Lead exposure, externalizing behavior, and neurobiological mediating factors

铅暴露、外化行为和神经生物学中介因素

基本信息

批准号：
8265069
负责人：
JIANGHONG LIU
金额：
$ 1.14万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-08 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8265069
关键词：
11 year old 5 year old 6 year old Accounting Achievement Adolescent Adult Affective Age Aggressive behavior Arousal Attention deficit hyperactivity disorder Behavior Behavioral Biological Biosocial Boxing Brain Centers for Disease Control and Prevention (U.S.)Child Child Behavior Child Malnutrition Child Mental Health Childhood China Chinese People Cities Clinical Cognition Cognitive Cognitive deficits Cohort Studies Communities Community Networks Control Groups Cross-Sectional Studies Data Data Set Development Disease EP300 gene Electroencephalography Emotional Emotions Environment Environmental Exposure Epidemiologic Studies Epidemiology Equation Evaluation Family Functional disorder Funding Future Galvanic Skin Response Glycyrrhetinic Acid Goals Heart Rate Impaired cognition Impairment Individual Interdisciplinary Study International K-Series Research Career Programs Knowledge Lead Letters Life Cycle Stages Literature Location Long-Term Effects Longitudinal Studies Measurement Measures Mediating Mediation Mediator of activation protein Metals Modeling National Institute of Environmental Health Sciences Neurobiology Neurocognitive Neurocognitive Deficit Neurologic Neurosciences Nursery Schools Outcome P300 Event-Related Potentials Parenting behavior Pathogenesis Pathway interactions Pennsylvania Performance Personal Satisfaction Prevention strategy Principal Investigator Problem behavior Process Psychophysiology Public Health Quality of life Records Research Research Personnel Resources Risk Risk Factors Sampling Schools Shapes Social Environment Staging Stress Symptoms Testing Time Toxic Environmental Substances Toxic effect Toxicology Universities Update Violence Work base behavior measurement blood lead boys cohort early adolescence experience externalizing behavior follow-up girls global health improved innovation lead exposure neurobehavioral neurobiological mechanism neurotoxic population based preadolescence prospective psychosocial public health relevance theories tool

项目摘要

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.

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、注意力缺陷多动症和对立障碍）已被确定为青少年犯罪和后来成人暴力的危险因素。有初步证据表明，即使处于亚临床铅暴露水平，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。根据我们在纵向队列研究中的初步分析的证据，我们建议研究学龄前时期接触铅导致青春期早期外化行为的中介机制。据推测，铅暴露会引起两种相关症状，即认知障碍（智商低、P300事件相关电位降低、学习成绩差）和情绪失调（迷走神经张力低、觉醒度低和压力反应性低），这反过来又形成了儿童外化行为的机械途径。这个新的 R01 建立在 PI 目前由 NIEHS 资助的 K 奖和来自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，他们于 2004 年获得了血铅水平，并在 6 岁时评估了他们的智商测试分数和行为测量。我们建议除了重复测量血铅、智商、行为、学校表现和青春期前的心理社会风险因素之外，还添加新的神经认知和情绪测量（估计 N = 1,200）。结构方程模型将用于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。这个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，这项研究可能为降低当前 CDC 定义的安全铅水平提供策略，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，从而改善他们一生中的福祉。公共卫生相关性：了解铅暴露对儿童外化行为的神经生物学基础，对于未来解决铅暴露和儿童外化行为这两个重要的全球公共卫生问题具有重要意义，最终有助于改善个人和家庭的生活质量单元。