Effects of erythropoietin on emotional processing biases in patients with major depression: an exploratory fMRI study.
BACKGROUND
Erythropoietin (Epo) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression. We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers.


OBJECTIVE
The current study aimed to explore the effects of Epo on the neural processing of emotional information in depressed patients.


METHODS
Seventeen patients with acute major depressive disorder were randomised to receive Epo (40,000 IU) or saline iv in a double-blind, parallel-group design. On day 3, we assessed neural responses to positive, negative and neutral pictures during fMRI followed by picture recall after the scan. Mood and blood parameters were assessed at baseline and on day 3.


RESULTS
Epo reduced neural response to negative vs. positive pictures 3 days post-administration in a network of areas including the hippocampus, ventromedial prefrontal and parietal cortex. After the scan, Epo-treated patients showed improved memory compared with those that were given placebo. The effects occurred in the absence of changes in mood or haematological parameters, suggesting that they originated from direct neurobiological actions of Epo.


CONCLUSIONS
These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression. The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism.
Miskowiak
Kamilla W
KW
Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark. kamilla@miskowiak.dk
Favaron
Elisa
E
Hafizi
Sepehr
S
Inkster
Becky
B
Goodwin
Guy M
GM
Cowen
Philip J
PJ
Harmer
Catherine J
CJ
D000328:Adult; D000928:Antidepressive Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D015982:Bias; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects*; D004921:Erythropoietin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D005149:Facial Expression; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation / Q000379:methods; D011930:Reaction Time; D021641:Recognition, Psychology / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
D000928:Antidepressive Agents; D004921:Erythropoietin; D010100:Oxygen
Br Med J (Clin Res Ed). 1986 Feb 1;292(6516):344
3080166
Brain. 2007 Oct;130(Pt 10):2577-88
17728357
BMC Biol. 2008 Sep 09;6:37
18782446
Neuroimage. 2004 Apr;21(4):1732-47
15050594
J Biol Chem. 2007 Aug 31;282(35):25875-83
17604282
Mol Psychiatry. 2007 Feb;12(2):206-20
17033631
Psychophysiology. 2003 Sep;40(5):655-65
14696720
Psychiatr Clin North Am. 2004 Mar;27(1):19-36, vii-viii
15062628
Nat Rev Neurosci. 2006 Feb;7(2):137-51
16429123
Neuroimage. 2006 Jun;31(2):906-19
16488159
Arch Gen Psychiatry. 1961 Jun;4:561-71
13688369
Biol Psychiatry. 2008 Jun 15;63(12):1155-62
18281017
Psychopharmacology (Berl). 2008 Sep;199(4):503-13
18581100
Psychiatry Res. 1999 Oct 11;91(3):127-39
10641577
Prog Brain Res. 2006;156:67-91
17015075
J Neurosci. 2007 Mar 14;27(11):2788-92
17360900
Biol Psychiatry. 2006 Nov 1;60(9):974-86
16780808
Neuroreport. 1998 Oct 5;9(14):3253-8
9831460
Psychiatr Prax. 2004 Nov;31 Suppl 1:S70-2
15570508
Hum Brain Mapp. 2000 Jul;10(3):120-31
10912591
J Psychopharmacol. 2005 Nov;19(6):565-6
16272178
J Pers Soc Psychol. 1988 Jun;54(6):1063-70
3397865
Neuropsychopharmacology. 2003 Jan;28(1):148-52
12496951
Neuropharmacology. 2008 Nov;55(6):1023-8
18634807
Neuroimage. 2007 Sep 1;37(3):904-11
17625917
Biol Psychiatry. 2000 Oct 15;48(8):813-29
11063977
J Neurosci. 1996 Jul 1;16(13):4207-21
8753882
Neuropsychopharmacology. 2008 Feb;33(3):611-8
17473836
Mod Probl Pharmacopsychiatry. 1974;7(0):189-202
4413308
Neuroimage. 2003 Jul;19(3):1233-9
12880848
J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62
14399272
Biol Psychiatry. 2006 May 1;59(9):816-20
16460693
Mol Psychiatry. 2008 Nov;13(11):1011-20
17955021
Neuroimage. 2001 Dec;14(6):1370-86
11707093
J Neurochem. 2005 Apr;93(2):412-21
15816864
Lancet. 1997 May 17;349(9063):1436-42
9164317
Nat Rev Neurosci. 2005 Jun;6(6):484-94
15928718
Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10526-31
10984541
Biol Psychiatry. 2007 Dec 1;62(11):1244-50
17553466
Behav Res Ther. 1995 Sep;33(7):755-70
7677713
Br J Psychiatry. 1982 Nov;141:518-23
7150890