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Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients

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Abstract

Objective

Erythropoietin (Epo) has neuroprotective and neurotrophic effects, and may be a novel therapeutic agent in the treatment of psychiatric disorders. We have demonstrated antidepressant-like effects of Epo on the neural and cognitive processing of facial expressions in healthy volunteers. The current study investigates the effects of Epo on the neural and cognitive response to emotional facial expressions in depressed patients.

Method

Nineteen acutely depressed patients were randomized to receive Epo (40,000 IU) or saline intravenously in a double-blind, parallel-group design. On day 3, we assessed neuronal responses to fearful and happy faces using functional magnetic resonance imaging and measured facial expression recognition after the scan.

Results

Epo reduced neural response to fearful vs. happy faces in the amygdala and hippocampus, and to fearful faces vs. baseline in superior temporal and occipitoparietal regions 3 days after administration in acutely depressed patients. This was accompanied by a specific reduction in the recognition of fear in Epo-treated patients after the scan similar to the effects on face recognition seen with antidepressant drug treatment.

Conclusions

The present findings are similar to the effects of conventional antidepressants in acutely depressed patients and opposite to hypervigilance to negative facial expressions in depression. This highlights a potential antidepressant mechanism and warrants further investigation of Epo as a new candidate compound for treatment of depression.

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Acknowledgements

This study was supported by the Lundbeck Foundation, Denmark (grant no. 94/04).

Disclosures

Drs. Miskowiak, Favaron, Hafizi, and Inkster report no competing interests. Dr. Miskowiak has received grant support from the Economic and Social Research Council, University of Oxford, and the Lundbeck Foundation, Denmark. Dr. Inkster is funded by Imperial College, London. Professor Goodwin has received honoraria from AstraZeneca, BMS, Eisai, Lundbeck, Sanofi-Aventis, and Servier; has acted as advisor for AstraZeneca, BMS, Lilly, Lundbeck, P1Vital, Sanofi-Aventis, Servier, and Wyeth; holds share options in P1vital; and has acted as an expert witness for Eli Lilly. Professor Goodwin has also received grants from Bailly Thomas Fund, MRC, and Stanley MRI. Professsor Cowen has served as a paid member of advisory boards for DSM, Eli Lilly, Sevier, Wyeth, and Xytis. Dr. Harmer has received grant support from the Medical Research Council, University of Oxford, Merck, Sharpe, and Dohme; has acted as a consultant for Lundbeck, Merck, Sharpe, Dohme, Servier, GSK, and P1Vital; and also holds shares in P1vital.

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Authors and Affiliations

  1. Department of Psychiatry, Copenhagen University Hospital, Hans Kirks Vej 6, DK-2200, Copenhagen, Denmark

    Kamilla W. Miskowiak

  2. Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, United Kingdom

    Kamilla W. Miskowiak, Elisa Favaron, Sepehr Hafizi, Guy M. Goodwin, Philip J. Cowen & Catherine J. Harmer

  3. Division of Neuroscience and Mental Health, Imperial College London, London, SW7 2AZ, United Kingdom

    Becky Inkster

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  1. Kamilla W. Miskowiak
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  2. Elisa Favaron
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  3. Sepehr Hafizi
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  4. Becky Inkster
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  5. Guy M. Goodwin
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  6. Philip J. Cowen
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  7. Catherine J. Harmer
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Correspondence to Kamilla W. Miskowiak.

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Miskowiak, K.W., Favaron, E., Hafizi, S. et al. Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients. Psychopharmacology 210, 419–428 (2010). https://doi.org/10.1007/s00213-010-1842-7

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  • DOI: https://doi.org/10.1007/s00213-010-1842-7

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