Elsevier

Biological Psychiatry

Volume 62, Issue 11, 1 December 2007, Pages 1244-1250
Biological Psychiatry

Original Article
Erythropoietin Reduces Neural and Cognitive Processing of Fear in Human Models of Antidepressant Drug Action

https://doi.org/10.1016/j.biopsych.2007.01.011Get rights and content

Background

Erythropoietin (Epo) has neuroprotective and neurotrophic effects in animal models and affects cognitive and associated neural responses in humans. These effects have highlighted Epo as a candidate for treatment of psychiatric disease including schizophrenia and depression. The current study aimed to explore the effects of Epo on neural and behavioral measures of emotional processing relevant for depression and the effects of conventional antidepressant medication.

Methods

In the present study, we used functional magnetic resonance imaging to explore the effects of Epo (40,000 IU) versus saline on the neural processing of happy and fearful faces in 23 healthy volunteers. Facial expression recognition was assessed outside the scanner.

Results

One week after administration, Epo reduced neural response to fearful versus neutral faces in the occipito-parietal cortex consistent with reduced attention to fear. Erythropoietin additionally reduced recognition of fearful facial expressions without affecting recognition of other emotional expressions. These actions occurred in the absence of changes in hematological parameters.

Conclusions

The present study demonstrates that Epo directly modulates brain responses to emotional information in humans in a manner consistent with the actions of conventional antidepressants. The characterization of the effects of Epo in a clinically depressed group is therefore warranted.

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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