1. ¹Department of Experimental Psychology, University of Oxford, Oxford, UK
2. ²Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK
3. ³Department of Clinical Neurology, FMRIB Centre, John Radcliffe Hospital, Oxford University, Oxford, UK

Correspondence: K Miskowiak, Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford OX3 7JX, UK. Tel: +44 0 1865 233612; Fax: + 44 0 1865 251076; E-mail: kamilla.miskowiak@psy.ox.ac.uk

Received 2 February 2007; Revised 27 March 2007; Accepted 29 March 2007; Published online 2 May 2007.

Abstract

Erythropoietin (Epo) has neuroprotective and neurotrophic effects and is a promising candidate for treatment of neurodegenerative and psychiatric disorder. Recently, we demonstrated that Epo modulates memory-relevant hippocampal response and fear processing in human models of antidepressant drug action 1 week post-administration, and improves self-reported mood for 3 days immediately following administration. The present study explored the effects of Epo (40 000 IU) vs saline on self-reported mood and on neural and cognitive function in healthy volunteers 3 days post-administration to test the reliability of the rapid mood improvement and its neuropsychological basis. Neuronal responses during the processing of happy and fearful faces were investigated using functional magnetic resonance imaging (fMRI); facial expression recognition performance was assessed after the fMRI scan. Daily ratings of mood were obtained for 3 days after Epo/saline administration. During faces processing Epo enhanced activation in the left amygdala and right precuneus to happy and fearful expressions. This was paired with improved recognition of all facial expressions, in particular of low intensity happiness and fear. This is similar to behavioral effects observed with acute administration of serotonergic antidepressants. Consistent with our previous finding, Epo improved self-reported mood for all 3 days post-administration. Together, these results suggest that characterization of the effects of Epo in a clinically depressed group is warranted.