Lead exposure, externalizing behavior, and neurobiological mediating factors

描述（由申请人提供）：铅是一种已知的神经毒性金属，儿童外化行为（攻击性，ADHD和对立障碍）已被确定为青少年犯罪和成年后暴力的风险因素。有初步证据表明，即使在亚临床铅暴露水平，儿童经历负面的认知和行为结果。然而，目前尚不清楚这种影响是否持续或亚临床铅暴露影响的发病机制是如何形成的。基于我们在纵向队列研究中的初步分析证据，我们建议研究学龄前儿童铅暴露对青少年早期外化行为的中介机制。铅暴露被假设为引起两种相关症状，认知障碍（低智商、P300事件相关电位降低、学校表现差）和情绪失调（低迷走神经张力、低唤醒和低应激反应），这反过来又形成了儿童期外化行为的机械途径。 这个新的R 01建立在PI目前的NIEHS资助的K奖和正在进行的大型前瞻性队列研究的独特数据的基础上。最初的流行病学样本包括1,650名3-5岁的中国男孩和女孩，他们的血铅水平是在2004年获得的，他们的智商测试分数和行为测量在6岁时进行了评估。我们建议增加新的神经认知和情绪的措施，除了重复测量血铅，智商，行为，学校表现，和心理社会风险因素在青春期前几年（估计N =1,200）。结构方程模型将被用来测试早期铅暴露对后期外化行为的主效应、交互效应和中介效应。该跨学科研究团队在研究铅暴露、儿童行为问题、心理生理学和儿童心理健康方面拥有数十年的经验。研究结果具有潜在的理论和临床意义，了解症状的神经认知和情绪的影响，铅暴露对儿童的外化行为。通过将神经科学评估工具与流行病学和毒理学相结合，这项研究可能会为降低目前CDC定义的安全铅水平的策略提供信息，并减少神经认知缺陷和行为问题的可能性。最终，它将有可能最大限度地减少负面环境暴露对儿童心理健康的影响，从而改善他们今后一生的福祉。

DESCRIPTION (provided by applicant): Lead is a known neurotoxic metal, and child externalizing behavior (aggression, ADHD, and oppositional disorder) has been identified as a risk factor for adolescent delinquency and later adult violence. There is preliminary evidence that even at sub- clinical lead exposure levels, children experence negative cognitive and behavioral outcomes. However, it is still unclear whether such effects are sustained or how the pathogenesis of the effect of sub-clinical lead exposure is shaped. Based on the evidence from our preliminary analyses in a longitudinal cohort study, we propose to study the mediating mechanisms by which exposure to lead during the preschool years contribute to externalizing behavior in early adolescence. Lead exposure is hypothesized to give rise to two related symptoms, cognitive impairment (low IQ, reduced P300 event- related potentials, poor school performance) and emotion dysregulation (low vagal tone, low arousal, and low stress reactivity) which in turn form the mechanistic pathway to childhood externalizing behavior. This new R01 builds on the PI's current NIEHS-funded K award and unique data from an on-going large prospective cohort study. The initial epidemiological sample consisted of 1,650 3-5 year-old Chinese boys and girls whose blood lead levels were obtained in 2004, and their IQ test scores and behavioral measures were assessed at age 6 years. We propose to add new neurocognitive and emotion measures in addition to repeating measures of blood lead, IQ, behavior, school performance, and psychosocial risk factors during preadolescent years (estimate N =1,200). Structural equation modeling will be used to test the main effect, interactive and mediating effects of early lead exposure on later externalizing behavior. The interdisciplinary research team has decades of experience in studying lead exposure, child behavior problems, psychophysiology, and child mental health. Findings have potential theoretical and clinical implications for understanding the symptoms of neurocognitive and emotional effects of lead exposure on children's externalizing behavior. By integrating neuroscience assessment tools with epidemiology and toxicology, this study could potentially inform strategies for lowing current CDC-defined safe lead levels, and reduce the likelihood of neurocognitive deficits and behavior problems. Ultimately it will potentially minimize the impact of negative environmental exposures on children's mental health, thus improving their subsequent well-being over the life-course.