Chronic social stress during childhood produces adverse outcomes on neurodevelopment and in turn deficits in socioemotional, motivational and cognitive functions. Currently, the effects of stress and resulting neurodevelopmental alterations (specifically, prefrontal cortex structural and functional connectivity with both amygdala and striatum) that impact emotional and impulse control and reward in children are poorly understood. The objective of the proposed research is to elucidate the mechanisms by which chronic social stress contributes to the over-consumption of a calorically dense diet (CDD) and how both stress and the resulting obese phenotype affect neurodevelopment in females using a rhesus monkey model. In addition, potential biological signals linking the adverse social experience and increased fat mass to neurobehavioral deficits will be examined. For this, I will investigate whether chronic postnatal exposure to a social stressor (social subordination in rhesus macaques), developmentally contributes to overconsumption of a CDD and whether the resulting obesity has a synergistic effect, further altering the developmental trajectory of brain and behavior. Female monkeys, who will be cross fostered at birth to control for the potential confounding effects of heritable factors and maternal stress during gestation, will be studied longitudinally from birth through pre-puberty (16 mo) as detailed in the aims below.
In Aim 1, I will examine whether chronic social stress impairs the development of emotional and stress regulation as well as inhibitory control of behavior, leading to the emergence of emotional feeding. Emotional reactivity and impulsivity will be examined longitudinally using well-established testing paradigms.
Aim 2 will examine the neurobiological underpinnings of the behavioral alterations studied in Aim 1, focusing on chronic stress-induced impairments of the developmental trajectory of prefrontal cortex (PFC) connectivity with amygdala (AMYG) and ventral striatum (nucleus accumbens: NAcc). For this, I will employ state-of-the-art longitudinal neuroimaging approaches involving Diffusion Tensor Imaging (DTI) and resting state functional connectivity Magnetic Resonance Imaging (rs-fMRI) to assess the effects of social stress on the development of structural and functional connectivity of these circuits. Finally, for Aim 3 I will test the hypothesis that stress- induced consumption of a CDD will lead to the emergence of obesity that will further impair PFC-AMYG and PFC-NAcc structural and functional connectivity and resulting behavior. This research provides an invaluable opportunity for training in behavioral neuroscience that will allow me to investigate how stress, emotional feeding, and resulting obesity adversely affect neurobehavioral development in a translational animal model for girls.
Chronic exposure to stress and obesity during childhood have each been found to produce persistent adverse effects on health, such as altered brain structure and function, behavioral problems, and mood and anxiety disorders. However, it is unclear whether stress and obesity act independently of one another, or alternatively, whether stress interacts synergistically with obesity to worsen these adverse outcomes. This project will determine how social stress and increased fat mass affect neurobehavioral development in a controlled experimental setting using an animal model that exhibits high translational validity with the neurobehavioral health of human children.
