Metals Dysregulation, Brain Development, and Autism Spectrum Disorder

摘要 这项研究的目的是研究产前和早期接触金属对发育的影响。 大脑、认知和适应功能以及自闭症谱系障碍(ASD)。自闭症行为的展开 在童年的头几年，伴随着不同年龄的大脑变化 患有自闭症的儿童和具有典型发展轨迹的儿童。患有自闭症儿童的婴儿兄弟姐妹在 ASD的风险增加了近5倍，近60%的人经历了神经发育延迟，这使得 ASD婴儿的家庭危险(HR)模型是研究早期脑发育和 表现出早期生活行为的特征。然而，许多现有人口的最初目标是拥有丰富的 神经成像、认知、行为和ASD数据通常不包括环境的影响。新的 需要环境暴露评估方法来利用这些现有的有价值的人口。 利用大棚乳牙的发育特性和基于激光的采样方法，我们可以 测量从怀孕中期到寿命第一年的金属暴露强度和时间 曝光。重金属既是公认的神经毒物，也是必需的营养物质。在此，我们建议 胎儿期和早产期金属暴露与脑部纵向测量的关系 自闭症谱系障碍丰富风险中的发育、认知和适应功能与ASD风险 (ASD-ER)环境对儿童健康结局的影响(ECHO)队列(OD023342)。ASD-ER 由13个地点组成，每个地点都登记了HR婴儿，并对36个月大的婴儿进行了纵向跟踪。 然后联系了这些参与者，并要求他们提供脱落式乳牙。这样做的具体目的是 研究的目的是：(1)研究产前和早期接触金属对自闭症和自闭症发生的影响。 维度ASD表型；(2)评估产前和早期接触金属对早期ASD的影响 认知发展和适应功能的轨迹；(3)研究产前和早期的影响 生命金属暴露对早期纵向脑发育的影响。因为暴露在神经毒性金属中可能会 这项研究的潜在公共健康影响是巨大的。 此外，在幼儿中识别危险因素为早期干预提供了机会。 在那里，仍有可能降低无序发展的风险。

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.