The following is a summary of “(NEURO)INFLAMMATORY BIOMARKERS MEDIATE THE ASSOCIATION BETWEEN HIV AND DEPRESSION”, presented by Arish Mudra Rakshasa-Loots, Nicholas Bakewell, David Sharp, Magnus Gisslen, Henrik Zetterberg, Jasmini Alagaratnam, Ferdinand Wit, Neeltje Kootstra, Alan Winston, Peter Reiss, Caroline Sabin, Jaime Vera

There is some evidence that people living with HIV have a higher risk of depression, but the reasons for this are not well understood. The general population shows a connection between depression and both local and systemic inflammation. Researchers hypothesized that (neuro)inflammatory biomarkers would mediate the link between HIV and depression since HIV infection may provoke (neuro)inflammation. HIV-positive and HIV-negative individuals from the COmorBidity in Relation to AIDS (COBRA) cohort were included. They used logistic regression to examine whether neuroimaging, blood, and cerebrospinal fluid (CSF) (neuro)inflammatory biomarkers might mediate the association between HIV status and Any Depression (Patient Health Questionnaire [PHQ-9] scores > 4). Before and following individual adjustment for each biomarker, they compared the odds ratio for any depression (OR, adjusted for age, sex, ethnicity, and level of education). Sample size variation was taken into consideration in all analyses. Potential mediators were defined as biomarkers with an OR decrease of 10% or more.

Participants having a PHQ-9 score and at least one biomarker were included (n = 204; 125 HIV-positive, 79 HIV-negative; median [IQR] age 57 years [51-62], 93% male, 92% White). The 2 groups started off with comparable characteristics. All HIV patients were taking antiretroviral drugs and had viral loads of less than 200 copies per milliliter of blood (mL). HIV-positive participants had a 26.4% greater prevalence of Any Depression compared to HIV-negative ones (P=0.02). When sociodemographic characteristics were taken into account but biomarkers were not, the OR (95% CI) for Any Depression in the entire sample (N = 204) was 3.27. (1.46, 8.09). When investigators looked at the biomarkers for depression, they found that plasma MIG (-15.0%), plasma TNF-α (-11.4%), CSF MIP1-α (-21.0%), and CSF IL-6 (-18.0%) all had ORs that were reduced by more than 10% when HIV status was taken into account.

The correlation between HIV status and depression in this population was mediated by MIG and TNF-α in plasma, and by MIP1- and IL-6 in cerebrospinal fluid. The findings suggest that distinct mechanisms constituting (neuro) inflammation may contribute to the increased risk of depression in HIV-positive individuals, as the biomarkers they examined are markers of inflammation (IL-6, TNF-α) and chemotaxis (MIP1-α, MIG). Noticable attenuation by the neuroimaging biomarkers was not observed, suggesting that this mediation may be driven at the periphery. Given the dearth of racial and gender diversity in this cohort, further research will require more comprehensive data sets.