Biomarkers of central and peripheral inflammation mediate the association between HIV and depressive symptoms

People living with HIV are at increased risk for depression, though mechanisms are unclear. In the general population, depression is associated with peripheral and central inflammation. Given that HIV elicits inflammation, the authors hypothesised that inflammatory biomarkers would partly mediate the association between HIV and depressive symptoms. People living with HIV (n = 125) and without HIV (n = 79) from the COBRA cohort were included; all with HIV were on antiretroviral therapy and virally suppressed. Plasma, CSF, and brain MR spectroscopy biomarkers were measured. Using logistic regression adjusted for sociodemographic factors, participants with HIV were more likely to have Any Depressive Symptoms (PHQ-9 >4) with an odds ratio [95% CI] of 3.72 [1.76, 8.09]. Sequential adjustment for each biomarker identified potential mediators (defined as >10% reduction in OR): plasma MIG (−15.0%) and TNF-α (−11.4%), and CSF MIP-1α (−21.0%) and IL-6 (−18.0%). No other soluble or neuroimaging biomarkers showed significant mediation. Findings suggest central and peripheral inflammatory biomarkers may partly explain the relationship between HIV and depressive symptoms.

Arish Muda Rakhasa-Loos, Nicholas Bakewell, David J. Sharp, Magnus Gisslén, Henrik Zetterberg, Jasmini Alagaratnam, Ferdinand W. N. M. Witte, Neeltje A. Kootstra, Alan Winston, Peter Reiss, Caroline A. Sabin, Jaime H. Vera