Metals Dysregulation, Brain Development, and Autism Spectrum Disorder

摘要 本研究的目的是检查产前和生命早期金属暴露对发育中的 大脑、认知和适应功能以及自闭症谱系障碍（ASD）。自闭症行为的发展 在儿童的最初几年，伴随着年龄特定的大脑变化， 自闭症儿童和具有典型发展轨迹的儿童。ASD儿童的婴儿兄弟姐妹在 ASD的风险增加近5倍，近60%的人经历神经发育延迟， ASD婴儿的家族风险（HR）模型是研究早期大脑发育的一种有吸引力的方法， 早期生活行为的特征。然而，许多现有人口的最初目标， 神经成像、认知、行为和ASD数据通常不包括环境的影响。新 需要环境暴露评估方法来利用这些现有的宝贵人口。 利用脱落乳牙的发育特性和基于激光的采样方法，我们可以 测量从第二个三个月到第一年的金属暴露强度和时间 exposure.重金属是公认的神经毒物和必需营养素。在此，我们建议 检查产前和生命早期金属暴露与脑纵向测量之间的关系 自闭症谱系障碍风险增加患者的发育、认知和适应功能以及ASD风险 （ASD-ER）环境对儿童健康结局的影响（ECHO）队列（OD 023342）。ASD-ER 由13个研究中心组成，每个研究中心均招募了HR婴儿，并进行了36个月的纵向随访。 然后联系这些参与者并要求他们提供脱落的乳牙。具体目标是 研究的目的是：（1）检查产前和生命早期金属暴露对ASD发展的影响， （2）评估产前和生命早期金属暴露对早期ASD表型的影响。 认知发育和适应功能的轨迹;（3）探讨产前和早期干预对认知发育和适应功能的影响 生命金属暴露对早期脑纵向发育的影响因为暴露在神经毒性金属中 缓解和必需营养素的增加，这项研究的潜在公共卫生影响是巨大的。 此外，确定幼儿的危险因素为早期干预提供了机会 其中仍然可以降低无序发育的风险。

ABSTRACT The goal of this study is to examine the effect of prenatal and early life metals exposure on the developing brain, cognitive and adaptive function, and autism spectrum disorder (ASD). The unfolding of autistic behaviors across the first few years of childhood is accompanied by age-specific brain changes that differ between children with ASD and those with typical developmental trajectories. Infant siblings of children with ASD are at a nearly 5-fold increased risk for ASD, and nearly 60% experience neurodevelopmental delay, making a high familial risk (HR) model of ASD infants an attractive approach for studying early brain development and characterizing early life behavior. However, the initial goal of many existing populations with a wealth of neuroimaging, cognitive, behavior, and ASD data has not often included the effect of the environment. New methods of environmental exposure assessment are needed to leverage these existing valuable populations. Using the developmental properties of shed deciduous teeth and laser-based sampling methods, we can measure both the intensity and timing of exposure from the second trimester to the first year of life for metals exposure. Heavy metals are both established neurotoxicants and essential nutrients. Here we propose to examine the relationship between prenatal and early life metals exposure and longitudinal measures of brain development, cognitive and adaptive function, and ASD risk in the Autism Spectrum Disorder Enriched Risk (ASD-ER) Environmental Influences on Children's Health Outcomes (ECHO) cohort (OD023342). ASD-ER consists of 13 sites, each having enrolled HR infants with longitudinal follow-up through 36 months of age. These participants were then contacted and asked to provide shed deciduous teeth. The Specific Aims of this study are to: (1) examine the effect of prenatal and early life metals exposure on the development of ASD and dimensional ASD phenotypes; (2) evaluate the effect of prenatal and early life metals exposure on the early trajectory of cognitive development and adaptive function; and (3) investigate the effect of prenatal and early life metals exposure on early longitudinal brain development. Because exposure to neurotoxic metals can be mitigated and that to essential nutrients be augmented, the potential public health impact of this study is large. Additionally, identification of a risk factor in very young children provides the opportunity for early intervention where reduction of risk for disordered development is still possible.