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Erythropoietin: a candidate treatment for mood symptoms and memory dysfunction in depression

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Abstract

Objective

Current pharmacological treatments for depression have a significant treatment-onset-response delay, an insufficient efficacy for many patients and fail to reverse cognitive dysfunction. Erythropoietin (EPO) has neuroprotective and neurotrophic actions and improves cognitive function in animal models of acute and chronic neurodegenerative conditions and in patients with cognitive decline.

Methods

We systematically reviewed the published findings from animal and human studies exploring the potential of EPO to treat depression-related cognitive dysfunction and depression.

Results

We identified five animal studies (two in male rats, two in male mice and one in male rats and mice) and seven human proof-of-concept studies (five in healthy volunteers and two in depressed patients) that investigated the above. All of the reviewed animal studies but one and all human studies demonstrated beneficial effects of EPO on hippocampus-dependent memory and antidepressant-like effects. These effects appear to be mediated through direct neurobiological actions of EPO rather than upregulation of red cell mass.

Conclusions

The reviewed studies demonstrate beneficial effects of EPO on hippocampus-dependent memory function and on depression-relevant behavior, thus highlighting EPO as a candidate agent for future management of cognitive dysfunction and mood symptoms in depression. Larger-scale clinical trials of EPO as a treatment for mood and neurocognitive symptoms in patients with mood disorder are therefore warranted.

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References

  • Adamcio B, Sargin D, Stradomska A, Medrihan L, Gertler C, Theis F et al (2008) Erythropoietin enhances hippocampal long-term potentiation and memory. BMC Biol 6:37

    Article  PubMed  Google Scholar 

  • Agnello D, Bigini P, Villa P, Mennini T, Cerami A, Brines ML et al (2002) Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain Res 952:128–134

    Article  PubMed  CAS  Google Scholar 

  • Aimone JB, Wiles J, Gage FH (2006) Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9:723–727

    Article  PubMed  CAS  Google Scholar 

  • Baldessarini RJ (1989) Current status of antidepressants: clinical pharmacology and therapy. J Clin Psychiatry 50:117–126

    PubMed  CAS  Google Scholar 

  • Behnken A, Schoning S, Gerss J, Konrad C, de Jong-Meyer R, Zwanzger P et al (2010) Persistent non-verbal memory impairment in remitted major depression—caused by encoding deficits? J Affect Disord 122:144–148

    Article  PubMed  Google Scholar 

  • Belmaker RH, Agam G (2008) Mechanisms of disease: major depressive disorder. N Engl J Med 358:55–68

    Article  PubMed  CAS  Google Scholar 

  • Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:137–151

    Article  PubMed  CAS  Google Scholar 

  • Bierer R, Peceny MC, Hartenberger CH, Ohls RK (2006) Erythropoietin concentrations and neurodevelopmental outcome in preterm infants. Pediatrics 118:e635–e640

    Article  PubMed  Google Scholar 

  • Biringer E, Mykletun A, Sundet K, Kroken R, Stordal KI, Lund A (2007) A longitudinal analysis of neurocognitive function in unipolar depression. J Clin Exp Neuropsychol 29:879–891

    Article  PubMed  Google Scholar 

  • Boran BO, Colak A, Kutlay M (2005) Erythropoietin enhances neurological recovery after experimental spinal cord injury. Restor Neurol Neurosci 23:341–345

    PubMed  CAS  Google Scholar 

  • Borcel E, Perez-Alvarez L, Herrero AI, Brionne T, Varea E, Berezin V et al (2008) Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule. Behav Pharmacol 19:41–49

    Article  PubMed  Google Scholar 

  • Bouhuys AL, Geerts E, Gordijn MC (1999) Depressed patients' perceptions of facial emotions in depressed and remitted states are associated with relapse: a longitudinal study. J Nerv Ment Dis 187:595–602

    Article  PubMed  CAS  Google Scholar 

  • Bradley BP, Mogg K, Williams R (1995) Implicit and explicit memory for emotion-congruent information in clinical depression and anxiety. Behav Res Ther 33:755–770

    Article  PubMed  CAS  Google Scholar 

  • Brines M, Cerami A (2005) Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci 6:484–494

