Metals Dysregulation, Brain Development, and Autism Spectrum Disorder

金属失调、大脑发育和自闭症谱系障碍

• 批准号: 9884990
• 负责人: Paul Curtin
• 金额: $ 61.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9884990
• 关键词: Adaptive Behaviors; Address; Affect; Age; Age-Months; Area; Award; Behavior; Behavioral; Biological Markers; Brain; Categories; Chemicals; Child; Child Health; Childhood; Cognition; Cognitive; Collaborations; Collection; Corpus Callosum; Cross-Sectional Studies; Data; Dental; Development; Developmental Delay Disorders; Diffusion Magnetic Resonance Imaging; Dimensions; Early Intervention; Elements; Enrollment; Environment; Environmental Exposure; Environmental Risk Factor; Equation; Exposure to; Fiber; Fostering; Goals; Heavy Metals; Individual; Infant; Infrastructure; Intake; Intervention; Investments; Joints; Lasers; Lead; Lead levels; Learning; Life; Link; Liquid substance; Logistics; Manganese; Measures; Metal exposure; Metals; Methods; Modeling; Morphology; Nature; Needs Assessment; Neurotoxins; Nutrient; Outcome; Participant; Pathway interactions; Perinatal; Phenotype; Population; Problem behavior; Property; Public Health; Publications; Recording of previous events; Research; Resources; Risk; Risk Factors; Risk Reduction; Sampling; Second Pregnancy Trimester; Siblings; Site; Structure; Surface; Technology; Time; Time Study; Tooth structure; Twin Studies; Work; Zinc; autism spectrum disorder; autistic behaviour; autistic children; base; behavior measurement; brain behavior; brain volume; cognitive development; cohort; cost effective; data harmonization; deciduous tooth; disorder risk; early childhood; early life exposure; experience; fetal; follow-up; innovation; neuroimaging; neurotoxic; novel; postnatal; prenatal; prospective; temporal measurement; toxic metal; trait; white matter

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.

抽象的 这项研究的目的是检查产前和早期生命金属暴露对发展的影响 大脑，认知和适应性功能以及自闭症谱系障碍（ASD）。自闭症行为的发展 在童年的头几年中，伴随着特定年龄的大脑变化 患有ASD的儿童和典型发育轨迹的孩子。 ASD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，使高 ASD婴儿的家族风险（HR）模型一种研究早期大脑发育和 表征早期生活的行为。但是，许多现有人群的最初目标是 神经影像学，认知，行为和ASD数据通常不包括环境的影响。新的 需要进行环境暴露评估的方法来利用这些现有的宝贵人群。 使用脱落牙齿和基于激光的采样方法的发育特性，我们可以 测量从妊娠中期到金属第一年的暴露强度和时间 接触。重金属都是建立的神经毒性和必需营养素。在这里我们建议 检查产前和早期生命金属暴露与大脑纵向测量之间的关系 自闭症谱系障碍中的发展，认知和适应性功能以及ASD风险丰富了风险 （ASD-ER）环境对儿童健康成果（ECHO）队列的影响（OD023342）。 asd-er 由13个地点组成，每个地点都有在36个月大的纵向随访的HR婴儿中。 然后联系这些参与者，并要求提供落叶牙齿。这个特定的目的 研究是：（1）检查产前和早期生命金属暴露对ASD和ASD的发展的影响 尺寸ASD表型； （2）评估产前和早期生命金属对早期的影响 认知发展和适应功能的轨迹； （3）研究产前和早期的影响 生命金属在早期纵向大脑发育中的暴露。因为暴露于神经毒性金属可以是 缓解并增加了必不可少的养分，这项研究的潜在公共卫生影响很大。 此外，鉴定很小的孩子的危险因素为早期干预提供了机会 仍然有可能降低发育障碍的风险。