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Priorities for Strategy 2.1

Updated: January 2019

Characterize the developmental trajectories of brain maturation and dimensions of behavior to understand the roots of mental illnesses across diverse populations

The fundamental intent of this strategy is to support research that breaks new ground in understanding the development of mental illnesses from early life through illness course to guide the development of preventive or preemptive interventions. NIMH encourages studies that seek to characterize developmental processes across biological and behavioral domains of analysis that increase risk for or give rise to mental illnesses throughout the lifespan; to identify sensitive periods for typical and atypical mental health trajectories across racial, ethnic, and socioeconomically diverse populations; and, to determine modifiers of maturational and illness trajectories, emphasizing periods of sensitivity to perturbation and/or potential for intervention. Applications should take into account the dynamic and non-linear nature of development, simultaneously evaluate multiple domains of function, and incorporate normative maturational influences.

Research Priorities:

  1. Characterize developmental processes across biological and behavioral domains of analysis that give rise to mental illnesses throughout the lifespan.

    Priority areas include:

    1. Characterizing the interdependence and functional development of simultaneously occurring yet unevenly progressing developmental trajectories in different brain regions and circuits; examining dynamic models of psychopathology that take into account these evolving competencies and neural plasticity.
    2. Examining individual differences and biologic, behavioral, and environmental (including social and cultural) contributors to heterogeneity across development, trajectories of treatment response, and outcomes.
    3. Examining the developmental trajectory of genomic (somatic variation), epigenomic, transcriptomic, metabolomic, and proteomic changes underlying pathophysiology in adequately powered central nervous system tissue samples. Studies using or based on a candidate gene approach are not a priority for NIMH.
    4. Applying induced pluripotent stem cell-based assays, derived from adequately powered patient and control cohorts using well-defined selection criteria, in order to recapitulate ‘omic to circuit-level developmental processes with predictive value for pathophysiology and utility for target identification and/or therapeutics discovery.
    5. Incorporating and integrating multiple levels of analysis (e.g., from genome-wide to behavioral) to identify and track trajectories of risk and resilience, function, and illness across the lifespan.
    6. Developing novel statistical, computational, and analytical techniques to integrate genomic, multi-modal imaging, clinical, and other data types across repeated assessments.
    7. Improving methods for secondary analysis of data. Approaches that combine data across studies are particularly welcome.

  2. Identify sensitive periods for typical and atypical mental health trajectories.

    Priority areas include:

    1. Conducting longitudinal studies that track changes in behavior with changes in brain development and other normative maturational processes, to characterize the progression from primary dysfunctions to subsequent impairment in domains of functioning.
    2. Identifying individual and environmental predictors of divergence from the typical trajectory as early in development as possible.
    3. Identifying and characterizing sensitive periods for brain, cognitive, social, and affective development that can be targeted for intervention to prevent, pre-empt, and/or effectively treat mental illnesses across the lifespan.
    4. Identifying the mechanisms underlying aberrant neurodevelopmental trajectories, including the functional consequences of sex and gender differences that have shown empirical associations to mental illnesses.
    5. Translating knowledge about sensitive periods and their underlying mechanisms to manipulate developmental trajectories of neural circuits and associated behaviors from the earliest possible time-point.
    6. Developing tools and methodologies for non-invasive manipulation of developmental trajectories and/or modification of sensitive periods to normalize development.
    7. Developing and validating fine-grained, objective, quantitative behavioral measures for use at different developmental stages, measurable in both laboratory and real-world; and integrating these behavioral measures with neurobiological measures across the lifespan.

  3. Determine modifiers of maturational and illness trajectories, emphasizing periods of sensitivity to perturbation and/or potential for intervention.

    Priority areas include:

    1. Identifying critical aspects of the exposome (experiences and the environment) and how particular exposures and temporal patterning shape neurodevelopment, behavioral development, and illness trajectory. Studies of the effects of environmental toxins are not a priority for NIMH.
    2. Studying neural plasticity induced by interventions in humans, including behavioral, cognitive, neurostimulation, biologic, and pharmacological approaches, and testing whether targeted interventions can lead to long-term changes in behavioral and/or brain measures.
    3. Examining the neural specificity and predictors of intervention effects and identifying sensitive periods to optimize interventions for long-term effects.