title: The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study.
abstract: The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. 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) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU) or saline (0.9% NaCl) infusions in a double-blind, placebo-controlled, parallel--group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95% CI): EPO 10.94 ng/l (4.51-21.41 ng/l); mean increase at week 9: Saline 0.52 ng/l, p=0.04 (-5.88-4.48 ng/l) p=0.04, partial ŋ2=0.12). No significant effects were found on BDNF levels in partially remitted patients with BD (p=0.35). The present effects of EPO on BDNF levels in patients with TRD point to a role of neurotrophic factors in the potential effects of EPO seen in TRD and BD. The neurobiological mechanisms underlying these effects and the interaction between EPO and peripheral levels on BDNF need to be further elucidated in human studies including a broad range of biomarkers.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00916552.
authors.affiliation: Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.affiliation: Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Kamilla
authors.initials: K
authors.lastname: Miskowiak
authors.affiliation: Centre of Inflammation and Metabolism and Centre of Physical Activity Research, Rigshospitalet, 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Hoejman
authors.affiliation: Centre of Inflammation and Metabolism and Centre of Physical Activity Research, Rigshospitalet, 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Pedersen
authors.affiliation: Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D061218:Depressive Disorder, Treatment-Resistant / Q000097:blood / Q000188:drug therapy; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000097:blood* / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012074:Remission Induction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011994:Recombinant Proteins; D004921:Erythropoietin; C579455:BDNF protein, human