February 13, 2009
Identification and Characterization of Sensitive Periods for Neurodevelopment of Mental Illness
NAMHC Concept Clearance
Julia L. Zehr, Ph. D.
Chief, Trajectories of Behavioral Dsyregulation Program
Chief, Integrative Studies of Biology and Behavior Program
Developmental Trajectories of Mental Disorders Branch
Division of Developmental Translational Research (DDTR)
This initiative will stimulate neurodevelopmental research in humans and animals that will increase our understanding of the neurobiology underlying developmentally sensitive periods for risk, resilience, and intervention.
Rationale and Description
The goal of this initiative is to accelerate and stimulate research on sensitive periods (i.e., periods during which the developing brain is maximally sensitive to environmental influences that confer risk or resilience) for the neurodevelopment of mental illness. While brain development may start from a genetic blueprint, it is the overlay of experience that shapes development and leads to either normal function or pyschopathology. We have limited knowledge of either the timing and specificity of sensitive periods in humans or the neurobiological trajectories in mental disorders. By increasing research focused on sensitive periods in behaviors related to mental health, the field will make exponential progress in the treatment of mental illness. Furthermore, with more fundamental information on sensitive periods in humans, we can develop more specific and focused hypotheses about mechanisms to be tested in preclinical animal models. Therefore, the potential advances gained from this initiative are essential for the ultimate understanding, prevention, and cure of mental disorders.
This initiative would support investigations of sensitive periods in the development of cognitive or affective function and behaviors relevant to mental health disorders. In particular, applications may address sensitive periods in the development of normal function or psychopathology, sensitive periods for intervention to prevent, pre-empt, and/or treat mental illness, and the mechanisms underlying the interaction between genetics, experience, and development.
Examples of possible studies:
- Identify sensitive periods for developmental perturbations in the etiology of psychopathology, including bipolar disorder, schizophrenia, and depression.
- Test the impact of pharmacological or behavioral interventions during different stages of development.
- Use knowledge of brain maturation to develop novel, targeted interventions for psychopathology with age-specificity.
- Determine the neurobiological mechanisms that give rise to sensitive periods and explore how they can be manipulated to modify a sensitive period and confer risk or resilience.
- Assess the effects of early risk factors (e.g., immune, maternal stress, drugs) on gene expression, synapse formation or morphology, physiology, and behavior across development.
- Evaluate developmental changes in epigenetic coding of experience, including developmentally regulated actions of non-coding RNAs, siRNAs, and anti-sense RNAs.
- Use genetically tractable animal models to evaluate the interactions between genetics, environment, and development.