    Article  PubMed  CAS  Google Scholar 

  • Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C et al (2000) Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A 97:10526–10531

    Article  PubMed  CAS  Google Scholar 

  • Britton JC, Taylor SF, Sudheimer KD, Liberzon I (2006) Facial expressions and complex IAPS pictures: common and differential networks. Neuroimage 31:906–919

    Article  PubMed  Google Scholar 

  • Brown MS, Eichorst D, Lala-Black B, Gonzalez R (2009) Higher cumulative doses of erythropoietin and developmental outcomes in preterm infants. Pediatrics 124:e681–e687

    Article  PubMed  Google Scholar 

  • Byts N, Siren AL (2009) Erythropoietin: a multimodal neuroprotective agent. Exp Transl Stroke Med 1:4

    Article  PubMed  Google Scholar 

  • Campbell S, Macqueen G (2004) The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci 29:417–426

    PubMed  Google Scholar 

  • Cansino S, Maquet P, Dolan RJ, Rugg MD (2002) Brain activity underlying encoding and retrieval of source memory. Cereb Cortex 12:1048–1056

    Article  PubMed  Google Scholar 

  • Castilla-Ortega E, Pedraza C, Estivill-Torrus G, Santin LJ (2011) When is adult hippocampal neurogenesis necessary for learning? Evidence from animal research. Rev Neurosci 22:267–283

    Article  PubMed  Google Scholar 

  • Chambers RA, Potenza MN, Hoffman RE, Miranker W (2004) Simulated apoptosis/neurogenesis regulates learning and memory capabilities of adaptive neural networks. Neuropsychopharmacology 29:747–758

    Article  PubMed  Google Scholar 

  • Ding G, Jiang Q, Li L, Zhang L, Wang Y, Zhang ZG et al (2010) Cerebral tissue repair and atrophy after embolic stroke in rat: a magnetic resonance imaging study of erythropoietin therapy. J Neurosci Res 88:3206–3214

    Article  PubMed  CAS  Google Scholar 

  • Drevets WC (2003) Neuroimaging abnormalities in the amygdala in mood disorders. Ann N Y Acad Sci 985:420–444

    Article  PubMed  Google Scholar 

  • Dulawa SC, Hen R (2005) Recent advances in animal models of chronic antidepressant effects: the novelty-induced hypophagia test. Neurosci Biobehav Rev 29:771–783

    Article  PubMed  CAS  Google Scholar 

  • Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    Article  PubMed  CAS  Google Scholar 

  • Duman RS, Malberg J, Thome J (1999) Neural plasticity to stress and antidepressant treatment. Biol Psychiatry 46:1181–1191

    Article  PubMed  CAS  Google Scholar 

  • Ehrenreich H, Degner D, Meller J, Brines M, Behe M, Hasselblatt M et al (2004) Erythropoietin: a candidate compound for neuroprotection in schizophrenia. Mol Psychiatry 9:42–54

    PubMed  CAS  Google Scholar 

  • Ehrenreich H, Fischer B, Norra C, Schellenberger F, Stender N, Stiefel M et al (2007a) Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain 130:2577–2588

    Article  PubMed  Google Scholar 

  • Ehrenreich H, Hinze-Selch D, Stawicki S, Aust C, Knolle-Veentjer S, Wilms S et al (2007b) Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry 12:206–220

    Article  PubMed  CAS  Google Scholar 

  • El-Kordi A, Radyushkin K, Ehrenreich H (2009) Erythropoietin improves operant conditioning and stability of cognitive performance in mice. BMC Biol 7:37

    Article  PubMed  Google Scholar 

  • Erbayraktar S, Grasso G, Sfacteria A, Xie QW, Coleman T, Kreilgaard M et al (2003) Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo. Proc Natl Acad Sci U S A 100:6741–6746

    Article  PubMed  CAS  Google Scholar 

  • Erickson K, Drevets W, Schulkin J (2003) Glucocorticoid regulation of diverse cognitive functions in normal and pathological emotional states. Neurosci Biobehav Rev 27:233–246

