Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1057, New York, New York 10029, USA.
Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, New York 10029, USA.
Nat Commun. 2017 Jun 1;8:15493. doi: 10.1038/ncomms15493.
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.
遗传和环境因素共同导致了自闭症谱系障碍（ASD）的发生，但具体的环境暴露和易感窗口的证据有限。在这里，我们研究了在自闭症谱系障碍方面存在单卵双生子和双卵双生子差异的双胞胎，以检验胎儿和产后金属失调是否会增加自闭症谱系障碍的风险。我们使用经过验证的牙基质生物标志物来估计产前和产后必需元素和有毒元素的暴露情况。在自闭症谱系障碍病例与其对照兄弟姐妹之间，金属摄入存在明显差异，但仅在离散的发育时期存在差异。病例组摄入的必需元素锰和锌减少，而神经毒素铅的摄入增加。锰和铅也与自闭症谱系障碍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内，金属毒物摄入和必需元素缺乏会增加自闭症谱系障碍的风险和严重程度，支持了自闭症谱系障碍中系统性元素失调的假说。需要在基于人群的研究中进行独立的复制，以扩展这些发现。
