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

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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.