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<p>Autism spectrum disorder (ASD) is a commonly associated behavioral diagnosis in individuals with fragile X syndrome (FXS). The present study aimed to identify the neuroanatomical profiles and the age effects on brain’s developing trajectories that might be distinct or shared in FXS and idiopathic ASD. A total of 190 children were consecutively recruited including 46 with FXS (5.39 ± 2.68 years), 90 with idiopathic ASD (3.38 ± 1.36 years), and 54 typically developing children (5.40 ± 2.90 years). T1-weighted structural magnetic resonance imaging scans of the brain were acquired, and behavioral assessments were collected from all participants. Age-varying, voxel-based morphometry (VBM) was conducted to identify neuroanatomical differences between groups. The most pronounced differences in brain morphological patterns were observed in the FXS group. Children with FXS had increased gray matter volume (GMV) in subcortical regions including caudate and Crus I of the cerebellum, but decreased GMV in frontal insular regions and cerebellar vermis lobules VIII/IX compared to the ASD and TD groups. Children with ASD had significantly faster growth rates of GMV. The identified neuroanatomical profiles correlated with behavior assessments and differed between diagnosis groups. Our findings suggest that FXS and ASD have distinct neuroanatomical signatures during early childhood, particularly in subcortical and cerebellar regions, which are associated with divergent developmental trajectories. Together with their distinct brain-behavior associations, we conclude that these two conditions have distinct neurobiological underpinnings at spatial and temporal scales, despite their overlapping clinical symptoms. These findings have important implications for diagnosis and targeted interventions for children with ASD and FXS.</p>

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Age-varying distinct neuroanatomy in young children with autism spectrum disorder and fragile X syndrome

  • 期刊论文

  • 发表日期：

    2025年11月14日

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  • Danyong Feng,
  • Dongyun Li,
  • Chunchun Hu,
  • Yuxin Tian,
  • Xiu Xu,
  • Randi Jenssen Hagerman,
  • Qiong Xu,
  • Rihui Li

摘要

Autism spectrum disorder (ASD) is a commonly associated behavioral diagnosis in individuals with fragile X syndrome (FXS). The present study aimed to identify the neuroanatomical profiles and the age effects on brain’s developing trajectories that might be distinct or shared in FXS and idiopathic ASD. A total of 190 children were consecutively recruited including 46 with FXS (5.39 ± 2.68 years), 90 with idiopathic ASD (3.38 ± 1.36 years), and 54 typically developing children (5.40 ± 2.90 years). T1-weighted structural magnetic resonance imaging scans of the brain were acquired, and behavioral assessments were collected from all participants. Age-varying, voxel-based morphometry (VBM) was conducted to identify neuroanatomical differences between groups. The most pronounced differences in brain morphological patterns were observed in the FXS group. Children with FXS had increased gray matter volume (GMV) in subcortical regions including caudate and Crus I of the cerebellum, but decreased GMV in frontal insular regions and cerebellar vermis lobules VIII/IX compared to the ASD and TD groups. Children with ASD had significantly faster growth rates of GMV. The identified neuroanatomical profiles correlated with behavior assessments and differed between diagnosis groups. Our findings suggest that FXS and ASD have distinct neuroanatomical signatures during early childhood, particularly in subcortical and cerebellar regions, which are associated with divergent developmental trajectories. Together with their distinct brain-behavior associations, we conclude that these two conditions have distinct neurobiological underpinnings at spatial and temporal scales, despite their overlapping clinical symptoms. These findings have important implications for diagnosis and targeted interventions for children with ASD and FXS.