    Article  PubMed  CAS  Google Scholar 

  • Eriksson TM, Delagrange P, Spedding M, Popoli M, Mathe AA, Ogren SO et al (2011) Emotional memory impairments in a genetic rat model of depression: involvement of 5-HT/MEK/Arc signaling in restoration. Mol Psychiatry

  • Garcia-Rodriguez JC, Sosa-Teste I (2009) The nasal route as a potential pathway for delivery of erythropoietin in the treatment of acute ischemic stroke in humans. Sci World J 9:970–981

    Article  Google Scholar 

  • Genc S, Zadeoglulari Z, Oner MG, Genc K, Digicaylioglu M (2011) Intranasal erythropoietin therapy in nervous system disorders. Expert Opin Drug Deliv 8:19–32

    Article  PubMed  CAS  Google Scholar 

  • Giacobbe P, Mayberg HS, Lozano AM (2009) Treatment resistant depression as a failure of brain homeostatic mechanisms: implications for deep brain stimulation. Exp Neurol 219:44–52

    Article  PubMed  Google Scholar 

  • Girgenti MJ, Hunsberger J, Duman CH, Sathyanesan M, Terwilliger R, Newton SS (2009) Erythropoietin induction by electroconvulsive seizure, gene regulation, and antidepressant-like behavioral effects. Biol Psychiatry 66:267–274

    Article  PubMed  CAS  Google Scholar 

  • Hamilton JP, Gotlib IH (2008) Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biol Psychiatry 63:1155–1162

    Article  PubMed  Google Scholar 

  • Hariri AR, Goldberg TE, Mattay VS, Kolachana BS, Callicott JH, Egan MF et al (2003) Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J Neurosci 23:6690–6694

    PubMed  CAS  Google Scholar 

  • Harmer CJ (2010) Antidepressant drug action: a neuropsychological perspective. Depress Anxiety 27:231–233

    Article  PubMed  Google Scholar 

  • Harmer CJ, Bhagwagar Z, Perrett DI, Vollm BA, Cowen PJ, Goodwin GM (2003) Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology 28:148–152

    Article  PubMed  CAS  Google Scholar 

  • Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM (2004) Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry 161:1256–1263

    Article  PubMed  Google Scholar 

  • Harmer CJ, Mackay CE, Reid CB, Cowen PJ, Goodwin GM (2006) Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biol Psychiatry 59:816–820

    Article  PubMed  CAS  Google Scholar 

  • Harmer CJ, Cowen PJ, Goodwin GM (2010) Efficacy markers in depression. J Psychopharmacol

  • Hasselbalch J, Hasselbalch SG, Gade A, Knorr UB, Kessing LV (2010) Cognitive function in the remitted state of unipolar disorder and the association with the course of illness. In.

  • Herbert J (2008) Neurogenesis and depression: breakthrough or blind alley? J Neuroendocrinol 20:413–414

    Article  PubMed  CAS  Google Scholar 

  • Jacobson LO, Goldwasser E, Fried W, Plzak LF (1957) Studies on erythropoiesis. VII. The role of the kidney in the production of erythropoietin. In. pp 305–317.

  • Jelkmann W (1992) Erythropoietin: structure, control of production, and function. Physiol Rev 72:449–489

    PubMed  CAS  Google Scholar 

  • Jelkmann W, Bohlius J, Hallek M, Sytkowski AJ (2008) The erythropoietin receptor in normal and cancer tissues. Crit Rev Oncol Hematol 67:39–61

    Article  PubMed  Google Scholar 

  • Kessing LV (1998) Cognitive impairment in the euthymic phase of affective disorder. Psychol Med 28:1027–1038

    Article  PubMed  CAS  Google Scholar 

  • Kitraki E, Kremmyda O, Youlatos D, Alexis M, Kittas C (2004) Spatial performance and corticosteroid receptor status in the 21-day restraint stress paradigm. Ann N Y Acad Sci 1018:323–327

    Article  PubMed  CAS  Google Scholar 

  • Kumral A, Ozer E, Yilmaz O, Akhisaroglu M, Gokmen N, Duman N et al (2003) Neuroprotective effect of erythropoietin on hypoxic-ischemic brain injury in neonatal rats. Biol Neonate 83:224–228

