TY - JOUR
T1 - Biomarkers of central and peripheral inflammation mediate the association between HIV and depressive symptoms
AU - Mudra Rakshasa-Loots, Arish
AU - Bakewell, Nicholas
AU - Sharp, David J.
AU - Gisslén, Magnus
AU - Zetterberg, Henrik
AU - Alagaratnam, Jasmini
AU - Wit, Ferdinand W. N. M.
AU - on behalf of the COmorBidity in Relation to AIDS (COBRA) cohort
AU - Kootstra, Neeltje A.
AU - Winston, Alan
AU - Reiss, Peter
AU - Sabin, Caroline A.
AU - Vera, Jaime H.
N1 - Funding Information: AMRL thanks Simon Cox, Barbara Laughton, and Heather Whalley for scientific review and mentorship, and colleagues and friends at the University of Edinburgh (Mila Redžić, Reesha Zahir), Stellenbosch University, Brighton & Sussex Medical School, and Banaras Hindu University (Sulagna Basu) for continued support. Writing Group : Arish Mudra Rakshasa-Loots, Jaime H Vera, Nicholas Bakewell, Ferdinand W Wit, Neeltje A Kootstra, Alan Winston, Caroline A Sabin, and Peter Reiss. The COBRA Steering Committee : P Reiss (chair), A Winston, FW Wit, M Prins, MF Schim van der Loeff, J Schouten, B Schmand, GJ Geurtsen, DJ Sharp, MWA Caan, C Majoie, J Villaudy, B Berkhout, NA Kootstra, M Gisslén, A Pasternak, CA Sabin, G Guaraldi, A Bürkle, C Libert, C Franceschi, A Kalsbeek, E Fliers, J Hoeijmakers, J Pothof, M van der Valk, PH Bisschop, P Portegies, S Zaheri and D Burger. The COBRA Project Management Board : P Reiss, A Winston, FW Wit, JH Cole, MWA Caan, J Villaudy, NA Kootstra, MF Schim van der Loeff, M Gisslén, CA Sabin, A Bürkle and W Zikkenheiner. The Management Team : P Reiss, W Zikkenheiner, FW Wit, FR Janssen. The Clinical Cohort Team : A Winston, FW Wit, J Underwood, J Schouten, KW Kooij, RA van Zoest, N Doyle, M Prins, M Schim van der Loeff, P Portegies, BA Schmand, GJ Geurtsen, E Verheij, SO Verboeket, BC Elsenga, M van der Valk, S Zaheri, MMJ Hillebregt, YMC Ruijs, DP Benschop, L Tembo, L McDonald, M Stott, K Legg, A Lovell, O Erlwein, C Kingsley, P Norsworthy, S Mullaney, T Kruijer, L del Grande, V Olthof, GR Visser, L May, F Verbraak, N Demirkaya, I Visser, G Guaraldi. The Neuroimaging Team : DJ Sharp, MWA Caan, JH Cole, CBLM Majoie, T Su, R Leech, J Huguet. The HIS Mouse Study Team : J Villaudy, E Frankin, B Berkhout, A van der Kuyl, K Weijer, E Siteur-Van Rijnstra, D Burger, M de Graaff-Teulen. The Biomarker Team : NA Kootstra, M Gisslén, AM Harskamp-Holwerda, I Maurer, MM Mangas Ruiz, AF Girigorie, B Boeser-Nunnink, T Booiman, A Kalsbeek, PHLT Bisschop, D Burger, M de Graaff-Teulen, J Hoeijmakers, J Pothof, C Libert, S Dewaele, A Pasternak, C Franceschi, P Garagnani, C Pirazzini, M Capri, F Dall’Olio, M Chiricolo, S Salvioli, D Fuchs, H Zetterberg, D Weber, T Grune, EHJM Jansen. The Data Management and Analysis Team : N. Bakewell, CA Sabin, D De Francesco, FW Wit. The Dissemination Team : A Bürkle, T Sindlinger, S Oehlke, W Zikkenheiner, RA van Zoest. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - People living with HIV are at increased risk for depression, though the underlying mechanisms for this are unclear. 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 (n = 125) and without HIV (n = 79) 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 >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 >10% reduction in OR considered as evidence of potential mediation. Of the biomarkers analysed, MIG (−15.0%) and TNF-α (−11.4%) in plasma and MIP1-α (−21.0%) and IL-6 (−18.0%) 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.
AB - People living with HIV are at increased risk for depression, though the underlying mechanisms for this are unclear. 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 (n = 125) and without HIV (n = 79) 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 >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 >10% reduction in OR considered as evidence of potential mediation. Of the biomarkers analysed, MIG (−15.0%) and TNF-α (−11.4%) in plasma and MIP1-α (−21.0%) and IL-6 (−18.0%) 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.
UR - http://www.scopus.com/inward/record.url?scp=85161026997&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41398-023-02489-0
DO - https://doi.org/10.1038/s41398-023-02489-0
M3 - Article
C2 - 37280232
SN - 2158-3188
VL - 13
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 190
ER -