Identifying Unique Neural and Inflammatory Mechanisms of Depression in People Living with HIV

ABSTRACT People living with HIV (PLWH) are particularly vulnerable to depression, which negatively affects their quality of life, medication adherence, and even mortality. Nearly 60% of PLWH suffer from depression, yet little is known about the underlying mechanisms of depression in HIV. Understanding how HIV-associated chronic inflammation interacts with neural mechanisms to contribute to depression is critical in guiding future treatment efforts. We will test a model of depression in PLWH in which inflammation contributes to a distinctive pattern of brain network dysfunction. In a cross-sectional study, we will enroll PLWH who are depressed (n=80) and non- depressed (n=60), and HIV- subjects who are depressed (n=80) and non-depressed (n=60). We will address several significant knowledge gaps by Human Connectome Project protocols to implement resting-state fMRI to measure functional connectivity and task-based fMRI to probe Negative Valence Domain and emotion regulation networks. We will also measure peripheral inflammatory markers and NF-κB (an upstream regulator of expression of pro-inflammatory cytokines) to assess inflammation. Measures of tryptophan catabolism will also be considered as mediators of the effects of inflammation on depression. These data will elucidate how HIV status, inflammation, and depression interact with critical brain networks to identify potential biomarkers and treatment targets.