Psychosocial stress, cardio-respiratory fitness, and the medial temporal hippocampal system in Black emerging adults

Boston University Medical Campus, Boston MA

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Abstract

SUMMARY/ABSTRACT The goal of this proposed research is to examine how cardiorespiratory fitness and chronic psychosocial stress modulate the medial temporal hippocampal system in Black emerging adults aged 18 to 25 years. Emerging adulthood is a life period of self-exploration that is experienced by the majority of emerging adults as stressful. Chronic stress and cardiorespiratory fitness (henceforth, fitness) are well-known, opposite modulators of the medial temporal hippocampal system (henceforth, hippocampal system), but the neurobiological basis of this modulation in humans is unknown. Theoretical and animal models point to a shared neurobiological basis for exercise- and stress-induced modulation of the hippocampal system: up- vs. downregulation, respectively, of hippocampal plasticity mechanisms. These models highlight expression of brain derived neurotrophic factor and an important role for adult-born, immature neurons in the dentate gyrus subfield of the hippocampus in a computational process known as pattern separation that is critical for memory formation and implicated in anxiety and depression. Whether allostatic load, the physiological ‘wear and tear’ response to chronic stress across multiple biological systems is associated with hippocampal system function is unclear, but critical for understanding this system’s role in mental and brain health. In contrast, greater fitness correlates with better mental health and hippocampal system function and structure in young adults. Despite this knowledge we do not know how putative markers of brain plasticity and allostatic load interact to modulate the hippocampal system in emerging adults. Here, we propose to examine this brain system’s plasticity by combining a fitness test and a blood serum test to measure brain derived neurotrophic factor with a psychosocial stress interview, hippocampal subfield-level circuit assessments using high-resolution functional and structural magnetic resonance imaging, and mnemonic discrimination tasks designed to tax pattern separation. Our central hypothesis is that chronic stress will negatively correlate with hippocampal system function and positively with allostatic load, whereas fitness will positively correlate with hippocampal system function and serum brain derived neurotrophic factor and negatively with allostatic load. We will examine this hypothesis with three Specific Aims. Aim 1 will examine impact of fitness on the hippocampal system, serum brain derived neurotrophic factor, and allostatic load, and Aim 2 will examine the impact of chronic psychosocial stress on the hippocampal system and allostatic load. Aim 3 is exploratory and will examine the impact of cumulative chronic psychosocial stress and fitness on the hippocampal system mechanistically via allostatic load, serum brain derived neurotrophic factor and mental health using structural equation modeling. A positive outcome of this research will provide evidence for an interplay between allostatic load and neuroplasticity mechanisms as opposing mechanisms affecting the hippocampal system and will fill an important knowledge gap about chronic psychosocial stress as a negative modulator of brain health and hippocampal plasticity in Black emerging adults.