National Institute of Mental Health 5K01MH136861-03

The role of monocyte metabolism and migration in inflammation-related reward circuit deficits and symptoms of anhedonia in people with HIV

This award supports research to investigate how monocyte metabolism and migration contribute to inflammation-related brain reward circuit deficits and symptoms of anhedonia in people with HIV, using clinical studies and innovative experimental platforms.

Description

The goal of this K01 is to determine the role of monocytes in HIV-related depressive symptoms with a focus on immunometabolic mechanisms that may fuel monocyte activation and trafficking to the brain and serve as therapeutic targets. The research will include clinical studies with innovative in vitro platforms such as a “human blood-brain barrier (BBB)-on-a-chip” and immune cell metabolic assessments in people with HIV (PWH) treated with baricitinib. Despite antiretroviral therapy, persistent HIV-associated inflammation impairs reward circuits and perpetuates motivational deficits like anhedonia and apathy. Activation and transmigration of circulating monocytes across the BBB are key drivers of inflammation. The study will examine monocyte glycolysis and BBB transmigration as pathways to inflammation, reward circuit deficits, and anhedonia in PWH, leveraging ongoing studies and innovative experimental platforms.

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