Autism and Prenatal Endocrine Disruptors (A-PED)

自闭症和产前内分泌干扰物 (A-PED)

• 批准号: 9349499
• 负责人: ABRAHAM REICHENBERG
• 金额: $ 60.63万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9349499
• 关键词: Address; Affect; Archives; Autistic Disorder; 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; Heterogeneity; Human; 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 Characteristics; Strategic Planning; Sum; Sweden; Therapeutic; Universities; Update; autism spectrum disorder; biobank; boys; cohort; disorder risk; environmental chemical; 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; social communication

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.

项目摘要 自闭症和频谱障碍（ASD）是严重的，令人衰弱的神经发育障碍 对患者的巨大痛苦以及我们的医疗保健系统的重大挑战。现在估计ASD 影响68名儿童中约1个，男性：女性比率为4：1。遗传和环境因素 有助于ASD，但已经研究了环境因素。因为环境因素是 潜在的修改应该是研究的重点。这项努力受到了挑战的阻碍 在大型，公正的流行病学人群中获得准确和相关的暴露措施。 在人类暴露的许多环境暴露中，内分泌破坏了化学物质 （ED）也许对小儿种群的神经发育有最著名的影响。其中几个 化学物质，尤其是在产前暴露时，与自闭症相关的表型和性别有关 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中具有突出的作用。因此，ED是有希望的候选人 环境触发ASD。据我们所知，没有先前的研究能够牢固地联系起来 暴露于ASD。 该应用程序的目的是确定产前接触五类EDS是否影响ASD风险。 为此，我们将使用瑞典南部血清生物库的储存样品，并将其链接到 基于人群的注册表，包括个人级别的围产期，诊断，医学和人口统计 信息（1998 - 2007年的117,318个出生）。我们将随机选择并验证600个ASD案例 （过度采样女性，包括200名女性，400名男性）和600个具有类似性别和出生年份的控制 分布。通过测量母体血清样品中五个化学类别中38个ED的浓度，我们 将解决以下三个集成特定目标：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；其次，确定性别是否 修饰对产前ED暴露的敏感性，导致性别二态ED-ASD关联；第三，确定 ED，单一和组合的浓度是否有助于ASD表型的差异和 他们的严重性。