Zhang Yong, Xie Fang, Li Sheng, Li Ying, Yang Liting, Wang Zhen, Lei Jinlin, Guo Huailan
School of Public Health, Hubei University of Medicine, Shiyan, China.
Research Center of Environment and Health of South-to-North Water Diversion Area, Hubei University of Medicine, Shiyan, China.
Autism Res. 2025 Feb;18(2):427-436. doi: 10.1002/aur.3302. Epub 2024 Dec 27.
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.
几种与抗氧化功能相关的微量元素失衡可能导致自闭症谱系障碍（ASD）相关的生理功能障碍。尽管如此，关于这些元素与ASD之间的联系仍存在矛盾的结果，并且对它们的联合效应和相互作用的研究也不足。因此，我们设计了一项病例对照研究，纳入152名ASD儿童和152名年龄和性别匹配的发育正常（TD）儿童，以探讨锰（Mn）、锌（Zn）、铜（Cu）和硒（Se）与ASD的个体和联合关联。与TD儿童相比，ASD儿童的Zn和Se水平较低，Cu水平较高。受限立方样条模型显示Mn、Zn、Cu与ASD之间存在J形非线性、L形非线性和正线性相关性。Zn和Cu分别与ASD症状呈负相关和正相关。超氧化物歧化酶（SOD）分别介导了Zn、Se与ASD之间50.53%和39.07%的关联。贝叶斯核机器回归（BKMR）证实了元素混合物与ASD之间呈U形相关性。还观察到Mn与其他三种元素以及Cu与Zn之间的相互作用。我们的结果证实，四种微量元素的独立暴露和联合暴露均与ASD相关，氧化应激是一个重要机制。由于元素之间可能存在相互作用，需要进一步研究从联合角度探讨它们在ASD发病机制和进展中的作用，以及有益和有害的浓度范围。
