title: Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders: A randomised controlled study.
abstract: OBJECTIVE
  This study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory.
  
  
  METHODS
  In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (sub-study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS)⩽14) (sub-study 2). In both sub-studies, patients were randomised in a double-blind, parallel-group design to receive eight weekly intravenous infusions of EPO (Eprex; 40,000IU/ml) or saline (0.9% NaCl). Plasma concentrations of interleukin 6 (IL-6), interleukin 18 (IL-18) and high sensitive c-reactive protein (hsCRP) were measured at week 1 (baseline) and weeks 5, 9 and 14. HDRS-17 and neuropsychological function was assessed at weeks 1, 9 and 14 using a test battery including the RAVLT Auditory Verbal Learning Test (primary depression and primary cognition outcomes in the original trial).
  
  
  RESULTS
  EPO had no cumulative effect on plasma levels of IL-6 or IL-18 but increased hsCRP levels in patients with TRD (mean±SD change in ng/L: EPO: 0.43±1.64; Saline: -0.90±2.43; F(1,39)=4.78, p=0.04). EPO had no effects on inflammatory markers in BD. There was no correlation between change in inflammatory markers and change in verbal memory.
  
  
  CONCLUSIONS
  Repeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory pathway is not a putative mechanism of the EPO-associated improvement of cognition in affective disorders.
authors.affiliation: Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: maj.vinberg@regionh.dk.
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.affiliation: Laboratory of Neuropsychiatry, Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Denmark. Electronic address: pia.weikop@regionh.dk.
authors.forename: Pia
authors.initials: P
authors.lastname: Weikop
authors.affiliation: Department of Neuroanaesthesia, The Neuroscience Centre, University Hospital of Copenhagen (Rigshospitalet) and Department of Neuroscience and Pharmacology, The Health Faculty, University of Copenhagen, Denmark. Electronic address: nvolsen@sund.ku.dk.
authors.forename: Niels Vidiendal
authors.initials: NV
authors.lastname: Olsen
authors.affiliation: Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: lars.vedel.kessing@regionh.dk.
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
authors.affiliation: Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: kamilla.miskowiak@regionh.dk.
authors.forename: Kamilla
authors.initials: K
authors.lastname: Miskowiak
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism*; D061218:Depressive Disorder, Treatment-Resistant / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000188:drug therapy*; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011994:Recombinant Proteins
chemical_list: C508600:IL6 protein, human; D020382:Interleukin-18; D015850:Interleukin-6; D011994:Recombinant Proteins; D004921:Erythropoietin; D002097:C-Reactive Protein
keywords: Affective disorder; Cognition; Erythropoietin; Inflammatory markers