Altered Neurite Microstructure and Trace Element Imbalance in Children With Autism Spectrum Disorder and Language...

Autism spectrum disorder (ASD) is a neurodevelopmental condition of complex etiology. Although not a core diagnostic feature, many children with ASD show language delay (LD) early on. In this study, we investigated changes in trace elements (lead [Pb] and iron [Fe]) and neurite microstructure via neurite orientation dispersion and density imaging (NODDI) and their relationships with language phenotypes.

This study included 105 children with ASD and LD (ASD-LD), 107 with ASD without LD (ASD-nLD), and 108 typically developing (TD) children. NODDI magnetic resonance imaging quantified intracellular volume fraction (ICVF), isotropic volume fraction (ISOVF), and orientation dispersion index (ODI) of 76 nuclei or brain regions. Serum Fe and Pb were measured. Multivariate analyses and mediation models examined group differences, element-structure correlations, and pathways affecting language function.

The ASD-LD group showed decreased ICVF and ODI in language regions, including the superior, middle, and inferior temporal gyrus, the inferior parietal lobule, and the precuneus. Serum Fe was lower and Pb was higher in children in the ASD-LD group compared with both the ASD-nLD and TD groups (p < .001). Specifically, in the ASD-LD group, ODI values in key language-related brain regions correlated positively with Fe levels and negatively with Pb levels. Mediation analysis indicated that Fe deficiency influenced LD both directly and indirectly through reduced ODI.

Children with ASD-LD exhibit impaired neurite microstructure in the language region, characterized by reduced ICVF, ISOVF, and ODI, alongside a low Fe-high Pb imbalance. Fe deficiency affected language function by lowering ODI, while elevated Pb may exacerbate neurite simplification. Results underscore trace element-neurite microstructure interplay in ASD-LD.