Effects of the neural and inflammatory response to stress on cerebrovascular risk in HIV infection

点击翻译按钮获取中文摘要

PROJECT SUMMARY This is an application for a K23 award for Dr. Felicia Chow, who is establishing herself as an investigator in patient-oriented clinical research at the intersection of HIV and cerebrovascular disease. This K23 award will provide Dr. Chow with the support necessary to develop new research skills and attain practical and conceptual expertise in 4 key areas: 1) brain and vascular FDG-PET imaging, 2) mechanisms and measurement of psychological stress, 3) advanced statistical techniques for observational data, and 4) design, conduct and analysis of clinical trials. Dr. Chow has assembled an interdisciplinary team of mentors (Dr. Priscilla Hsue, an expert in the role of inflammation and endothelial dysfunction in the pathogenesis of cardiovascular disease in HIV; Dr. Gil Rabinovici, an expert in use of multimodal brain imaging, including novel brain PET techniques, to improve diagnosis of dementia; Dr. Elissa Epel, an expert on measurement of stress and its effects on inflammation and cardiometabolic disease; Dr. Frederick Hecht, an expert on stress and mindfulness-based interventions in HIV; Dr. Peter Bacchetti, an expert on statistical approaches to analyzing observational HIV data), who will guide her research and career development. This multi-layered mentorship structure, embedded in a highly collaborative training environment, will be critical to her development into an independent investigator, with the ultimate goal of optimizing cerebrovascular health in people living with HIV. With the evolution of HIV infection into a chronic, treatable disease, people with HIV face excess risk of several non-AIDS-related complications, including stroke. Traditional vascular risk factors (e.g., hypertension, smoking) account for only a portion of excess cerebrovascular risk in HIV. This proposal will investigate the role of psychological stress, which is highly prevalent in people with HIV, in HIV-associated cerebrovascular risk. Dr. Chow hypothesizes that psychological stress activates pro-inflammatory pathways that contribute to elevated cerebrovascular risk in HIV. She will leverage the research infrastructure of two NIH-funded studies to evaluate the association of stress with the neural inflammatory pathway (i.e., amygdala activity, immune activation, inflammatory cytokines) in Aim 1 and with cerebrovascular risk markers (i.e., carotid arterial inflammation on FDG-PET and cerebral vasoreactivity by transcranial Doppler ultrasound) in Aim 2 in a cross-section of people with well-controlled HIV. In Aim 3, she will pilot a controlled trial of a mindfulness-based stress reduction intervention in a subset of high-stress individuals with HIV to gain preliminary insight into the impact of mindfulness on the neural inflammatory pathway and on cerebrovascular risk markers. This proposal is a crucial step toward uncovering the contribution of psychological stress to cerebrovascular risk in people with HIV and developing a larger randomized controlled trial to rigorously test the effectiveness of a stress reduction intervention as an adjunctive strategy to improving cerebrovascular health in people with HIV, which will be the focus of an R01 application to be prepared and submitted before the end of the award period.