Interferon-alpha-induced inflammation is associated with reduced glucocorticoid negative feedback sensitivity and depression in patients with hepatitis C virus

Jennifer C. Felger, Ebrahim Haroon, Bobbi J. Woolwine, Charles L Raison, Andrew H. Miller

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Major medical illnesses are associated with increased risk for depression and alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Pathophysiological processes such as inflammation that occur as a part of medical illnesses and their treatments have been shown to cause depressive symptoms, and may also affect the HPA axis. We previously reported that patients with hepatitis C virus chronically administered interferon (IFN)-alpha develop increased evening plasma cortisol concentrations and a flattened diurnal cortisol slope, which correlated with increased tumor necrosis factor (TNF) and its soluble receptor 2 (sTNFR2). Increased TNF and sTNFR2 were further correlated with depression and fatigue scores. The current study examined whether flattened cortisol slope might be secondary to reduced glucocorticoid receptor (GR) sensitivity, by measuring glucocorticoid negative feedback to dexamethasone (DEX) administration followed by corticotropin releasing hormone (CRH) challenge. In an exploratory analysis, 28 male and female patients with hepatitis C virus were studied at baseline (Visit 1) and after 12. weeks (Visit 2) of either IFN-alpha plus ribavirin (n = 17) or no treatment (n = 11). Patients underwent dexamethasone DEX-CRH challenge, neuropsychiatric assessments, and measurement of plasma TNF and sTNFR2 during each visit. IFN-alpha did not affect neuroendocrine responses following CRH but did increase post-DEX cortisol, which was correlated with flattening of the diurnal cortisol slope (r = 0.57, p = 0.002) and with increased depression scores (r = 0.38, p = 0.047). Furthermore, the change in post-DEX cortisol was associated with IFN-alpha-induced increase in sTNFR2 (r = 0.51, p = 006), which was in turn correlated with depression (r = 0.63, p.

Original languageEnglish (US)
JournalPhysiology and Behavior
DOIs
StateAccepted/In press - Aug 18 2015
Externally publishedYes

Keywords

  • Depression
  • Dexamethasone
  • Fatigue
  • Hepatitis C virus
  • HPA-axis
  • Inflammation

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Experimental and Cognitive Psychology
  • Philosophy

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