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.Trial RegistrationClinicalTrials.gov: NCT00916552.
Highlights
Brain derived neurotrophic factor (BDNF) is a key target in the pathophysiology of neuropsychiatric disorders and the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity, neuronal survival and immune system regulation [1]
Mood symptoms were assessed with the Hamilton Depression Rating Scale 17-items (HDRS-17) [28], Beck Depression Inventory 21-items (BDI-21) [29], and for bipolar patients with the Young Mania Rating Scale (YMRS) [30] at baseline and weeks 5, 9, and 14
Eligible patients had an ICD-10 diagnosis of treatment resistant depression (TRD) (defined as failure to respond to adequate treatment with at least two different types of antidepressants given in adequate time and doses according to the Treatment Response to Antidepressants Questionnaire (TRAQ) [31]) were moderately to severely depressed (HDRS-17 score !17), or a diagnosis of Bipolar disorder (BD) in full or partial remission (HDRS-17 and YMRS scores 14) but with moderate to severe cognitive difficulties according to the Cognitive and Physical Functioning Questionnaire (CPFQ) [32]
Summary
Brain derived neurotrophic factor (BDNF) is a key target in the pathophysiology of neuropsychiatric disorders and the most widely distributed neurotrophin in the central nervous system where it plays several pivotal roles in synaptic plasticity, neuronal survival and immune system regulation [1]. Higher plasma BDNF levels seem to be associated with risk factors for cardiovascular disease including elevated diastolic blood pressure, higher cholesterol and higher BMI [15]. This suggests that the pattern of upand down regulation of BDNF is complex and may be mediated through interrelations between different growth factors regulating the central nervous system
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