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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\u2013brain 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.<\/jats:p>","DOI":"10.3390\/cells15050399","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:35:17Z","timestamp":1772022917000},"page":"399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inflammation-Associated Mechanisms of Blood\u2013Brain Barrier Disruption and Depression Pathogenesis in People with and Without HIV"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5024-5231","authenticated-orcid":false,"given":"Caitlin","family":"Hills","sequence":"first","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-7639","authenticated-orcid":false,"given":"Cristian A.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilma","family":"Gabbay","sequence":"additional","affiliation":[{"name":"Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA"},{"name":"Department of Psychiatry, University of Miami School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-4072","authenticated-orcid":false,"given":"Joan W.","family":"Berman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2026, January 19). 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