Reducing Disparities in Mental and Metabolic Health among Predominantly Low-Income, Black and Hispanic Women with and without HIV - ABSTRACT In the United States, Black and Hispanic women (BHW) have the greatest risks of poverty, type 2 diabetes (T2D), and depression, the scope and intersection of which epitomize a syndemic. In the context of HIV, the economic, metabolic, and mental health risks are even greater, but they remain inadequately examined. Although depression disproportionately affects women with T2D and HIV, it is often missed when the three co-occur. Increased potential for missed care is of particular concern for BHW, who experience disproportionate comorbidity, socioeconomic risks, and mental health misdiagnosis. Elucidating the biology underlying relationships between poverty, depression, and metabolic health is a critical step toward improving clinical recognition of depression and identifying potent macro- and molecular-level targets for future research aimed at eliminating health disparities. Diagnosis-agnostic approaches suggest that depressive subtypes are differentially linked to socioeconomic disadvantage, metabolic indices, epigenetic age acceleration, and gut-brain axis (gut microbiome/neurobiological) dysregulation. Because environmental factors (e.g., nutrition, stress) impact gut microbes, the gut-brain axis may be a critical point at which poverty affects the body and a key pathway in the perpetuation of health disparities. Informed by the NIMHD Research Framework, the proposed observational cross-sectional study focuses on experiences of poverty across biological, behavioral, physical/built environment, and sociocultural domains at individual, interpersonal, and community levels to examine the influence experiences of poverty (low SES, adversity, material needs) on mental and metabolic health. Data from 2 cohorts of predominantly BHW with lower SES, with and without HIV will be utilized. In Aims 1 and 2, we will leverage data from women (N~2000) who participated in an NIMDH co-funded U01 study. In Aim 1 we will examine relationships among experiences of poverty, epigenetic aging, and mental and metabolic health, and in Aim 2 we will examine relationships among experiences of poverty, the gut microbiome, and mental and metabolic health. In exploratory Aim 3 we will use fMRI data from the NIMH-funded P30 Clinical Outcomes Cohort (N~100 women) to characterize the gut-brain axis by identifying gut microbiome correlates of depression- linked neurobiological substrates. The proposed research and training plan, carefully designed with guidance from an experienced, well-funded, and engaged team of expert mentors, will allow the candidate to build on prior expertise and fill training gaps in 1) integrating multiple -omic (epigenetic, microbiome) approaches, 2) bioinformatic approaches to analyzing the gut microbiome, and 3) utilizing neuroimaging data to examine brain- based symptoms. Closing these scientific and training gaps will augment the candidate’s strong trajectory toward independence and set the stage for a longitudinal R01 examining the epigenetic aging and microbiome effects of poverty on mental and metabolic health in HIV to identify objective, sentinel indicators to prompt timely clinical action—an urgently needed step toward eradicating health disparities and realizing health equity for BHW.