    Article  PubMed  CAS  Google Scholar 

  • Lang PJ, Bradley MM, Cuthbert BN (1997) International Affective Picture System (IAPS): technical manual and affective ratings. In: NIMH Center for the Study of Emotion and Attention. University of Florida, Gainesville FL

  • Leconte C, Bihel E, Lepelletier FX, Bouet V, Saulnier R, Petit E et al (2011) Comparison of the effects of erythropoietin and its carbamylated derivative on behaviour and hippocampal neurogenesis in mice. Neuropharmacology 60:354–364

    Article  PubMed  CAS  Google Scholar 

  • Leist M, Ghezzi P, Grasso G, Bianchi R, Villa P, Fratelli M et al (2004) Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305:239–242

    Article  PubMed  CAS  Google Scholar 

  • Lembke A, Ketter TA (2002) Impaired recognition of facial emotion in mania. Am J Psychiatry 159:302–304

    Article  PubMed  Google Scholar 

  • Li W, Maeda Y, Yuan RR, Elkabes S, Cook S, Dowling P (2004) Beneficial effect of erythropoietin on experimental allergic encephalomyelitis. Ann Neurol 56:767–777

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, de LM, de SS, Convit A, Tarshish C, Nair NP et al (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1:69–73

  • Manji HK, Moore GJ, Rajkowska G, Chen G (2000) Neuroplasticity and cellular resilience in mood disorders. Mol Psychiatry 5:578–593

    Article  PubMed  CAS  Google Scholar 

  • Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, A Gray N et al (2003) Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 53:707–742

  • Marti HH, Wenger RH, Rivas LA, Straumann U, Digicaylioglu M, Henn V, et al (1996) Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci. 8(4):666–676

    Google Scholar 

  • Martinez-Aran A, Vieta E, Colom F, Torrent C, Sanchez-Moreno J, Reinares M et al (2004) Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome. Bipolar Disord 6:224–232

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54:20–23

    Article  PubMed  CAS  Google Scholar 

  • Meyer JW, Eichhorn KH, Vetter K, Christen S, Schleusner E, Klos A et al (1995) Does recombinant human erythropoietin not only treat anemia but reduce postpartum (emotional) distress as well? J Perinat Med 23:99–109

    Article  PubMed  CAS  Google Scholar 

  • Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741

    Article  PubMed  CAS  Google Scholar 

  • Miskowiak K, Inkster B, Selvaraj S, Goodwin G, Harmer C (2007a) Erythropoietin has no effect on hippocampal response during memory retrieval 3 days post-administration. Psychopharmacology (Berl) 195:451–453

    Article  CAS  Google Scholar 

  • Miskowiak K, O’Sullivan U, Harmer CJ (2007b) Erythropoietin enhances hippocampal response during memory retrieval in humans. J Neurosci 27:2788–2792

    Article  PubMed  CAS  Google Scholar 

  • Miskowiak K, O’Sullivan U, Harmer CJ (2007c) Erythropoietin reduces neural and cognitive processing of fear in human models of antidepressant drug action. Biol Psychiatry 62:1244–1250

    Article  PubMed  CAS  Google Scholar 

  • Miskowiak K, Inkster B, O’Sullivan U, Selvaraj S, Goodwin GM, Harmer CJ (2008a) Differential effects of erythropoietin on neural and cognitive measures of executive function 3 and 7 days post-administration. Exp Brain Res 184:313–321

    Article  PubMed  CAS  Google Scholar 

  • Miskowiak K, Inkster B, Selvaraj S, Wise R, Goodwin GM, Harmer CJ (2008b) Erythropoietin improves mood and modulates the cognitive and neural processing of emotion 3 days post administration. Neuropsychopharmacology 33:611–618

    Article  PubMed  CAS  Google Scholar 

  • Miskowiak KW, Favaron E, Hafizi S, Inkster B, Goodwin GM, Cowen PJ et al (2009) Effects of erythropoietin on emotional processing biases in patients with major depression: an exploratory fMRI study. Psychopharmacology (Berl) 207:133–142

