# Inflammation-Associated Mechanisms of Blood–Brain Barrier Disruption and Depression Pathogenesis in People with and Without HIV

## TL;DR

This review explores how chronic inflammation and blood-brain barrier disruption may contribute to depression in people with and without HIV.

## Contribution

The paper provides a comprehensive review of mechanisms linking inflammation, blood-brain barrier disruption, and depression in the context of HIV.

## Key findings

- Chronic inflammation and blood-brain barrier disruption are linked to depression in people with HIV.
- Blood-brain barrier permeability may mediate the effects of peripheral inflammation on the central nervous system.
- Current research suggests shared and unique pathways for depression in people with and without HIV.

## Abstract

Depression is the most common neuropsychiatric comorbidity in people with HIV (PWH), with a prevalence of 30–50%, nearly twice that of the general population. Depression is a major cause of disease burden worldwide associated with increased morbidity and mortality in both people with and without HIV. Converging lines of evidence indicate that chronic peripheral inflammation and neuroinflammation, blood–brain barrier (BBB) disruption, and neurocircuit-level changes interact to mediate depression pathogenesis, and that these processes may be especially relevant in PWH. HIV-associated chronic inflammation, which persists despite viral suppression with antiretroviral therapy, may contribute to depression pathogenesis in this population. BBB permeability has been hypothesized to serve as a key mediator for the interaction of peripheral inflammation with the central nervous system in depression pathogenesis. In this review, we will describe the structure and function of the BBB and how peripheral inflammation interacts with cells of the BBB and the mechanisms that lead to increased BBB permeability. We will discuss current research addressing how peripheral inflammation and BBB disruption contribute to depression pathogenesis in people with and without HIV. We will review current techniques for studying BBB permeability in in vitro, animal, and clinical models and outline future directions for ongoing research.