title: In patients with heart failure elevated soluble TNF-receptor 1 is associated with higher risk of depression.
abstract: BACKGROUND
  Pro-inflammatory cytokines may contribute to the development and progression of heart failure (HF) and are also implicated in depressive disorders. In this cross-sectional study, we investigated whether systemic inflammation, as assessed by circulating levels of inflammatory cytokines, was associated with comorbid depression in patients with heart failure.
  
  
  RESULTS
  Baseline clinical variables, depression status, and inflammatory marker levels were measured in 129 ambulatory HF patients. We hypothesized that pro-inflammatory cytokines, specifically tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6, would be elevated in HF patients with comorbid depression. In unadjusted analyses, levels of soluble TNF-alpha receptor1 (sTNFr1) were significantly higher among depressed (1.6 ng/mL), compared with nondepressed (1.1 ng/mL), HF patients (P = .01). After multivariate adjustment, compared with patients in the lowest quartile of sTNFr1 levels, those in the highest quartile had an adjusted near 5-fold higher risk of depression (OR 4.6, 95% CI 1.2-17.3; P for trend .008). The subgroup of patients on antidepressants but not currently depressed had a trend toward higher levels of sTNFr1, suggesting that antidepressants may not lower cytokine levels even when adequately treating depressive symptoms. IL-1beta and IL-6 levels were not significantly different among depressed versus nondepressed HF patients.
  
  
  CONCLUSIONS
  In this cross-sectional analysis, HF patients with comorbid depression, compared with nondepressed HF patients, had higher levels of sTNFr1 and trend toward higher levels of sTNFr1 even when adequately treated for depression.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Washington, Seattle, Washington, USA.
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Moorman
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
authors.forename: Charles W
authors.initials: CW
authors.lastname: Wilkinson
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lawler
authors.forename: George B
authors.initials: GB
authors.lastname: McDonald
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Crane
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.forename: Joan E
authors.initials: JE
authors.lastname: Russo
authors.forename: April S
authors.initials: AS
authors.lastname: Stempien-Otero
authors.forename: Mark D
authors.initials: MD
authors.lastname: Sullivan
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Levy
mesh_terms: D015897:Comorbidity; D003430:Cross-Sectional Studies; D016207:Cytokines; D003863:Depression / Q000097:blood / Q000503:physiopathology / Q000523:psychology*; D005260:Female; D006305:Health Status Indicators; D006333:Heart Failure / Q000097:blood* / Q000523:psychology; D006801:Humans; D007375:Interleukin-1; D015850:Interleukin-6; D008297:Male; D008875:Middle Aged; D011581:Psychological Tests; D011594:Psychometrics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I