Project Summary/Abstract Depression is the second leading cause of disability worldwide and frequently co-occurs in patients with chronic diseases. Individuals with depression and comorbid chronic disease experience poorer disease outcomes and increased risk for mortality, compared to those without depression. Up to 38% of people with hypertension—the most common diagnosis in ambulatory care practices— have comorbid depressive disorders, and depression is independently associated with poor blood pressure control and an up to 14-fold increase in mortality in these patients. Although depression is common and eminently treatable, 50% of patients with depression remain undiagnosed or inadequately treated in primary care settings. The primary focus of this project is to investigate highly promising evidence that a telephone-delivered mindfulness intervention (UPLIFT; Using Practice and Learning to Increase Favorable Thoughts), which reduces depression in patients with epilepsy, may be effective for reducing depressive symptoms in hypertension patients. UPLIFT has cost, accessibility, and scalability advantages over other psychological treatments for depression because it does not require licensed clinicians for delivery and is delivered by phone in a group-based format. The proposed research will: 1) adapt and establish the feasibility and acceptability of UPLIFT in patients with hypertension; 2) establish effect size estimates of UPLIFT vs. usual care in a pilot randomized controlled trial; and 3) explore and test promising mediators and moderators of the effects of UPLIFT. The research project goals focus not only on addressing the need for widely accessible and evidence-based depression treatments in primary care settings, but have been developed to impart key competencies to the candidate whose long-term career goal is to establish an evidence base for affordable, accessible, and scalable mind-body interventions for patients with the often debilitating combination of depression and chronic disease. Targeted areas of research training include: 1) practice-based clinical trials; 2) psychobiological assessments (i.e., actigraphy and ecological momentary assessment); 3) advanced research design and analysis; and 4) protection of human subjects. Support for the proposed project and training goals will be provided by the exceptional resources available at the NYU Langone Medical Center and by the expertise of the candidate’s mentoring team comprised of nationally recognized and NIH-funded behavioral (Drs. Ogedegbe and Spruill) and sleep (Dr. Jean-Louis) scientists. Consultants on the project will provide additional expertise in the areas of mixed methods research and biostatistics.