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

• Type of Material: Article
• Authors: Mandakh Bekhbat, Emory University; Christina Mehta, Emory University; Sean D. Kelly, Emory University; Aimee Vester, Emory University; Ighovwerha Ofotokun, Emory University; Jennifer Felger, Emory University; Gina Wingood, Emory University; Kathryn Anastos, Albert Einstein College of Medicine; Deborah R. Gustafson, State University of New York; Seble Kassaye, Georgetown University; Joel Milam, University of Southern California; Brad Aouizerat, New York University; Kathleen Weber, Cook County Health and Hospitals System; Elizabeth T. Golub, Johns Hopkins University; Michelle Floris Moore, University of North Carolina; Ralph Diclemente, Emory University; Margaret Fischl, University of Miami; Mirjam-Colette Kempf, University of Alabama Birmingham; Pauline Maki, University of Illinois; Gretchen Neigh, Emory University
• Language: English
• Date: 2018-10-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.psyneuen.2018.06.013
• Title of Journal or Parent Work: Psychoneuroendocrinology
• ISSN: 0306-4530
• Volume: 96
• Start Page: 118
• End Page: 125
• Grant/Funding Information: In addition, GNN was funded by K18 MH105098 and P30AI27767; Complete funding list available in full text.; The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID); with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the National Cancer Institute (NCI); the National Institute on Drug Abuse (NIDA); and the National Institute on Mental Health (NIMH).; WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA); UL1-TR000454 (Atlanta CTSA); and P30-AI-050410 (UNC CFAR).; Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR); the National Institute on Alcohol Abuse and Alcoholism (NIAAA); the National Institute on Deafness and other Communication Disorders (NIDCD); and the NIH Office of Research on Women’s Health.
• Keywords: Science & Technology; INFLAMMATION; Glucocorticoid; Inflammation; GENE-EXPRESSION; Depression; IMMUNOPHILINS; STRESS; MAJOR DEPRESSION; Endocrinology & Metabolism; FKBP5; Life Sciences & Biomedicine; RESISTANCE; Neurosciences; Psychiatry; RECEPTOR; INFECTED PATIENTS; Neurosciences & Neurology; Women; PATHOPHYSIOLOGY; HIV
• Research Categories: Psychology, Behavioral; Health Sciences, Medicine and Surgery

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.