HIV and symptoms of depression are independently associated with impaired glucocorticoid signaling.
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.
['Bekhbat|Mandakh|M|', 'Mehta|C Christina|CC|', 'Kelly|Sean D|SD|', 'Vester|Aimee|A|', 'Ofotokun|Ighovwerha|I|', 'Felger|Jennifer|J|', 'Wingood|Gina|G|', 'Anastos|Kathryn|K|', 'Gustafson|Deborah R|DR|', 'Kassaye|Seble|S|', 'Milam|Joel|J|', 'Aouizerat|Bradley|B|', 'Weber|Kathleen|K|', 'Golub|Elizabeth T|ET|', 'Moore|Michelle Floris|MF|', 'Diclemente|Ralph|R|', 'Fischl|Margaret|M|', 'Kempf|Mirjam-Colette|MC|', 'Maki|Pauline|P|', 'Neigh|Gretchen N|GN|']
D000328:Adult D003430:Cross-Sectional Studies D003863:Depression D003907:Dexamethasone D005260:Female D005938:Glucocorticoids D006678:HIV D015658:HIV Infections D006801:Humans D015850:Interleukin-6 D008661:Metabolism, Inborn Errors D011569:Psychiatric Status Rating Scales D011965:Receptors, Glucocorticoid D015398:Signal Transduction D022021:Tacrolimus Binding Proteins D014409:Tumor Necrosis Factor-alpha
HIV Depression Glucocorticoid Inflammation Women FKBP5