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、多动症和对立障碍）已被确定为青少年犯罪和后来的成人暴力的危险因素。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结果。然而，目前尚不清楚这种影响是否持续，或者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初步分析的证据，我们建议研究学龄前铅暴露对青春期早期外化行为的中介机制。假设铅暴露会引起两种相关症状，认知障碍（低智商，P300事件相关电位降低，学习成绩差）和情绪失调（低迷走神经张力，低唤醒和低应激反应），这反过来形成了儿童外化行为的机制途径。这个新的R01建立在PI当前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。我们建议在重复测量血铅、智商、行为、学校表现和青春期前心理社会风险因素的基础上，增加新的神经认知和情感测量（估计N = 1200）。采用结构方程模型检验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。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。研究结果对理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，本研究可能为降低当前cdc定义的安全铅含量提供策略，并减少神经认知缺陷和行为问题的可能性。最终，它将潜在地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. PUBLIC HEALTH RELEVANCE: Understanding the neurobiological basis of lead exposure on children's externalizing behavior will be significant to future attempts to tackle two important global public health issues: lead exposure and children externalizing behavior, ultimately helping to improve the quality life of the individual and the family unit.