Zhang Xiong, Gu Xiaoping, Huang Chengchen, Zhang Yue, Shi Yixiang, Qi Dong-Dong
Hulunbuir Mental Health Center, Yakeshi, China.
Shanghai Conlight Medical Institute, Shanghai, China.
Psychiatry Clin Psychopharmacol. 2021 Jun 1;31(2):148-156. doi: 10.5152/pcp.2021.20176. eCollection 2021 Jun.
Schizophrenia is a serious mental illness affecting 0.3-0.7% of the world's population. It is a classic quantitative genetic disease and is affected by a variety of common and rare genetic variants.
To facilitate personalized and precise medicine for schizophrenia treatment, we designed a program by genotyping a panel of related genes for schizophrenic patients using MassARRAY time-of-flight mass spectrometry. The program was 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" categories. Seventy-two of the patients completed the 24-week follow-up observation, during which their PANSS scores were assessed at eight time points.
For all of the subjects who completed the study, the PANSS scores dropped significantly, showing the effectiveness of the treatment. During the 24-week study, PANSS scores of patients whose medications were consistent ( = 48) with their genetic test results dropped from 84.3 (SD = 12.4) to 58.8 (SD = 15.3), and average PANSS change rate reached 56.1% after 24 weeks. In contrast, PANSS scores of patients with genetic tests reported as "Use with caution" or "Use with caution and with frequent blood concentration monitoring" ( = 24) dropped from 81.1 (SD = 10.5) to 63.8 (SD = 10.1), and their average PANSS change rate was 37.6%.
This research indicates that our pharmacogenomic-based program could be a suitable and effective tool to facilitate precise medication in schizophrenia treatment.
精神分裂症是一种严重的精神疾病，影响着全球0.3%-0.7%的人口。它是一种典型的数量遗传疾病，受多种常见和罕见基因变异的影响。
为了促进精神分裂症治疗的个性化和精准化，我们设计了一个程序，通过基质辅助激光解吸电离飞行时间质谱法对一组精神分裂症患者的相关基因进行基因分型。该程序在中国呼伦贝尔心理健康中心进行的一项观察性临床研究中进行了测试。在该研究中，共招募了254名被诊断为精神分裂症的患者并进行基因分型。基因分型结果用于生成报告，列出16种纳入的抗精神病药物的使用建议：“按指示使用”、“谨慎使用”或“谨慎使用并频繁监测血药浓度”类别。72名患者完成了24周的随访观察，在此期间，在8个时间点评估了他们的阳性和阴性症状量表（PANSS）得分。
对于所有完成研究的受试者，PANSS得分显著下降，表明治疗有效。在24周的研究中，药物治疗与基因检测结果一致（n = 48）的患者的PANSS得分从84.3（标准差 = 12.4）降至58.8（标准差 = 15.3），24周后平均PANSS变化率达到56.1%。相比之下，基因检测报告为“谨慎使用”或“谨慎使用并频繁监测血药浓度”（n = 24）的患者的PANSS得分从81.1（标准差 = 10.5）降至63.8（标准差 = 10.1），其平均PANSS变化率为37.6%。
本研究表明，我们基于药物基因组学的程序可能是促进精神分裂症治疗精准用药的合适且有效的工具。
