Description (from grant):
This project proposes to investigate systemic inflammation, blood-brain-barrier (BBB) permeability, and reward functions in the study of comorbid depression in people with HIV (PWH). Depression is the most common neuropsychiatric illness among PWH, with an average prevalence of up to 78% in some cohorts. Alarmingly, it is estimated that by 2030, the top two leading causes of disease burden globally will be HIV and depressive disorders. These data highlight the urgent need for research focusing on neurobiological mechanisms underlying HIV/depression comorbidity. Our proposal addresses this need. Our proposed model: (1) HIV infection induces systemic inflammation [peripheral blood mononuclear cells (PBMC), cytokines]; (2) systemic inflammation extends to the CNS through transmigration of PBMC subtypes through the BBB; (3) disruption of BBB integrity and neuroinflammation lead to alterations in the reward circuitry, contributing to depression in PWH. We will test the overall hypothesis that PWH exhibit increased systemic inflammation and BBB disruption, leading to reward dysfunction and depression. We will utilize a 2×2 factorial design: 1) 100 depressed PWH; 2) 100 non-depressed PWH; 3) 50 depressed HIV negative people; and 4) 50 HC. We will include subthreshold depression to capture a wide range of depression severity. Study procedures will assess psychopathology, reward, anxiety, trauma, cognition, HIV treatment, CD4+ count, viral load (VL), and immune assays.