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Strategic Objective 2

Strategic Objective 2 focuses on the crucial component of development, elucidating how brain and behavior change across the lifespan in health and illness.

Strategic Objective 2: Chart Mental Illness Trajectories To Determine When, Where, and How to Intervene

In the past, we viewed mental illnesses as chronic conditions defined by their symptoms. However, based on our understanding of brain disorders, it seems likely that manifest mental illnesses are the late signs of changes in brain circuits and subtle disruptions in behavior and cognition that begin years earlier. These early abnormalities may influence the course of subsequent brain and behavioral development and establish a trajectory of mental illness.

Development is not a uniform, linear process. Rates of developmental change vary considerably across brain regions. For example, the regions of the adolescent brain involved in emotional responses are fully active, or even more active than in adults, while those areas involved in keeping emotional, impulsive responses in check are still reaching maturity. Moreover, the brain does not reach full maturity until well past 20 years of age. The dynamic nature of development and the observation that most mental illnesses emerge during the first two decades of life prompt critical questions: What are the earliest markers or signs that distinguish typical from atypical brain development? How do these markers or signs differ in meaningful ways across individuals and diverse populations (e.g., by sex, gender, age, race, ethnicity) and varied environmental (e.g., cultural, economic, geographical, social, technological) or experiential exposures? How can we intervene early to prevent the development of mental illnesses?

With the advent of more powerful and precise imaging technology and analysis methods, scientists have the tools to track brain and behavioral development. Concomitantly, our ability to understand the complexities of these processes in association with mental illnesses is growing. For example, studies have demonstrated that the genes and proteins expressed in the fetal and postnatal brain are so radically different that one could consider the fetal and postnatal brains as different organs with different functions.21,22 Furthermore, increasing evidence has linked the trajectory of brain development with the emergence of symptoms of mental illness in early life, such as psychosis in late adolescence or autism in very early childhood.

Developing a comprehensive picture of typical and atypical brain and behavioral development across the lifespan (conception to late life) and in diverse populations will help tell us when, where, and how to intervene. A focus on the early, presymptomatic phase of a mental illness is critical, as this may provide the best opportunity to identify individuals at highest risk and intervene at the earliest possible time. It will also be essential to identify and characterize sensitive periods across the full lifespan—that is, identify discrete time periods during which the impact of experience is particularly strong. Progress here will allow us to know the points in time during which the brain is most sensitive to intervention and the underlying molecular-, cellular-, and system-level mechanisms responsible for this sensitivity. For the person with or at risk for a mental illness, findings from this research could lead to earlier diagnosis, earlier and more effective preventive and therapeutic interventions, and, ultimately, an improved outcome.

Our ability to prevent and treat mental illnesses and gauge the effectiveness of interventions depends on the identification of valid biomarkers and behavioral indicators; these tell us who is at risk, when development is going awry, or when an intervention is restoring function. To do this, we must increase our knowledge of the mechanisms through which multiple and interacting risk and protective factors operate. Knowledge of these risk and protective factors will provide the basis on which to develop novel clinical tools and effective interventions.

To better understand the progression of mental illnesses and lay the foundation for predicting outcomes and preemptive interventions, NIMH will employ the following strategies:

Investigating the interdependence and functional development of simultaneously maturing—yet unevenly progressing—systems and competencies will break new ground in understanding the development of mental illnesses. To understand what factors influence development and the risk for mental illnesses across diverse populations, we must create a comprehensive, cross-lifespan map of trajectories (i.e., growth curves) of typical and atypical brain, cognitive, and behavioral development. Basic and translational research studies that describe the behavioral maturation and associated molecular-, cellular-, and circuit-level changes that occur over a lifespan are needed to create this map. To implement this strategy, NIMH will support research to:

  • Characterize developmental processes across biological and behavioral domains of analysis that give rise to mental illnesses throughout the lifespan.
  • Identify sensitive periods for typical and atypical mental health trajectories.
  • Determine modifiers of maturational and illness trajectories, emphasizing periods of sensitivity to perturbation and/or potential for intervention.

The best time to address a mental illness is before the appearance of symptoms that disrupt daily life. Preemptive interventions will rely on biomarkers that give health care providers the ability to predict the onset of illness for individuals, not just populations, at risk. To realize this, research must identify biomarkers and behavioral indicators with high predictive value, as early in the course of illness development as possible. Imagine a world where a straightforward set of physiological and/or cognitive tests indicates with high sensitivity and specificity an individual’s risk for developing a mental illness, and points to an effective tailored intervention. To ensure this future, we must work today to identify markers of illness progression at molecular, cellular, circuit, and behavioral levels. To implement this strategy, NIMH will support research to:

  • Identify early biological and environmental risk and protective factors and their underlying mechanisms to serve as novel intervention targets.
  • Develop biomarkers and assessment tools to predict illness onset, course, and intervention response across diverse populations.