Original ArticleErythropoietin Reduces Neural and Cognitive Processing of Fear in Human Models of Antidepressant Drug Action
Section snippets
Subjects
Ethical approval for the study was obtained from the Oxfordshire Research Ethics Committee. Healthy subjects between 18 and 41 years were screened through a medical examination and psychiatric interview with the Structured Clinical Interview for DSM-Clinical Version (SCID-IV). Exclusion criteria were: current or past history of psychiatric disorder; any significant medical conditions (including diabetes, epilepsy, hypertension, and thrombosis); previous exposure to recombinant human
Biological Results
Analysis of blood samples before and after drug administration demonstrated no significant differences between the groups in the levels of Hb, hematocrit, or red cell count (all p > .3) (Table 1).
Mood and Subjective State
The two groups were well matched in terms of general mood, personality, and subjective state, indicated by the absence of significant baseline differences in BDI, EPQ, STAI, and VAS scores (all p > .05). Daily mood ratings on the BFS, VAS, and PANAS revealed no differences between groups over the week
Discussion
The present study demonstrated that one intravenous dose of Epo (40,000 IU) to healthy volunteers modulated the cognitive and neural processing of emotional information 1 week after administration. This is similar to effects of serotonergic and noradrenergic antidepressant drugs given to healthy volunteers and opposite to the negative biases reported in depression. Like known antidepressants, Epo modulated emotional responses in healthy volunteers without affecting mood during testing. The
Conclusions
In conclusion, the present study provides novel insights to the effects of Epo on the processing of emotional information in healthy humans. A single dose of Epo (40,000 IU) reduced the psychological and neural processing of fearful facial expressions 1 week after drug administration consistent with effects of antidepressant drugs in healthy volunteers, perhaps through different neurochemical mechanisms. This suggests that further characterization of the antidepressant actions of Epo in a
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2020, Progress in Neuro-Psychopharmacology and Biological PsychiatryCytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets
2018, Progress in Neuro-Psychopharmacology and Biological PsychiatryTesting the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action
2015, European NeuropsychopharmacologyCitation Excerpt :The observed trend-level effects on happy and disgust expressions were both in the same direction, which cannot be interpreted as an antidepressant-like effect. The reduced neural response to happy faces in the fusiform gyrus found in the ARA290 group, is the same region as reported by Miskowiak et al. (2007a) for EPO. However the direction of this effect was opposite: in Miskowiak et al. (2007a), EPO reduced the response to fearful vs neutral faces.
Comparison of the effects of erythropoietin and its carbamylated derivative on behaviour and hippocampal neurogenesis in mice
2011, NeuropharmacologyCitation Excerpt :Such a discrepancy could be due to differences in species (rat versus mice), the regimen of EPO administration (500 IU/kg daily over 4 days with the final dose administered shortly prior to testing), or the behavioural tests employed. In human, Miskowiak and colleagues have reported that the acute treatment of EPO in healthy subjects (Miskowiak et al., 2007c, 2008) and in patients with major depression (Miskowiak et al., 2009) modulated the neuronal processing of emotion in ways similar to anti-depressant agents. By contrast, we found that CEPO possesses antidepressant- and a trend towards anxiolytic-like properties.
Erythropoietin as neuroprotective and neuroregenerative treatment strategy: Comprehensive overview of 12 years of preclinical and clinical research
2010, Best Practice and Research: Clinical AnaesthesiologyCitation Excerpt :The same treatment schedule lastingly enhances higher brain functions in mice, ranging from various types of learning and memory processes to attentional performance.260 Interestingly, after only one single high intravenous dose of EPO, before any change in hematological readouts, healthy human subjects display alterations in functional MRI studies investigating the hippocampal response.261–263 Inspired by all these findings, we created a mouse model, overexpressing continuously active EPOR (i.e. an EPOR not requiring endogenous ligand) under the α-calcium/calmodulin-dependent protein kinase II (α-CaMKII) promoter.
Parts of this paper have been presented at summer meeting for British Association of Psychopharmacology, July 23–26, 2006.