PY - 2026
DA - 2026/08/07
JO - Translational Psychiatry
DO - 10.1038/s41398-026-04357-z
UR - https://doi.org/10.1038/s41398-026-04357-z
AB - Autism spectrum disorder (ASD) shows high variability in brain structure and behavior, complicating identification of biologically meaningful subtypes and their neuroanatomical and molecular bases. To address this, we analyzed structural MRI data from 1055 ASD and 1164 typically developing (TD) individuals. Gray matter volume (GMV) values from regions showing significant ASD–TD differences were extracted in ASD participants and used for supervised affinity propagation (AP) clustering. Subtypes were then characterized via individual differential structural covariance networks (IDSCN), followed by gene set enrichment analysis (GSEA) based on spatial transcriptomic data from the Allen Human Brain Atlas (AHBA) to identify molecular pathways associated with subtype-specific spatial GMV patterns. This integrative analysis identified two ASD subtypes with distinct neuroanatomical and molecular features. Subtype 1 showed widespread GMV reductions in social, limbic, and salience networks, reduced structural covariance, and enrichment in genes linked to neurodevelopment, neuronal differentiation, and synaptic organization. In contrast, Subtype 2 exhibited GMV increases in similar regions, stronger covariance, and enrichment in pathways involving cytoplasmic translation, mitochondrial organization, and synaptic signaling. These structural and molecular differences were also associated with variations in clinical symptom severity. Our findings reveal two ASD subtypes with distinct cortical morphometry, network patterns, and associated molecular signatures, emphasizing multiple neurodevelopmental paths and the value of biologically informed subtyping for precise diagnosis and personalized treatment.
SN - 2158-3188
ER -