    Article  CAS  Google Scholar 

  • Miskowiak KW, Favaron E, Hafizi S, Inkster B, Goodwin GM, Cowen PJ et al (2010a) Erythropoietin modulates neural and cognitive processing of emotional information in biomarker models of antidepressant drug action in depressed patients. Psychopharmacology (Berl) 210:419–428

    Article  CAS  Google Scholar 

  • Miskowiak KW, Vinberg M, Harmer CJ, Ehrenreich H, Knudsen GM, Macoveanu J et al (2010b) Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder. Trials 11:97

    Article  PubMed  Google Scholar 

  • Miu AC, Olteanu AI, Chis I, Heilman RM (2004) Have no fear, erythropoietin is here: erythropoietin protects fear conditioning performances after functional inactivation of the amygdala. Behav Brain Res 155:223–229

    Article  PubMed  CAS  Google Scholar 

  • Mogensen J, Miskowiak K, Sorensen TA, Lind CT, Olsen NV, Springborg JB et al (2004) Erythropoietin improves place learning in fimbria-fornix-transected rats and modifies the search pattern of normal rats. Pharmacol Biochem Behav 77:381–390

    Article  PubMed  CAS  Google Scholar 

  • Morishita E, Masuda S, Nagao M, Yasuda Y, Sasaki R (1997) Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience 76:105–116

    Article  PubMed  CAS  Google Scholar 

  • Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B (2007) Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet 370:851–858

    Article  PubMed  Google Scholar 

  • Neubauer AP, Voss W, Wachtendorf M, Jungmann T (2010) Erythropoietin improves neurodevelopmental outcome of extremely preterm infants. Ann Neurol 67:657–666

    PubMed  CAS  Google Scholar 

  • Paradiso S, Lamberty GJ, Garvey MJ, Robinson RG (1997) Cognitive impairment in the euthymic phase of chronic unipolar depression. J Nerv Ment Dis 185:748–754

    Article  PubMed  CAS  Google Scholar 

  • Pickett JL, Theberge DC, Brown WS, Schweitzer SU, Nissenson AR (1999) Normalizing hematocrit in dialysis patients improves brain function. Am J Kidney Dis 33:1122–1130

    Article  PubMed  CAS  Google Scholar 

  • Pourtois G, Schwartz S, Seghier ML, Lazeyras F, Vuilleumier P (2006) Neural systems for orienting attention to the location of threat signals: an event-related fMRI study. Neuroimage 31:920–933

    Article  PubMed  Google Scholar 

  • Preiss M, Kucerova H, Lukavsky J, Stepankova H, Sos P, Kawaciukova R (2009) Cognitive deficits in the euthymic phase of unipolar depression. Psychiatry Res 169:235–239

    Article  PubMed  Google Scholar 

  • Ransome MI, Turnley AM (2007) Systemically delivered erythropoietin transiently enhances adult hippocampal neurogenesis. J Neurochem 102:1953–1965

    Article  PubMed  CAS  Google Scholar 

  • Reppermund S, Zihl J, Lucae S, Horstmann S, Kloiber S, Holsboer F et al (2007) Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation. Biol Psychiatry 62:400–406

    Article  PubMed  CAS  Google Scholar 

  • Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M et al (1998) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A 95:4635–4640

    Article  PubMed  CAS  Google Scholar 

  • Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S et al (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:805–809

    Article  PubMed  CAS  Google Scholar 

  • Sargin D, Hassouna I, Sperling S, Siren AL, Ehrenreich H (2009) Uncoupling of neurodegeneration and gliosis in a murine model of juvenile cortical lesion. Glia 57:693–702

    Article  PubMed  Google Scholar 

  • Sargin D, Friedrichs H, El-Kordi A, Ehrenreich H (2010) Erythropoietin as neuroprotective and neuroregenerative treatment strategy: comprehensive overview of 12 years of preclinical and clinical research. Best Pract Res Clin Anaesthesiol 24:573–594

    Article  PubMed  CAS  Google Scholar 

  • Sargin D, El-Kordi A, Agarwal A, Muller M, Wojcik SM, Hassouna I et al (2011) Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice. BMC Biol 9:27

