The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study

TY - JOUR

T1 - The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders

T2 - a randomised controlled study

AU - Vinberg, Maj

AU - Miskowiak, Kamilla

AU - Hoejman, Pernille

AU - Pedersen, Maria

AU - Kessing, Lars Vedel

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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 2=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.

AB - 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 2=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.

U2 - 10.1371/journal.pone.0127629

DO - 10.1371/journal.pone.0127629

M3 - Journal article

C2 - 26011424

SN - 1932-6203

SP - 1

EP - 16

JO - PLoS Computational Biology

JF - PLoS Computational Biology

M1 - e0127629

ER -