Erythropoietin reduces neural and cognitive processing of fear in human models of antidepressant drug action.
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.
Miskowiak
Kamilla
K
Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, United Kingdom. kamilla.miskowiak@psy.ox.ac.uk
O'Sullivan
Ursula
U
Harmer
Catherine J
CJ
D000293:Adolescent; D000328:Adult; D000339:Affect; D000928:Antidepressive Agents / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D004311:Double-Blind Method; D004644:Emotions; D004911:Erythrocyte Volume; D004921:Erythropoietin / Q000494:pharmacology*; D005149:Facial Expression; D005239:Fear / Q000523:psychology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009778:Occipital Lobe / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010296:Parietal Lobe / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D021641:Recognition, Psychology / Q000187:drug effects
D000928:Antidepressive Agents; D004921:Erythropoietin; D010100:Oxygen