Associations of Serum Manganese, Zinc, Copper, and Selenium Concentrations With Autism Spectrum Disorders in Chinese Children: A Case–Control Study

Imbalances in several trace elements related to antioxidant function may lead to autism spectrum disorder (ASD)-related physiological dysfunction. Nonetheless, contradictory results have been found on the connection between these elements and ASD, and studies of their joint effects and interactions have been insufficient. We therefore designed a case-control study of 152 ASD children and 152 age- and sex-matched typically developing (TD) children to explore the individual and combined associations of manganese (Mn), zinc (Zn), copper (Cu), and selenium (Se) with ASD. Compared with TD, ASD has lower Zn and Se levels and higher Cu levels. The restricted cubic spline model showed J-shaped non-linearity, L-shaped non-linearity, and positive linearity correlations between Mn, Zn, Cu, and ASD. Zn and Cu were negatively and positively correlated with ASD symptoms, respectively. The superoxide dismutase (SOD) mediated 50.53% and 39.07% of the association between Zn, Se, and ASD, respectively. Bayesian kernel machine regression (BKMR) confirmed a U-shaped correlation between the element mixtures and ASD. Interactions of Mn with the other three elements and Cu with Zn were also observed. Our results confirm that the independent and combined exposure to the four trace elements was associated with ASD, with oxidative stress being an important mechanism. Due to the potential interactions between the elements, further research is needed to explore their involvement in the pathogenesis and progression of ASD from a combined perspective, as well as the beneficial and harmful concentration ranges.