Stress Biology and Psychosocial stressors as mechanisms for Racial Health Disparities in Neural and Clinical Impairments of Multiple Sclerosis

The current K00 fellowship proposal outlines an integrated post-doctoral training and research plan that will result in the applicant being prepared to independently conduct interdisciplinary biopsychosocial research as it relates to stress and neurological health outcomes. The K00 research plan will examine factors contributing to differential clinical outcomes in Multiple Sclerosis (MS), a debilitating neurological disease marked by demyelination and central nervous system lesions. Biological stress is associated with worse clinical outcomes of MS, and individuals experiencing heightened biological stress are at risk of increased incidence, disease severity, and mortality due to MS. To address the gap in understanding the mechanisms underlying these outcome variations, the research project will address the following aims: AIM 1: Determine whether regional differences are associated with longitudinal changes in biomarkers of stress (cortisol and glucocorticoid receptors), structural measures of brain demyelination (lesion load), and cognitive and physiological decline in participants with MS over time. AIM 2: Establish whether biological stress moderates structural, cognitive, and physiological decline in people with MS over time. AIM 3: Advance understanding of whether the third ventricle, as measured in clinical and research scans, is associated with cognitive or physiological decline in MS. The K00 training plan will solidify the candidate’s strengths with emerging skills while also attending to professional development and career advancement. The project spans biological stress-related outcomes that impact neurological health, specifically as they pertain to MS. To reach this goal, the applicant proposes training in: (TG1) Stress Biology, building on prior biobehavioral expertise to extend to novel biospecimens (e.g. hair) in the studies populations, and complementing stress biology with subjective measures of stress; (TG2) Neuroscience, especially structural (MRI) measures, which complement prior electroencephalography work; (TG3) Population Health Variability, to help uncover the biological and contextual underpinnings of differences in clinical MS outcomes; and (TG4) Multiple Sclerosis, a debilitating neurological disease that causes brain atrophy but for which the severity of cognitive and physiological clinical outcomes continues to elude the field. The applicant’s long-term goal is to become an interdisciplinary scholar who excels at both stress biology and neuroscience as well as advanced modeling of complex biopsychosocial factors. The research proposed will be instrumental in clarifying the tangible and multifactorial impact of stress-related processes on neurological health and MS.