Identifying how individual differences in risk for disease emerge is a major target for biomedical research. Early life experiences may be pivotal in lifetime risk of disease and other adverse outcomes. The public health significance of identifying the scope, extent, and mechanisms by which early experiences alter health trajectories across the lifespan is extraordinarily high. Early childhood represents a critically valuable window for prevention and intervention aimed at averting costs, both in terms of human suffering and economic burden, that otherwise have the potential to escalate across an individual's life. Adversity in childhood is a potent risk factor for a range of negative health outcomes persisting throughout the lifespan. Uncovering how these early experiences generate increased risk and variation in health trajectories is important for the development of better prevention, intervention, and treatment strategies to improve human health. Animal models and animal research are essential to achieving these goals. Nonhuman primate studies offer significant and unique opportunities for understanding the consequences of early adverse experiences on complex biobehavioral, cognitive, and neurobiological functions across a relatively long lifespan that parallels humans in terms of maturational processes. Longitudinal research that addresses the lifelong consequences of early life events in monkeys is exceptionally sparse, however. The dearth of information about how early adverse experiences alter development and health across the middle- and later-life periods poses a challenge to use of this animal model for research. The broad goal of the research proposed here is to address these critical gaps in knowledge. The studies will use a longitudinal research approach to identify the consequences of different early rearing experiences (nursery- versus mother-reared) on specific aspects of behavior and brain in middle- age (14-19 years;approximate range within 40-60 human years) in an existing population of adult rhesus monkeys.
The specific aims of this research are: 1) To determine the long-term effects of early differential rearing on specific aspects of behavior in rhesus macaques;2) To determine the long-term effects of early differential rearing on both global and specific aspects of brain morphology and cerebral composition using magnetic resonance imaging (MRI);3) To assess the relationship between performance on cognitive, learning and memory tests and structural aspects of the brain in these nursery- and mother-reared monkeys;and, 4) To evaluate age-related changes in both brain and behavior across the middle-age maturational period. These studies will leverage a unique existing population of animals to produce new and immediately useful data on cognition, learning, memory, and brain in the middle-age maturational period. Together, the proposed studies will address unanswered questions about a long-standing animal model of childhood adversity and will produce novel information about the consequences of early experience on health across the lifespan.

Public Health Relevance

Childhood impoverishment, stress, and adversity are part of a risk pathway for a broad range of deleterious health outcomes across the lifespan. Understanding how early experiences alter the trajectory of healthy development is critically important to research on human health. The proposed studies will provide important information about the long-term consequences of early stress on brain and cognitive behavior in adult monkeys and, in turn, will shed light on how early experience alters health trajectories across the lifespan and how we might develop better treatment, prevention, and intervention strategies to promote human health.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MESH-L (02))
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Zehr, Julia L
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Wake Forest University Health Sciences
Schools of Medicine
United States
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