Erythropoietin for Cognitive Deficits Associated with Schizophrenia, Bipolar Disorder, and Major Depression: A Systematic Review

Xian-Bin Li; Wei Zheng; Yu-Ping Ning; Dong-Bin Cai; Xin-Hu Yang; Gabor S. Ungvari; Chee H. Ng; Chuan-Yue Wang; Yu-Tao Xiang

doi:10.1055/s-0043-114670

Pharmacopsychiatry, Inhaltsverzeichnis

Pharmacopsychiatry 2018; 51(03): 100-104
DOI: 10.1055/s-0043-114670

Original Paper

Erythropoietin for Cognitive Deficits Associated with Schizophrenia, Bipolar Disorder, and Major Depression: A Systematic Review

Xian-Bin Li^#

¹The China Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China

,

Wei Zheng^#

²The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China

,

Yu-Ping Ning^#

²The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China

,

Dong-Bin Cai

³Faculty of Traditional Chinese Medicine, the First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China

,

Xin-Hu Yang

²The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China

,

Gabor S. Ungvari

⁴The University of Notre Dame Australia/Marian Centre, Perth, Australia

⁵School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia

,

Chee H. Ng

⁶Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia

,

Chuan-Yue Wang

¹The China Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China

,

Yu-Tao Xiang

⁷Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China

› Institutsangaben

Abstract

Introduction The purpose of this study is to systematically review the efficacy and safety of adjunctive erythropoietin (EPO) in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression based on randomized controlled trials (RCTs).

Methods Two evaluators independently and systematically searched and selected studies, extracted data, and conducted quality assessment.

Results Four RCTs with 144 patients (71 in the EPO group and 73 in the placebo group) met the study entry criteria. Adjunctive EPO could improve schizophrenia-related cognitive performance. In patients with bipolar disorder, EPO could also enhance sustained attention, recognition of happy faces, and speed of complex information processing across learning, attention, and executive function when compared with placebo. In addition, EPO could enhance verbal recall, recognition, and memory in patients with major depression.

Discussion This preliminary study found that adjunctive EPO appears to be effective in treating cognitive deficits associated with schizophrenia, bipolar disorder, and major depression without major adverse effects observed. Further higher quality RCTs with larger samples are needed to confirm the findings.

Review registration: CRD42017058094

Key words

erythropoietin - cognitive function - schizophrenia - bipolar disorder - major depression

