基于药物基因组学的精神分裂症个体化精准用药的有效方法

IF 0.5 4区 医学 Q4 PHARMACOLOGY & PHARMACY Psychiatry and Clinical Psychopharmacology Pub Date : 2020-09-15 DOI:10.21203/rs.3.rs-64915/v1
Yixiang Shi, Xiong Zhang, Xiaoping Gu, Chen-ping Huang, Yue Zhang, Dong-dong Qi
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引用次数: 0

摘要

背景:精神分裂症是一种严重的精神疾病,影响全世界0.3% - 0.7%的人。它是一种典型的数量遗传疾病,受多种常见和罕见的遗传变异的影响。方法:为实现精神分裂症的个体化和精准化治疗,我们设计了一个程序,采用MassArray飞行时间质谱技术对精神分裂症患者的相关基因进行基因分型,包括细胞色素P450基因CYP1A2、CYP2D6、CYP3A4、多巴胺2受体基因(DRD2)、5-羟色胺受体1A和2C基因(HTR1A和HTR2C)以及黑素皮质素4受体(MC4R)基因。结果:该方案在中国呼伦贝尔精神卫生中心进行的一项观察性临床研究中进行了测试。在这项研究中,总共招募了254名被诊断为精神分裂症的患者并进行了基因分型。基因分型结果用于生成报告,列出16种抗精神病药物应放置的位置:“按指导使用”,“谨慎使用”或“谨慎使用并经常进行血浓度监测”栏。然而,无论如何,药物都不会改变。72例患者完成了24周的随访观察,在8个时间点对其PANSS评分进行评估。所有这些人的PANSS评分都显著下降,显示了治疗的有效性。对于那些最初属于“谨慎使用”或“谨慎使用并经常监测血液浓度”类别的队列的治疗,在短期意义上(最多三个月)比那些属于“按指导使用”类别的治疗更有效。然而,从长期来看,仍然是那些最初在“按照指示使用”一栏的人表现更好,他们的PANSS分数下降得更明显。结论:本研究表明,我们基于药物基因组学的项目可能是一种合适和有效的工具,可以促进精神分裂症的精准治疗。
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An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics
Background: Schizophrenia is a serious mental illness affecting 0.3% - 0.7% of people in the whole world. It is a classic quantitative genetic disease and is affected by a variety of common and rare genetic variants. Methods: To facilitate personalized and precise medicine for schizophrenia treatment, we designed a program by genotyping a panel of related genes, including cytochrome P450 genes CYP1A2, CYP2D6, CYP3A4, dopamine 2 receptor gene (DRD2), 5-Hydroxytryptamine Receptor 1A and 2C genes (HTR1A and HTR2C) as well as melanocortin4 receptor (MC4R) gene, for the schizophrenia patients using MassArray time-of-flight mass spectrometry. Results: The program is tested in an observational clinical study conducted at the Hulunbuir Mental Health Center of China. In the study, a total of 254 patients diagnosed with schizophrenia were recruited and genotyped. The genotyping results were used to generate reports listing where the 16 included antipsychotics should be placed: 'Use as directed', 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' columns. However, the medication would not change regardless. 72 of the patients completed the 24-week follow-up observation, during which their PANSS scores were assessed at eight time points. For all of them, the PANSS scores dropped significantly, showing the effectiveness of the treatments. The treatments for those cohorts initially in the 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' categories were more effective than those in the 'Use as directed' category in a shorter term sense, up to three months. However, in the longer term, it was still those who were initially in the 'Use as directed' column fared better, whose PANSS scores dropped more significantly. Conclusions: This research indicated that our pharmacogenomic-based program could be a suitable and effective tool to facilitate precise medicine in schizophrenia treatment.
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来源期刊
Psychiatry and Clinical Psychopharmacology
Psychiatry and Clinical Psychopharmacology Medicine-Psychiatry and Mental Health
CiteScore
1.00
自引率
14.30%
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0
期刊介绍: Psychiatry and Clinical Psychopharmacology aims to reach a national and international audience and will accept submissions from authors worldwide. It gives high priority to original studies of interest to clinicians and scientists in applied and basic neurosciences and related disciplines. Psychiatry and Clinical Psychopharmacology publishes high quality research targeted to specialists, residents and scientists in psychiatry, psychology, neurology, pharmacology, molecular biology, genetics, physiology, neurochemistry, and related sciences.
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