Lead exposure, externalizing behavior, and neurobiological mediating factors

描述(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后来的成人暴力的风险因素。有初步证据表明，即使在亚临床铅暴露水平，儿童也会经历负面的认知和行为后果。然而，目前仍不清楚这种影响是否持续，也不清楚亚临床铅暴露的影响是如何形成的。根据我们在纵向队列研究中初步分析的证据，我们建议研究学龄前几年铅暴露对青春期早期外化行为的中介机制。据推测，铅暴露会导致两种相关症状，认知障碍(智商低，P300事件相关电位降低，学习成绩差)和情绪失调(迷走神经紧张性低，唤醒能力低，压力反应性低)，这反过来又形成儿童外化行为的机械途径。这一新的R01建立在PI目前由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1650名3~5岁的中国男孩和女孩，他们于2004年获得血铅水平，并在6岁时评估他们的智商测试分数和行为测量。我们建议增加新的神经认知和情绪测量，除了重复测量青春期前的血铅、智商、行为、学习成绩和心理社会风险因素(估计N=1,200)。结构方程模型将被用来检验早期铅暴露对后期外化行为的主效应、交互作用和中介效应。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。研究结果对于了解铅暴露对儿童外化行为的神经、认知和情绪影响的症状具有潜在的理论和临床意义。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疾控中心定义的安全铅水平的策略提供参考，并减少神经认知缺陷和行为问题的可能性。最终，它可能会将负面环境暴露对儿童心理健康的影响降至最低，从而改善他们随后在一生中的福祉。

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.