Internalizing Behaviors and Neuroimaging Outcomes: Impact of PBDE and PFC Exposures

项目摘要/摘要 人类对环境污染物的暴露是无处不在的，人们越来越担心 其中一些可能与儿童神经行为问题的增加有关。鉴于缺乏确凿的结论 对于许多环境毒物的证据，迫切需要设计良好的纵向研究 产前和产后暴露，并进行长期跟踪，以解决有关以下影响的重点问题 这些化学物质，尤其是在神经行为终点处。我们将学习两节化学课，几乎 所有美国人都接触了多溴二苯醚(PBDEs)和全氟化学品 (全氟碳化物)，分别用作阻燃剂和表面活性剂。在一个既定的队列中 在健康结果和环境措施范围内典型地发展青春期前儿童 (家庭)研究，我们将确定产前和儿童时期接触这些持续性疾病之间的关系 污染物和内化行为，包括焦虑、抑郁和社会损害。我们还将获得 神经成像结果，以检查与暴露的关系。这项家庭研究招募了女性在 怀孕，到目前为止一直跟随后代直到8岁。我们将扩大跟进范围，包括在以下地点进行考察访问 11-12岁，研究青春期前的联系。产前暴露的测量使用母体 目前正在分析具有多个儿童样本的妊娠和新生儿样本。超过97%的 参与研究的妇女在怀孕期间可检测到多溴二苯醚和全氟化碳的水平；与全国水平相当 报告的水平。我们假设暴露在这些化学物质中会潜移默化地改变大脑产生 神经行为缺陷，将明显表现为内化症状的增加和 解剖结构、神经化学、白质束的组织和神经网络的连通性。 目的1：确定产前和儿童暴露于多溴二苯醚和全氟碳化合物对内化的影响 11-12岁儿童纵向出生队列中的症状。 目的2：确定产前和儿童期接触多溴二苯醚对大脑结构的影响。 在11-12岁儿童的纵向出生队列中，组织和功能。 探索性目标(EA)：确定产前和儿童期全氟化碳暴露对大脑的影响 11-12岁儿童纵向出生队列的结构、组织和功能。 目的3：确定脑结构、组织和功能在脑损伤中的潜在中介作用 产前和儿童期接触多溴二苯醚与内化症状的纵向关系 11-12岁儿童的出生队列。 目标4：确定适当的统计方法，以确定单一和多个之间的联系 PBDE和PFC暴露与多个发育阶段的神经发育有关。

Project Summary/Abstract Human exposure to environmental contaminants is ubiquitous, and there is growing concern that exposure to some may be linked with the rise in neurobehavioral problems in children. Given the lack of conclusive evidence for many environmental toxicants, there is a critical need for well-designed longitudinal studies of prenatal and postnatal exposure with long-term follow-up to address focused questions about the impact of these chemicals, especially on neurobehavioral endpoints. We will study two chemical classes to which nearly all of the US population are exposed, polybrominated diphenyl ethers (PBDEs) and perfluorinated chemicals (PFCs), that have been used as flame retardants and surfactants, respectively. Among an established cohort of typically developing pre-adolescent children within the Health Outcomes and Measures of the Environment (HOME) Study, we will determine associations between prenatal and childhood exposure to these persistent pollutants and internalizing behaviors including anxiety, depression and social impairment. We will also obtain neuroimaging outcomes to examine associations with exposure. The HOME Study enrolled women during pregnancy and has thus far followed offspring until age 8y. We will extend follow-up to include a study visit at 11-12y to study associations in the pre-adolescent period. Prenatal exposures were measured using maternal pregnancy and newborn specimens with multiple childhood samples currently being analyzed. Over 97% of participating women had detectable levels of PBDEs and PFCs during pregnancy; comparable with nationally reported levels. We hypothesize that exposures to these chemicals subtly alter the brain to produce neurobehavioral deficits that will be evident in increased internalizing symptoms and adverse changes in anatomical structure, neurochemistry, organization of white matter tracts, and connectivity of neural networks. Aim 1: To determine the impact of prenatal and childhood exposures to PBDEs and PFCs on internalizing symptoms in a longitudinal birth cohort of 11-12 year old children. Aim 2: To determine the impact of prenatal and childhood exposures to PBDEs on brain structure, organization, and function in a longitudinal birth cohort of 11-12 year old children. Exploratory aim (EA): To determine the impact of prenatal and childhood exposures to PFCs on brain structure, organization, and function in a longitudinal birth cohort of 11-12 year old children. Aim 3: To determine the potential mediational impact of brain structure, organization and function in the relationship between prenatal and childhood exposures to PBDEs and internalizing symptoms in a longitudinal birth cohort of 11-12 year old children. Aim 4: To identify appropriate statistical methodologies to determine the association of single and multiple PBDE and PFC exposures with neurodevelopment across multiple developmental stages.