Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin
Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin
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DOI：
10.1038/sj.mp.4001907
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发表时间：
2007-02-01
影响因子：
11
通讯作者：
Krampe, H.
中科院分区：
文献类型：
--
作者：
Ehrenreich, H.;Hinze-Selch, D.;Krampe, H.
精神分裂症被越来越多地认为是一种神经发育疾病，具有额外的退行性成分，包括认知能力下降和皮质灰质丧失。我们假设，除了稳定的抗精神病药物外，一种神经保护/神经营养的附加策略-重组人促红细胞生成素(RhEPO)-甚至可能能够改善慢性精神分裂症患者的认知功能。因此，我们设计了一项双盲、安慰剂对照、随机、多中心、原则验证(II期)研究。这项研究的总持续时间为2年，个人持续时间为12周，另外还进行了16周的安全访问。慢性精神分裂症男性(N=39)，有明确的认知缺陷(>；=1S.D.用药和病情稳定的患者，每周短期(15min)静脉滴注4万IU重组人促红细胞生成素(n=20)或安慰剂(n=19)，疗程3个月。主要观察指标为第12周精神分裂症相关认知功能。在基线、2周、4周和12周进行神经心理学测验(RBANS各分测验延迟记忆、语言-语义流利性、注意力和威斯康星卡片分类测验(WCST-)-持久性错误)。安慰剂和重组人促红细胞生成素患者在所有评估类别中都有所改善。接受重组人促红细胞生成素的患者在与精神分裂症相关的认知操作(RBANS分测试，WCST-)方面比安慰剂患者有显著改善，但对精神病理学或社会功能没有影响。此外，重组人促红细胞生成素治疗后，血清中神经胶质损伤标志物S100B的水平显著下降。事实上，重组人促红细胞生成素是第一种对认知产生选择性和持久有益影响的化合物，这一事实应该会鼓励精神分裂症的新治疗策略。
Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>= 1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64)-perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.