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精神分裂症患者全血中氯氮平治疗的基因表达分析。

Gene-expression analysis of clozapine treatment in whole blood of patients with psychosis.

作者信息

Harrison Rebecca N S, Murray Robin M, Lee Sang Hyuck, Paya Cano Jose, Dempster David, Curtis Charles J, Dima Danai, Gaughran Fiona, Breen Gerome, de Jong Simone

机构信息

aMRC Social, Genetic & Developmental Psychiatry Centre bDepartment of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London cNIHR BRC for Mental Health, Institute of Psychiatry, Psychology and Neuroscience and SLaM NHS Trust, London, UK.

出版信息

Psychiatr Genet. 2016 Oct;26(5):211-7. doi: 10.1097/YPG.0000000000000140.

Abstract

OBJECTIVES

Clozapine is an atypical antipsychotic primarily prescribed for treatment-resistant schizophrenia. We tested the specific effect of clozapine versus other drug treatments on whole-blood gene expression in a sample of patients with psychosis from the UK.

METHODS

A total of 186 baseline whole-blood samples from individuals receiving treatment for established psychosis were analysed for gene expression on Illumina HumanHT-12.v4 BeadChips. After standard quality-control procedures, 152 samples remained, including 55 from individuals receiving clozapine. In a within-case study design, weighted gene correlation network analysis was used to identify modules of coexpressed genes. The influence of mood stabilizers, lithium carbonate/lithium citrate and sodium valproate was studied to identify their possible roles as confounders.

RESULTS

Individuals receiving clozapine as their only antipsychotic (clozapine monotherapy) had a nominal association with one gene-expression module, whereas no significant change in gene expression was found for other drugs.

CONCLUSION

Overall, this study does not provide evidence that clozapine treatment induces medium to large different gene-expression patterns in human whole blood versus other antipsychotic treatments. This does not rule out the possibility of smaller effects as observed for other common antipsychotic treatments.

摘要

目的

氯氮平是一种非典型抗精神病药物,主要用于治疗难治性精神分裂症。我们在一组来自英国的精神病患者样本中,测试了氯氮平与其他药物治疗对全血基因表达的特定影响。

方法

对186份来自接受已确诊精神病治疗个体的基线全血样本,在Illumina HumanHT-12.v4 BeadChips上进行基因表达分析。经过标准质量控制程序后,剩余152个样本,其中55个来自接受氯氮平治疗的个体。在病例内研究设计中,使用加权基因共表达网络分析来识别共表达基因模块。研究了情绪稳定剂、碳酸锂/柠檬酸锂和丙戊酸钠的影响,以确定它们作为混杂因素的可能作用。

结果

仅接受氯氮平作为抗精神病药物治疗(氯氮平单药治疗)的个体与一个基因表达模块存在名义上的关联,而其他药物未发现基因表达有显著变化。

结论

总体而言,本研究没有提供证据表明氯氮平治疗与其他抗精神病药物治疗相比,会在人类全血中诱导中等至较大的不同基因表达模式。但这并不排除其他常见抗精神病药物治疗所观察到的较小影响的可能性。

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