Fetal and postnatal metal dysregulation in autism.
Fetal and postnatal metal dysregulation in autism.
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DOI：
10.1038/ncomms15493
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发表时间：
2017-06-01
影响因子：
16.6
通讯作者：
Bölte S
中科院分区：
文献类型：
--
作者：
Arora M;Reichenberg A;Willfors C;Austin C;Gennings C;Berggren S;Lichtenstein P;Anckarsäter H;Tammimies K;Bölte S
遗传和环境因素有助于自闭症谱系障碍（ASD）的病因，但具体的环境暴露和易感性窗口的证据是有限的。在这里，我们研究了同卵双胞胎和异卵双胞胎不一致的ASD，以测试是否胎儿和出生后的金属失调增加ASD的风险。使用经验证的牙齿基质生物标志物，我们估计出生前和出生后的暴露概况的基本和有毒元素。ASD病例和对照组兄弟姐妹之间的金属摄取存在明显差异，但仅在离散的发育期内。病例对必需元素锰和锌的摄取减少，对神经毒素铅的摄取增加。锰和铅也与ASD的严重程度和自闭症特征相关。我们的研究表明，在特定的发育窗口期，金属毒物摄取和必需元素缺乏会增加ASD的风险和严重程度，支持ASD中全身元素失调的假设。需要在以人群为基础的研究中进行独立的复制，以扩展这些发现。金属暴露对ASD病因的贡献尚不清楚。在这里，作者通过分析ASD不一致双胞胎的牙齿金属生物标志物来测试元素失调是否有助于ASD风险，并发现ASD病例与其对照双胞胎兄弟姐妹之间的金属摄取存在显着差异，但仅在某些发育时期。
Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings. The contribution of metal exposure to the etiology of ASD is unclear. Here the authors tested whether elemental dysregulation contributes to ASD risk by analysing tooth metal biomarkers from ASD discordant twins, and found significant differences in metal uptake between ASD cases and their control twin siblings, but only during certain developmental periods.