1/2 Assessing the Cumulative Impact of Early Life Substance and Environment Exposure on Child Neurodevelopment and Health

项目摘要/说明 宫内阿片类药物和其他物质暴露的神经发育后遗症是什么？简明的 这个问题的性质掩盖了人类神经发育的复杂和多方面的性质，而 环境影响的多样性，可以调节或调节物质可能具有的初始直接影响 在发育中的大脑上。从怀孕到10岁，我们的大脑经历了非凡的结构和功能 成长。包括髓鞘形成和突触形成在内的神经发育过程处于顶峰， 对遗传和环境相互作用的综合级联反应做出反应，因为它们成熟了神经系统 并为新出现的认知和行为技能提供基础。这种早期发展的模式 反映了对儿童直接和背景环境的适应，从而反映了宫内感染的潜在影响 必须在更广泛的家庭、心理社会、经济和身体范围内考虑物质暴露 环境。在过去的一年里，这些环境经历了前所未有的剧变，原因是 新冠肺炎大流行，影响儿童、家庭和怀孕个人，对 低收入家庭、种族和少数民族家庭--这些家庭已经受到持续的阿片类药物的影响 危机。我们的建议旨在了解这些融合体验对神经发育的影响。我们 将收集深度、多层次和重复的神经成像和行为表型数据，以及丰富的上下文 以儿童的生活经历为中心的环境暴露的衡量标准，包括社会公平和 社会经济因素。建立在大脑发育是一个综合过程的中心假设基础上 是由出生前的侮辱(阿片剂和其他物质暴露)和持续的出生后影响形成的 在社会、经济和健康不平等的背景下，我们将：1.描述‘神经典型’的可变性 发展，认识到反映个体适应的多种途径可能导致相同的结果； 2.检查子宫内物质暴露如何改变这些模式和途径；3.进行整体和 理解儿童环境多样性如何塑造和改变大脑的综合方法 模式和结果。实现这些目标需要仔细和有目的地计划的研究 不偏不倚的措施、社区合作伙伴和具有代表性的社会经济和人口- 有充分理由不信任研究和公共卫生工作者的社区。我们提案的核心是 访问原则。我们将利用创新的数据收集方法减少传统的参与门槛 和移动实验室，将研究带到代表性不足和边缘化的社区；并建立可信的 通过我们建立的社区咨询委员会和同龄人与我们的参与家庭建立联系 导航网络。因此，我们的做法旨在澄清接触物质对儿童的影响 发展，同时将发展神经科学和物质使用领域转向更公平的 研究标准，具有可概括的结果，可指导非惩罚性公共卫生政策。

PROJECT SUMMARY / DESCRIPTION What are the neurodevelopmental sequelae of in utero opiate and other substance exposure? The succinct nature of this question masks the complex and multifaceted nature of human neurodevelopment, and the diversity of environmental influences that can mediate or moderate the initial direct effects substances may have on the developing brain. From conception to age 10, our brain undergoes remarkable structural and functional growth. Neurodevelopmental processes that include myelination and synaptogenesis are at their peak, responding to integrative cascades of genetic and environmental interactions as they mature neural systems and provide the foundation for emerging cognitive and behavioral skills. The patterns of this early development reflects adaptation to the child's direct and contextual environments and, thus, the potential impact of in utero substance exposures must be considered within the broader family, psychosocial, economic, and physical environment. Over the past year, these environments have witnessed unprecedented upheaval as a result of the COVID-19 pandemic, impacting children, families, and pregnant individuals with disproportionate impact on lower-income, and racial and ethnic minority families - the very families already shaken by the ongoing opioid crisis. Our proposal aims to understand the neurodevelopmental impact of these converging experiences. We will collect deep multi-level and repeat neuroimaging and behavioral phenotype data, alongside rich contextual measures of environmental exposures centered on the child's lived experience, including social equity and socioeconomic factors. Building from a central hypothesis that brain development is an integrative process that is shaped by prenatal insults (opiate and other substance exposures) and ongoing postnatal influences against a backdrop of social,economic, and health inequalities we will: 1. Characterize the variability of `neurotypical' development, recognizing that multiple pathways reflecting individual adaption may lead to the same outcomes; 2. Examine how in utero substance exposures alter these patterns and pathways; and 3. Take a holistic and integrated approach to understanding how the diversity of a child's environment shapes and modifies brain patterns and outcomes. Achievement of these aims requires a careful and purposefully planned study with unbiased measures, community partners, and representative socioeconomic and demographic populations - communities with well-founded distrust of research and public health workers. At the heart of our proposal is the principle of access. We will reduce traditional barriers to participation using innovative data collection methods and mobile labs to bring the research to under-represented and marginalized communities; and build trusted connections with our participating families through our established community advisory boards and peer navigator networks. Our approach, therefore, aims to clarify the impact of substance exposure on child development whilst shifting the field of developmental neuroscience and substance use to a more equitable standard of research, with generalizable findings that can guide non-punitive public health policies.