Autism and Prenatal Endocrine Disruptors (A-PED)

自闭症和产前内分泌干扰物 (A-PED)

基本信息

批准号：
10006730
负责人：
ABRAHAM REICHENBERG
金额：
$ 57.99万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10006730
关键词：
Address Affect Archives Biometry Birth Blood specimen Chemical Exposure Chemicals Child Childhood Clinical Data Diagnostic Endocrine Disruptors Environment Environmental Epidemiology Environmental Exposure Environmental Risk Factor Epidemiology Epigenetic Process Etiology Exposure to Female Foundations Future Gender Genetic Genomics Gestational Age Glutamates Goals Government Healthcare Systems Individual Individual Differences Intellectual functioning disability Investigation Joints Link Measures Medical Neurodevelopmental Disorder Outcome Study Pathway interactions Patients Perinatal Phenotype Polychlorinated Biphenyls Population Population-Based Registry Pregnancy Preventive Psychiatric epidemiology Research Research Personnel Research Priority Resources Risk Risk Factors Role Sample Size Sampling Serum Severities Severity of illness Sex Differences Social Behavior Strategic Planning Sum Sweden Therapeutic Universities Update autism spectrum disorder autistic children biobank boys clinical heterogeneity cohort communication behavior disorder risk early pregnancy environmental chemical exposed human population gamma-Aminobutyric Acid genome-wide girls high risk population male maternal serum medical schools modifiable risk neurodevelopment neurotransmission novel organochlorine pesticide phthalates polybrominated diphenyl ether population based prenatal prenatal exposure repetitive behavior sex

项目摘要

PROJECT SUMMARY Autism and spectrum disorders (ASD) are serious and debilitating neurodevelopmental disorders that incur substantial suffering for patients and major challenges to our health care system. It is now estimated that ASD affects about 1 in 68 children, with a male:female ratio of 4:1. Both genetic and environmental factors contribute to ASD, but environmental factors have been understudied. Because environmental factors are potentially modifiable they should be a research priority. This effort has been hampered by the challenges of acquiring accurate and relevant exposure measures in large, unbiased, epidemiologic cohorts. Among the many environmental exposures to which humans are exposed, endocrine disrupting chemicals (EDs) have perhaps the best-known effects on neurodevelopment in pediatric populations. Several of these chemicals, particularly when exposure is prenatal, have been linked to autism-related phenotypes, and sex- differences in these associations have been documented. EDs have been shown to affect GABA and glutamate neurotransmission, which have prominent roles in ASD. Therefore, EDs are promising candidates as environmental triggers for ASD. To our knowledge, no prior study has been able to robustly link prenatal ED exposure to ASD. The goal of this application is to determine whether prenatal exposure to five classes of EDs impacts ASD risk. To achieve this, we will use stored samples from a serum biobank in southern Sweden and link these to population-based registries that include individual-level perinatal, diagnostic, medical, and demographic information (117,318 births in the years 1998-2007). We will randomly select and validate 600 ASD cases (oversampling females to include 200 females, 400 males) and 600 controls with similar sex and birth year distributions. By measuring concentrations of 38 EDs in five chemical classes in maternal serum samples we will address the following three integrated specific aims: First, determine the associations between ASD risk and prenatal serum concentration of our target EDs and their mixtures; Second, determine whether gender modifies sensitivity to prenatal ED exposure resulting in sex-dimorphic ED-ASD associations; Third, determine whether concentrations of EDs, singly and in combination, contribute to differences in ASD phenotype and their severity.

项目概要自闭症和谱系障碍 (ASD) 是严重且使人衰弱的神经发育障碍，会导致患者遭受巨大痛苦，我们的医疗保健系统面临重大挑战。现在估计ASD 大约每 68 名儿童中就有 1 人受到影响，男女比例为 4:1。遗传和环境因素都有有助于自闭症谱系障碍（ASD），但环境因素尚未得到充分研究。因为环境因素是潜在的可修改性应该成为研究的重点。这项努力受到以下挑战的阻碍在大型、公正的流行病学队列中获取准确且相关的暴露测量。在人类接触的众多环境暴露中，内分泌干扰化学物质（ED）对儿科人群神经发育的影响可能是最著名的。其中几个化学物质，特别是在产前接触化学物质时，已与自闭症相关表型和性别有关。这些关联的差异已被记录。 ED 已被证明会影响 GABA 和谷氨酸神经传递，在 ASD 中发挥着重要作用。因此，ED 是有希望的候选人 ASD 的环境诱因。据我们所知，之前没有研究能够将产前 ED 与产前 ED 强有力地联系起来。暴露于 ASD。本应用的目标是确定产前接触五类 ED 是否会影响 ASD 风险。为了实现这一目标，我们将使用瑞典南部血清生物库中存储的样本，并将这些样本链接到基于人群的登记，包括个人层面的围产期、诊断、医疗和人口统计信息（1998-2007 年出生 117,318 人）。我们将随机选择并验证 600 个 ASD 案例（对女性进行过采样，包括 200 名女性、400 名男性）和 600 名具有相似性别和出生年份的对照分布。通过测量母体血清样本中 5 种化学类别的 38 种 ED 浓度，我们将解决以下三个综合具体目标：首先，确定 ASD 风险之间的关联我们的目标 ED 及其混合物的产前血清浓度；二、判断是否性别改变对产前 ED 暴露的敏感性，导致性别二态性 ED-ASD 关联；三、确定 ED 的浓度（单独或组合）是否会导致 ASD 表型的差异以及他们的严重性。