Neurodevelopmental Effects of Perfluorinated Chemicals

摘要 这一建议建立在候选人的论文研究的基础上，该研究考察了产前与 暴露于全氟化学品和三种特定的神经发育结果，包括 丹麦国家出生队列(DNBC)中的自闭症、注意力缺陷/多动障碍和脑瘫 这包括大约10万名母亲和儿童。全氟碳化物是广泛存在的持久性有机污染物， 孕妇和胎儿经常不由自主地几乎无处不在地接触到这些合成的 自20世纪50年代以来的化合物。动物研究表明，全氟化碳是发育毒物，但证据来自 对人类的研究很少。加州大学洛杉矶分校和奥胡斯大学长达十年的合作使 有资格获得独特的、大规模的、全国性的丹麦队列和登记册进行研究的候选人。这个 拟议的研究将极大地扩大DNBC和各种丹麦登记册的使用，并允许第一次 产前PFC暴露与一系列神经发育结果之间联系的时间检查 以前从未进行过研究，包括(1)对智力、认知、 5岁儿童的注意力、记忆力和运动技能；(2)医院诊断为癫痫；(3)儿童的社交能力 11岁时的能力和心理健康；以及(4)16岁以下的智力能力和学习表现。 拟议的研究将利用储存的孕妇怀孕血液样本这一宝贵资源。 来自DNBC的数据，允许对胎儿发育期间PFC暴露水平进行可靠和有效的评估。 该提案将在加州大学洛杉矶分校之间正在进行的强有力的合作的背景下进行 流行病学系和奥胡斯大学，增加了来自加州大学洛杉矶分校医疗心理学的新合作伙伴 评估中心(MPAC)和人类遗传学系。这个应用程序建立在刘博士的 在环境科学和先进的流行病学方法方面的专业知识。这将使他获得新的 在临床心理学、环境统计学和神经行为表观/遗传学方面的必要培训，并建立 与进行未来尖端表观基因/环境相互作用研究相兼容的技能组合 最佳利用北欧国家现有的大型生物样本库。比亚特·里茨博士和约恩·奥尔森博士 已同意通过K99流程指导候选人。罗伯特·阿萨诺博士将在 使用/评分复杂的神经心理学工具和神经精神病学的临床知识 精神错乱。Michael Jerrett博士将提供环境统计和暴露方面的培训机会 评估被称为“外部暴露”。Steve Horvath博士将提供高级培训 基因-环境与表观遗传网络分析。此应用程序的内容提供了一种策略 定位候选人以成功进入终身教授轨道职位，并为他配备 走向独立和执行R01提案所需的技能。

ABSTRACT This proposal builds on the candidate’s dissertation research that examined the associations between prenatal exposure to perfluorinated chemicals (PFCs) and three specific neurodevelopmental outcomes, including autism, attention-deficit/hyperactivity disorder, and cerebral palsy in the Danish National Birth Cohort (DNBC) that consists of ~100,000 mothers and children. PFCs are widespread persistent organic pollutants, and pregnant women and fetuses are often involuntarily and nearly ubiquitously exposed to these synthetic compounds since the 1950s. Animal studies suggest that PFCs are developmental toxicants but evidence from human studies is sparse. Decade long collaborations between UCLA and Aarhus University enabled the candidate to gain access to the unique, large-scale, nationwide Danish cohorts and registries for research. The proposed study will greatly expand the use of DNBC and various Danish registers and allow for the very first time examination of the link between prenatal PFC exposures and an array of neurodevelopmental outcomes never investigated before, including (1) extensive neuropsychological assessments of intelligence, cognition, attention, memory and motor skills in children at age 5; (2) hospital diagnosis of epilepsy; (3) the child’s social competence and mental health at age 11; and (4) intellectual capacity and school performance up to age 16. The proposed studies will capitalize upon the valuable resource of stored maternal pregnancy blood samples from DNBC, allowing a reliable and valid assessment of PFC exposure levels during fetal development. The proposal will be pursued within the context of a strong ongoing collaboration between the UCLA Department of Epidemiology and Aarhus University, adding new partners from the UCLA Medical Psychology Assessment Center (MPAC) and Department of Human Genetics. This application builds on Dr. Liew’s expertise in environmental sciences and advanced epidemiologic methods. It will allow him to newly gain the necessary training in clinical psychology, environmental statistics, and neurobehavioral epi/genetics and to build a skillset compatible with conducting future cutting-edge epi-gene/environment interactions research that optimally uses existing large bio-sample repositories in the Nordic countries. Drs. Beate Ritz and JØrn Olsen have agreed to mentor the candidate through the K99 process. Dr. Robert Asarnow will provide training in administrating/scoring complex neuropsychological instruments and clinical knowledge of neuropsychiatric disorders. Dr. Michael Jerrett will provide training opportunities in environmental statistics and exposure assessment referred to as the ‘external exposome’. Dr. Steve Horvath will provide training in advanced gene-environment and epigenetic network analysis. The contents of this application provide a strategy to position the candidate to successfully launch into a tenured professor track position and equip him with the necessary skills to move towards independence and pursue R01 proposals.