    Article  PubMed  CAS  Google Scholar 

  • Sattler MB, Merkler D, Maier K, Stadelmann C, Ehrenreich H, Bahr M et al (2004) Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis. Cell Death Differ 11(Suppl 2):S181–S192

    Article  PubMed  Google Scholar 

  • Sinclair LI, Christmas DM, Hood SD, Potokar JP, Robertson A, Isaac A et al (2009) Antidepressant-induced jitteriness/anxiety syndrome: systematic review. Br J Psychiatry 194:483–490

    Article  PubMed  Google Scholar 

  • Siren AL, Radyushkin K, Boretius S, Kammer D, Riechers CC, Natt O et al (2006) Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin. Brain 129:480–489

    Article  PubMed  Google Scholar 

  • Siren AL, Fasshauer T, Bartels C, Ehrenreich H (2009) Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system. Neurotherapeutics 6:108–127

    Article  PubMed  CAS  Google Scholar 

  • Smith DJ, Muir WJ, Blackwood DH (2006) Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder. Bipolar Disord 8:40–46

    Article  PubMed  Google Scholar 

  • Stratton LO, Gibson CA, Kolar KG, Kastin AJ (1976) Neonatal treatment with TRH affects development, learning, and emotionality in the rat. Pharmacol Biochem Behav 5:65–67

    Article  PubMed  CAS  Google Scholar 

  • Viviani B, Bartesaghi S, Corsini E, Villa P, Ghezzi P, Garau A et al (2005) Erythropoietin protects primary hippocampal neurons increasing the expression of brain-derived neurotrophic factor. J Neurochem 93:412–421

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Zhang Z, Wang Y, Zhang R, Chopp M (2004) Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke 35:1732–1737

    Article  PubMed  CAS  Google Scholar 

  • Weiland-Fiedler P, Erickson K, Waldeck T, Luckenbaugh DA, Pike D, Bonne O et al (2004) Evidence for continuing neuropsychological impairments in depression. J Affect Disord 82:253–258

    Article  PubMed  Google Scholar 

  • Wustenberg T, Begemann M, Bartels C, Gefeller O, Stawicki S, Hinze-Selch D et al (2011) Recombinant human erythropoietin delays loss of gray matter in chronic schizophrenia. Mol Psychiatry 16(26–36):1

    Article  Google Scholar 

  • Yatsiv I, Grigoriadis N, Simeonidou C, Stahel PF, Schmidt OI, Alexandrovitch AG et al (2005) Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury. FASEB J 19:1701–1703

    PubMed  CAS  Google Scholar 

  • Yis U, Kurul SH, Kumral A, Tugyan K, Cilaker S, Yilmaz O et al (2008) Effect of erythropoietin on oxygen-induced brain injury in the newborn rat. Neurosci Lett 448:245–249

    Article  PubMed  CAS  Google Scholar 

  • Yu YP, Xu QQ, Zhang Q, Zhang WP, Zhang LH, Wei EQ (2005) Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia. Neurosci Lett 387:5–10

    Article  PubMed  CAS  Google Scholar 

  • Yun J, Koike H, Ibi D, Toth E, Mizoguchi H, Nitta A et al (2010) Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice: possible involvement of a brain-specific transcription factor Npas4. J Neurochem 114:1840–1851

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Clinic for Affective Disorders, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet 6211, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Kamilla W. Miskowiak, Maj Vinberg & Lars V. Kessing

  2. Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK

    Kamilla W. Miskowiak & Catherine J. Harmer

  3. Max Planck Institute of Experimental Medicine and DFG Research Center for Molecular Physiology of the Brain (CMPB), Göttingen, Germany

    Hannelore Ehrenreich

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  1. Kamilla W. Miskowiak
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  2. Maj Vinberg
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  3. Catherine J. Harmer
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  4. Hannelore Ehrenreich
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  5. Lars V. Kessing
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Correspondence to Kamilla W. Miskowiak.

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Miskowiak, K.W., Vinberg, M., Harmer, C.J. et al. Erythropoietin: a candidate treatment for mood symptoms and memory dysfunction in depression. Psychopharmacology 219, 687–698 (2012). https://doi.org/10.1007/s00213-011-2511-1

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