Early life exposure to metal mixtures and neuroimaging of internalizing behaviors in childhood

生命早期接触金属混合物和童年内化行为的神经影像

基本信息

批准号：
10018518
负责人：
Megan K Horton
金额：
$ 60.12万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018518
关键词：
11 year old 7 year old Adolescent Adult Adverse effects Affect Age Amygdaloid structure Anatomy Anterior Anxiety Area Assessment tool Behavior Behavioral Biological Markers Birth Brain Brain region Categories Child Child Support Childhood Cognition Cognitive Cohort Studies Data Development Developmental Process Diffusion Magnetic Resonance Imaging Disease Dose Elderly Elements Emotional Environmental Epidemiology Environmental Exposure Environmental Health Environmental Risk Factor Exposure to Face Functional Magnetic Resonance Imaging Funding Future High Prevalence Hippocampus (Brain)Incidence Individual Infant Intervention Lateral Lead Life Life Cycle Stages Link Long-Term Effects Magnetic Resonance Imaging Manganese Maps Measures Medial Mediating Mediation Mental Depression Mental Health Mental disorders Metal exposure Metals Mexican Mexico Minor Modeling Motion Neurotoxins Nutrient Outcome Perinatal Phenotype Population Predisposition Prefrontal Cortex Pregnancy Prevalence Procedures Property Psychopathology Public Health Reporting Research Rest Risk Risk Factors Role Sampling Shapes Statistical Methods Statistical Models Structure Substance abuse problem Symptoms Testing Time Tooth structure United States Zinc affective neuroscience behavior test behavioral phenotyping childhood anxiety cingulate cortex cognitive function cohort cost effective deciduous tooth depressive symptoms design disability early awareness early childhood early life exposure environmental chemical fetal follow-up improved innovation lead exposure model design multimodality neural circuit neural network neurobehavioral neurodevelopment neuroimaging neurotoxic neurotoxicity novel phenotypic data prenatal influence prospective public health intervention relating to nervous system suicidal behavior toxicant

项目摘要

PROJECT SUMMARY Pediatric internalizing disorders, including anxiety and depression, lead to considerable public health burden. Our understanding of internalizing disorders has lagged behind advances in our understanding of other pediatric psychopathologies. The neural circuitry underlying internalizing behaviors, including the prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate cortex, amygdala and hippocampus develop early during developmental processes. Unlike adult neural networks, which are relatively stable, infant and child neural networks are dynamic, and need to be considered as vulnerable developmental trajectories. Even minor environmental disruptions early in life can set in motion deviations from normative trajectories that are not clinically evident for years. Environmental chemicals, such as metals, can exert neurotoxic effects during these critical windows of vulnerability. Advances in neuroimaging (i.e., magnetic resonance imaging; MRI) allow us to non-invasively test the influence of the environmental exposures on the neural circuitry in children. The influence of prenatal and early childhood metal exposure on these internalizing symptoms and the underlying neural circuitry has not yet been examined, even though early exposures to metals has been shown to adversely affect cognitive domains supported by the same circuitry. In the proposed study, we will leverage an ongoing prospective birth cohort study focused on examining associations between early life metal exposure and child cognition. We will introduce new follow-up measures including MRI and behavioral testing to assess internalizing symptoms in a sample of 300 variably exposed children at age 10-11 years. Using an innovative tooth biomarker that reconstructs integrated measures of metal exposure throughout gestation and early childhood, we focus on 3 neuroactive metals including: lead (Pb), a known toxicant; manganese (Mn) an essential nutrient with growing recognition as a neurotoxicant; and zinc (Zn) an essential nutrient with potential to mediate adverse effects of neurotoxicants. Using data-driven statistical models designed to leverage the temporality of the tooth data, we propose to identify and define critical developmental windows of susceptibility to individual metals and to the metal mixture. In addition, exploratory analyses will examine the link between MRI findings and behavioral phenotypes to further understand the mechanisms of metal neurotoxicity. This study bridges the fields of affective neuroscience and neuroimaging with environmental epidemiology. Few environmental health studies have brought together these three fields within a large cohort designed to test risk factors of child neurodevelopment; thus our study will help shape our overall understanding of the long-term effects of early life metal exposure and set the stage for developing effective public health interventions that can improve emotional, behavioral and cognitive functioning in children.

项目概要儿童内化障碍，包括焦虑和抑郁，导致相当大的公共健康负担。我们对内化障碍的理解落后于我们对其他疾病的理解的进步儿科精神病理学。内化行为背后的神经回路，包括前额叶皮层、外侧眶额皮层、前扣带皮层、杏仁核和海马体在早期发育发展过程。与相对稳定的成人神经网络不同，婴儿和儿童神经网络网络是动态的，需要被视为脆弱的发展轨迹。甚至轻微生命早期的环境破坏可能会导致与规范轨迹的偏离，而这些轨迹并不是多年来临床表现明显。环境化学物质，例如金属，可以在这些过程中产生神经毒性作用脆弱性的关键窗口。神经影像学（即磁共振成像；MRI）的进步使我们能够非侵入性测试环境暴露对儿童神经回路的影响。这产前和儿童早期接触金属对这些内化症状及其潜在的影响尽管早期接触金属已被证明可以改善神经回路，但尚未对神经回路进行检查。对同一电路支持的认知领域产生不利影响。在拟议的研究中，我们将利用正在进行的前瞻性出生队列研究的重点是检查生命早期金属暴露之间的关联和孩子的认知。我们将推出新的后续措施，包括 MRI 和行为测试来评估对 300 名 10-11 岁不同暴露儿童的样本进行内化症状。使用创新的牙齿生物标记物，可重建整个妊娠期和早期金属暴露的综合测量值童年时，我们关注 3 种神经活性金属，包括：铅 (Pb)，一种已知的有毒物质；锰 (Mn) 和日益被认为是一种神经毒物的必需营养素；锌 (Zn) 是一种具有潜力的必需营养素介导神经毒物的不良反应。使用旨在利用数据驱动的统计模型由于牙齿数据的暂时性，我们建议识别和定义易感性的关键发育窗口单个金属和金属混合物。此外，探索性分析将检查之间的联系 MRI 结果和行为表型可进一步了解金属神经毒性的机制。这研究将情感神经科学和神经影像学领域与环境流行病学联系起来。很少环境健康研究将这三个领域汇集到一个旨在测试风险的大型队列中儿童神经发育因素；因此，我们的研究将有助于形成我们对长期的整体理解生命早期接触金属的影响，并为制定有效的公共卫生干预措施奠定基础可以改善儿童的情绪、行为和认知功能。