Volltext

Referenzen

References
1 Aas M, Dazzan P, Fisher HL. et al. Childhood trauma and cognitive function in first-episode affective and non-affective psychosis. Schizophr Res. 2011; 129: 12-19
2 Shannon C, Douse K, McCusker C. et al. The association between childhood trauma and memory functioning in schizophrenia. Schizophr Bull. 2011; 37: 531-537
3 Miskowiak KW, Ehrenreich H, Christensen EM. et al. Recombinant human erythropoietin to target cognitive dysfunction in bipolar disorder: A double-blind, randomized, placebo-controlled phase 2 trial. J Clin Psychiatry. 2014; 75: 1347-1355
4 Aas M, Dazzan P, Mondelli V. et al. A systematic review of cognitive function in first-episode psychosis, including a discussion on childhood trauma, stress, and inflammation. Front Psychiatry 2014; 4: 182
5 Zhang XY, Chen da C, Xiu MH. et al. Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls. Hum Genet. 2012; 131: 1187-1195
6 Vieta E. The influence of medications on neurocognition in bipolar disorder. Acta Psychiatr Scand. 2009; 120: 414-415
7 Hill SK, Bishop JR, Palumbo D. et al. Effect of second-generation antipsychotics on cognition: Current issues and future challenges. Expert Rev Neurother 2010; 10: 43-57
8 Reichenberg A, Harvey PD. Neuropsychological impairments in schizophrenia: integration of performance-based and brain imaging findings. Psychol Bull. 2007; 133: 833-858
9 Kastner A, Grube S, El-Kordi A. et al. Common variants of the genes encoding erythropoietin and its receptor modulate cognitive performance in schizophrenia. Mol Med. 2012; 18: 1029-1040
10 Ehrenreich H, Hinze-Selch D, Stawicki S. et al. Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry. 2007; 12: 206-220
11 Miskowiak KW, Favaron E, Hafizi S. et al. Effects of erythropoietin on emotional processing biases in patients with major depression: An exploratory fMRI study. Psychopharmacology (Berl) 2009; 207: 133-142
12 Miskowiak KW, Vinberg M, Christensen EM. et al. Recombinant human erythropoietin for treating treatment-resistant depression: A double-blind, randomized, placebo-controlled phase 2 trial. Neuropsychopharmacology 2014; 39: 1399-1408
13 Wustenberg T, Begemann M, Bartels C. et al. Recombinant human erythropoietin delays loss of gray matter in chronic schizophrenia. Mol Psychiatry. 2011; 16: 26-36
14 Higgins J, Higgins J. eds. Cochrane handbook for systematic reviews of interventions. Chichester: John Wiley & Sons; 2008
15 Miskowiak K, Inkster B, Selvaraj S. et al. Erythropoietin improves mood and modulates the cognitive and neural processing of emotion 3 days post administration. Neuropsychopharmacology 2008; 33: 611-618
16 Miskowiak KW, Vinberg M, Harmer CJ. et al. Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder. Trials 2010; 11: 97
17 Miskowiak KW, Vinberg M, Macoveanu J. et al. Effects of erythropoietin on hippocampal volume and memory in mood disorders. Biol Psychiatry. 2015; 78: 270-277
18 Vinberg M, Miskowiak K, Hoejman P. et al. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: A randomised controlled study. PLoS One 2015; 10: e0127629
19 Miskowiak KW, Macoveanu J, Vinberg M. et al. Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders. Acta Psychiatr Scand. 2016; 134: 249-259
20 Miskowiak KW, Rush Jr. AJ, Gerds TA. et al. Targeting treatments to improve cognitive function in mood disorder: Suggestions from trials using erythropoietin. J Clin Psychiatry. 2016; 77: e1639-e1646
21 Miskowiak KW, Vinberg M, Glerup L. et al. Neural correlates of improved executive function following erythropoietin treatment in mood disorders. Psychol Med. 2016; 46: 1679-1691
22 Ott CV, Vinberg M, Kessing LV. et al. The effect of erythropoietin on cognition in affective disorders – associations with baseline deficits and change in subjective cognitive complaints. Eur Neuropsychopharmacol. 2016; 26: 1264-1273
23 Vinberg M, Weikop P, Olsen NV. et al. Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders: A randomised controlled study. Brain Behav Immun. 2016; 57: 53-57
24 Ehrenreich H, Fischer B, Norra C. et al. Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain 2007; 130: 2577-2588
25 Zheng W, Xiang YQ, Li XB. et al. Adjunctive huperzine A for cognitive deficits in schizophrenia: A systematic review and meta-analysis. Hum Psychopharmacol 2016; 31: 286-295
26 Bora E, Akdede BB, Alptekin K. The relationship between cognitive impairment in schizophrenia and metabolic syndrome: A systematic review and meta-analysis. Psychol Med. 2017; 47: 1030-1040
27 Ehrenreich H, Degner D, Meller J. et al. Erythropoietin: A candidate compound for neuroprotection in schizophrenia, in molecular psychiatry. Mol Psychiatry. 2004; 9: 42-54
28 Bowie CR, Reichenberg A, Patterson TL. et al. Determinants of real-world functional performance in schizophrenia subjects: Correlations with cognition, functional capacity, and symptoms. Am J Psychiatry. 2006; 163: 418-425
29 Zheng W, Li XH, Yang XH et al. Adjunctive memantine for schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials. Psychol Med 2017 [Epub ahead of print]
30 Zheng W, Xiang YQ, Ungvari GS. et al. Huperzine A for treatment of cognitive impairment in major depressive disorder: A systematic review of randomized controlled trials. Shanghai Arch Psychiatry 2016; 28: 64-71
31 Monette MC, Baird A, Jackson DL. A meta-analysis of cognitive functioning in nondemented adults with type 2 diabetes mellitus. Can J Diabetes 2014; 38: 401-408
32 Gorczynski P, Firth J, Stubbs B. et al. Are people with schizophrenia adherent to diabetes medication? A comparative meta-analysis. Psychiatry Res. 2017; 250: 17-24
33 Vancampfort D, Correll CU, Galling B. et al. Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: A systematic review and large scale meta-analysis. World Psychiatry. 2016; 15: 166-174
34 Milev P, Ho BC, Arndt S. et al. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: A longitudinal first-episode study with 7-year follow-up. Am J Psychiatry. 2005; 162: 495-506
35 Xiang YT, Shum D, Chiu HF. et al. Association of demographic characteristics, symptomatology, retrospective and prospective memory, executive functioning and intelligence with social functioning in schizophrenia. Aust N Z J Psychiatry 2010; 44: 1112-1117
36 Addington J, Addington D. Neurocognitive and social functioning in schizophrenia. Schizophr Bull. 1999; 25: 173-182

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