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In the general population, depression is associated with peripheral and central inflammation. Given this, and since HIV infection elicits inflammation, we hypothesised that peripheral and central inflammatory biomarkers would at least partly mediate the association between HIV and depressive symptoms. People living with HIV (<jats:italic>n<\/jats:italic>\u2009=\u2009125) and without HIV (<jats:italic>n<\/jats:italic>\u2009=\u200979) from the COmorBidity in Relation to AIDS (COBRA) cohort were included in this study. Participants living with and without HIV had similar baseline characteristics. All participants living with HIV were on antiretroviral therapy and were virally suppressed. Plasma, CSF, and brain MR spectroscopy (MRS) biomarkers were measured. Using logistic regression models adjusted for sociodemographic factors, we found that participants with HIV were more likely to have Any Depressive Symptoms (Patient Health Questionnaire [PHQ-9] score &gt;4) (odds ratio [95% confidence interval] 3.27 [1.46, 8.09]). We then sequentially adjusted the models for each biomarker separately to determine the mediating role of each biomarker, with a &gt;10% reduction in OR considered as evidence of potential mediation. Of the biomarkers analysed, MIG (\u221215.0%) and TNF-\u03b1 (\u221211.4%) in plasma and MIP1-\u03b1 (\u221221.0%) and IL-6 (\u221218.0%) in CSF mediated the association between HIV and depressive symptoms in this sample. None of the other soluble or neuroimaging biomarkers substantially mediated this association. Our findings suggest that certain biomarkers of central and peripheral inflammation may at least partly mediate the relationship between HIV and depressive symptoms.<\/jats:p>","DOI":"10.1038\/s41398-023-02489-0","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T17:24:04Z","timestamp":1686072244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biomarkers of central and peripheral inflammation mediate the association between HIV and depressive symptoms"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1860-3865","authenticated-orcid":false,"given":"Arish","family":"Mudra Rakshasa-Loots","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Bakewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Gissl\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmini","family":"Alagaratnam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2066-8115","authenticated-orcid":false,"given":"Ferdinand W. 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JA has received financial support to attend scientific conferences from MSD, Janssen UK and Gilead Sciences. HZ has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). MG has received research grants from Gilead Sciences and Janssen-Cilag and honoraria as speaker, DSMB committee member and\/or scientific advisor from Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline\/ViiV, Janssen-Cilag, MSD, Novocure, Novo Nordic, Pfizer and Sanofi. PR through his institution has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals Inc., Merck & Co and ViiV Healthcare, and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, and Merck & Co., for which honoraria were all paid to his institution. AW has received honoraria or research grants on behalf of Imperial College London or been a consultant or investigator in clinical trials sponsored by Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Roche and ViiV Healthcare. CAS has received funding for the membership of Data Safety and Monitoring Boards, Advisory Boards and for the preparation of educational materials from Gilead Sciences and ViiV Healthcare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"190"}}