Metals Dysregulation, Brain Development, and Autism Spectrum Disorder

金属失调、大脑发育和自闭症谱系障碍

基本信息

批准号：
10327338
负责人：
Paul Curtin
金额：
$ 59.39万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
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/10327338
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

项目摘要

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最初几年里，伴随着特定年龄的大脑变化，这些变化在不同年龄段之间有所不同患有 ASD 的儿童和具有典型发展轨迹的儿童。自闭症儿童的婴儿兄弟姐妹在患自闭症谱系障碍 (ASD) 的风险增加了近 5 倍，并且近 60% 的人经历过神经发育迟缓，这使得 ASD 婴儿的家族风险 (HR) 模型是研究早期大脑发育和发育的一种有吸引力的方法表征早期生活行为。然而，许多拥有丰富财富的现有人口的最初目标神经影像、认知、行为和自闭症谱系障碍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宝贵人群。利用脱落乳牙的发育特性和基于激光的采样方法，我们可以测量从妊娠中期到生命第一年的金属暴露强度和时间接触。重金属既是既定的神经毒物，又是必需的营养素。在此我们建议检查产前和生命早期金属暴露与大脑纵向测量之间的关系自闭症谱系障碍丰富风险中的发育、认知和适应功能以及 ASD 风险 (ASD-ER) 环境对儿童健康结果的影响 (ECHO) 队列 (OD023342)。 ASD-ER 由 13 个中心组成，每个中心都招募了 HR 婴儿，并进行了 36 个月大的纵向随访。然后联系这些参与者并要求他们提供脱落的乳牙。本次活动的具体目标研究的目的是：（1）检查产前和生命早期金属暴露对自闭症谱系障碍（ASD）和维度 ASD 表型； (2)评估产前和生命早期金属暴露对早期的影响认知发展和适应功能的轨迹； (3) 调查产前和早期干预的效果生命金属暴露对早期纵向大脑发育的影响。因为接触神经毒性金属可能会减轻并增加必需营养素，这项研究对公共健康的潜在影响是巨大的。此外，识别幼儿的危险因素为早期干预提供了机会仍然有可能降低无序发展的风险。