Remitted depression and cognition in HIV: The role of cortisol and inflammation

Abstract

In major depressive disorder (MDD) and remitted MDD (rMDD) alterations in cortisol and inflammation are associated with cognitive difficulties, but these relationships have not been investigated in HIV. We used secondary data from a placebo-controlled, cross-over study of cognitive performance following a probe of the hypothalamic-pituitary-adrenal (HPA) axis (low dose hydrocortisone; LDH 10 mg) in 65 people with HIV (PWH; 36 women). Using placebo data, we examined sex-specific associations between two biomarkers - basal afternoon salivary cortisol and salivary inflammatory cytokines - cognition, and rMDD. Salivary cortisol and inflammatory biomarkers were sampled across the 5 -h study. The panel of inflammatory markers included interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor-(TNF)-α, CRP, interferon gamma-induced protein (IP-10), monocyte chemotactic protein (MCP)-1, monokine induced by interferon (MIG), matrix metalloproteinase MMP-9, and MMP-1. Learning, memory, attention/concentration, and executive function were assessed 30 min and 4 h after the placebo intervention; visuospatial ability was also assessed 30 min after the placebo intervention. For women but not men with HIV, basal cortisol concentrations were higher in rMDD versus noMDD groups, and related to poorer learning and memory. For men and women with HIV, basal inflammatory cytokines were higher in rMDD versus noMDD groups, but were negatively related to cognition independent of rMDD status. Cortisol and cytokines relate to cognition in PWH, but the associations depended on sex, rMDD status, and their interaction.

Keywords: Cognition; Cortisol; Depression; HIV; Inflammation.

Figure 1.

(A) Women with HIV and rMDD (n=18) have higher concentrations of endogenous salivary cortisol across the afternoon (p=0.03) and show elevated salivary inflammatory markers (median of 3 values between 12pm and 5pm) versus women with HIV and no MDD (n=18); (B) men with HIV and rMDD (n=15) and men with HIV and no MDD (n=30) have a similar profile of endogenous salivary cortisol across the afternoon (p=0.58). *P<0.05

Figure 2.

There is a strong association between basal salivary cortisol concentrations and (A) verbal learning and (B) memory among women with HIV and rMDD.

Figure 3.

Associations between salivary inflammatory markers and cognition in (A) women with HIV and (B) men with HIV Note. *P<0.10; ** P<0.05; *** P<0.01; Con=Congruent; Incon=incongruent; HVLT=Hopkins Verbal Learning Test; LNS=Letter Number Sequencing; TMT=Trail Making Test; JOLO=judgement of lines orientation