HIV and symptoms of depression are independently associated with impaired glucocorticoid signaling

Abstract

Chronic inflammation caused by HIV infection may lead to deficient glucocorticoid (GC) signaling predisposing people living with HIV to depression and other psychiatric disorders linked to GC resistance. We hypothesized that comorbid HIV and depressive symptoms in women would synergistically associate with deficits in GC signaling. This cross-sectional study used samples obtained from the Women's Interagency HIV Study (WIHS). The Centers for Epidemiological Studies (CES-D) was used to define depression in four groups of women from the Women's Interagency HIV Study (WIHS): 1) HIV-negative, non-depressed (n = 37); 2) HIV-negative, depressed (n = 34); 3) HIV-positive, non-depressed (n = 38); and 4) HIV-positive, depressed (n = 38). To assess changes in GC signaling from peripheral blood mononuclear cells (PBMCs), we examined baseline and dexamethasone (Dex)-stimulated changes in the expression of the GC receptor (GR, gene: Nr3c1) and its negative regulator Fkbp5 via quantitative RT-PCR. GR sensitivity was evaluated in vitro by assessing the Dex inhibition of lipopolysaccharide (LPS)-stimulated IL-6 and TNF-α levels. Depressive symptoms and HIV serostatus were independently associated with elevated baseline expression of Fkbp5 and Nr3c1. Depressive symptoms, but not HIV status, was independently associated with reduced LPS-induced release of IL-6. Counter to predictions, there was no interactive association of depressive symptoms and HIV on any outcome. Comorbid depressive symptoms with HIV infection were associated with a gene expression and cytokine profile similar to that of healthy control women, a finding that may indicate further disruptions in disease adaptation.

Higher levels of plasma inflammation biomarkers are associated with depressed mood and quality of life in aging, virally suppressed men, but not women, with HIV

“…Chronic HIV-associated inflammation and immune dysfunction have emerged as key factors that are strongly linked to non-AIDS complications ( Hsue et al., 2012 ; Deeks, 2011 ). Our findings confirm those of previous investigations ( Norcini Pala et al., 2016 ; Hellmuth et al., 2017 ; Musinguzi et al., 2018 ; McIntosh et al., 2018 ; Bekhbat et al., 2018 ), and extend them by evaluating a more comprehensive panel of biomarkers and more extensive evaluation of impact on daily functioning and quality of life. If the link between inflammation and depression is causal, our results suggest that treatment with selected anti-inflammatory medications might benefit mood and life quality in some PWH.…”

Sex Differences in Neurocognitive Function in Adults with HIV: Patterns, Predictors, and Mechanisms

“…2 Male/female differences in monocyte-associated inflammatory markers and less specific markers of inflammation among people living with and without HIV. HIV+, HIVseropositive; HIV-, HIVseronegative symptoms were independently associated with impaired glucocorticoid signaling [103]. How those alterations influence neurocognition is not yet elucidated but warrants further investigation.…”

HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice

“…As well, the β isoform of the GR, which inhibits the active α isoform of the receptor, may be increased by proinflammatory cytokines, thereby reducing GR signaling and promoting an increase in adrenal glucocorticoid [ 105 , 106 , 107 ]. Importantly, affective neuroHIV symptoms such as depression are associated with impaired GR signaling in HIV + women [ 108 ]. Another aspect of HPA dysregulation observed in HIV patients is adrenal insufficiency (observed in up to 46% patients [ 24 , 25 , 26 , 27 , 28 , 61 ]); however, we did not observe this in Tat-exposed females.…”