Background

Longitudinal studies of early childhood development have contributed to substantial evidence regarding the impact of socioenvironmental factors, defined as variables in one’s social and physical environment that interact with brain and cognitive function. Prospective longitudinal studies such as the Adolescent Brain and Cognitive Development (ABCD) study are integrating approaches informed by public health, developmental cognitive psychology, and neuroscience to examine socioenvironmental factors impacting neurocognitive development and the emergence of risk phenotypes for substance use disorders (SUD) and their comorbidities. Importantly, these and similar studies are providing data needed for the application of computational approaches to build and test predictive and explanatory models of relationships between early life socioenvironmental factors and the maturation of neurocognitive and social behavioural processes relevant to SUD.

However, complementary studies designed a priori to test hypotheses generated by these cohort studies are needed to fully elucidate brain developmental mechanisms linking early social environment to SUD risk. Studies in non-human species are necessary for revealing fundamental, conserved neurobiological and neurobehavioral processes underlying cognitive function. Moreover, as we have an increasing array of tools that allow for a priori control of neural and environmental variables that cannot be experimentally manipulated in humans, translational research in non-human species (i.e., “animal models”) can be a powerful means of testing hypotheses generated from research in humans. There have been major advances in tools for high-resolution tracking of neural development, as well as cell- and circuit-specific imaging, recording and manipulation in multiple species, including rodents and primates, and the pace of innovation is increasing. In parallel, the computational tools needed for harnessing dense, multidimensional data sets have also advanced.

Together, these tools have dramatically increased our potential for discovery and deeper understanding of fundamental neurodevelopmental and neurobehavioral processes. Of relevance to the broad question of developmental factors and processes that influence risk for, or resilience to, SUD, there is a rich body of research in non-human species examining neurobiological processes and socioenvironmental factors in the development and maturation of cognitive and behavioural function. A large body of research also uses rodent and non-human primate species as models to examine neurocognitive mechanisms relevant to SUD. Yet there are relatively few studies designed to examine the neurocognitive developmental mechanisms and trajectories that may link early life socioenvironmental factors to vulnerability for, or resilience against, SUD in adolescence and adulthood, and very few of those apply advanced tools for molecular, cellular and circuit monitoring and manipulation.

Moreover, while computational modelling has proven to be a powerful approach for revealing relationships between early-life social factors and SUD risk in humans, there is currently no resource that can be leveraged to build cross-informative computational models from animal model data to reveal potential causal relationships across early socioenvironmental manipulations, neurobehavioral developmental trajectories, and the emergence of SUD-relevant neurocognitive phenotypes. Translating Socioenvironmental Influences on Neurocognitive Development and Addiction Risk (TranSINDA) was developed to address these gaps by supporting a set of coordinated research projects in animal models featuring the use of advanced neuroscience and developmental cognitive approaches and research designs that will integrate.

1. Early-life manipulations designed to model socioenvironmental risk factors for SUD and their comorbidities,

2. Longitudinal assessments of neurocognitive development, and

3. Characterization of SUD risk-relevant neurocognitive function in adolescence and/or adulthood.

This research program will additionally support the coordinated generation of a data set for building computational models to elucidate meaningful relationships linking early socioenvironmental conditions, neurocognitive developmental trajectories, and the emergence of SUD risk-relevant neurobehavioral phenotypes. If successful, the TranSINDA research program and database will lead to an increased understanding of developmental windows that may be most sensitive to the effects of socioenvironmental factors and the discovery of new potential neurobehavioral targets for interventions to prevent SUD.

Purpose

The goal of this TranSINDA notice of funding opportunity (NOFO) is to support team science research projects aimed at employing longitudinal research designs in animal models and advanced neuroscience and theoretical tools to elucidate mechanisms mediating the impact of the early-life social environment on neurobehavioral development and the emergence of neurobehavioral phenotypes relevant to risk for, or resilience to, SUD and their comorbidities. The supported projects will be informed by SUD research in humans and animal models, and by theories and methods in cognitive development, developmental psychobiology, and developmental neuroscience.

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