Using a primate model, we build on our previous research to test the novel hypothesis that exposure to moderate levels of maternal rejection early in life "inoculates" the developing infant by permanently altering cognitive appraisal of, and neuroendocrine sensitivity to, subsequent stressors (i.e., stress resilience). In contrast, we posit that exposure to too little or too much rejection-related stress leads to stress vulnerability later in life. We also test the hypotheses that these maternal influences on the development of stress resilience and vulnerability 1) result from long-term alterations in the activity of the serotonergic system, the HPA axis, and other stress-sensitive neurobiological systems, and 2) are modulated by risk or protective factors such as polymorphisms in the serotonin transporter (SERT) gene and amount of social support. This 5-year project will be conducted with the free-ranging population of rhesus macaques on Cayo Santiago, PR. Two cohorts of 45 infants (n=90) will be followed longitudinally from birth through 3 years of age. Infants will be classified on the basis of the amount of maternal rejection they receive (low, moderate, high) in the first 2-3 months of life. All infants will be SERT genotyped and homozygous or heterozygous individuals for the long and the short allele (l/l, l/s, and s/s) will be identified. Data on dominance rank, maternal protectiveness, and social support (social network size;grooming received;aid during agonistic interactions) will be quantified. Stress vulnerability and resilience will be operationalized with behavioral and neuroendocrine measures. Behavioral measures will include: a) independence from the mother;b) social competence during interactions with conspecifics;and c) behavioral inhibition and anxiety in response to "challenge" tests involving exposure to novel objects, unfamiliar humans, and risky social situations. Detailed characterization of HPA axis physiology and other stress-related neurobiological systems will be obtained through: a) frequent fecal sample collection to determine basal and stress-induced cortisol levels;b) assessment of plasma concentrations of ACTH and cortisol in response to psychosocial stress (social separations) and pharmacological challenges (CRF challenge, dexamethasone suppression test, metyrapone test, ACTH challenge);and c) assessment of stress-induced CSF concentrations of CRF, oxytocin, and monoamine metabolites. By conducting experimental research with free-ranging primates we maximize the ecological validity of our findings. This research will provide original information on the neuroendocrine mechanisms through which exposure to variable parenting can affect the development of stress vulnerability and resilience in children, and how genetic and environmental factors may influence these development outcomes. This research will also enhance our understanding of normative interindividual variation in the development of emotion regulation and stress-related disorders. Ultimately, this research may provide important information on the efficacy and potential limitations of parenting interventions designed to foster resilience in children based on controlled exposure to, and mastery of, psychosocial adversity.

Public Health Relevance

The proposed project will provide original information on the neuroendocrine mechanisms through which exposure to variable parenting can affect the development of stress vulnerability and resilience in children. It will also enhance our understanding of how parental influences on the development of stress reactivity are modulated by genetic and environmental factors. Findings of this research have important implications for understanding normative interindividual variation in the development of emotion regulation as well as stress-related disorders in children.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01HD067175-04
Application #
8686907
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Freund, Lisa S
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Chicago
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60637
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