Clinical and Genetic Factors Associated with Resistance to Treatment in Patients with Schizophrenia: A Case-Control Study
Clinical and Genetic Factors Associated with Resistance to Treatment in Patients with Schizophrenia: A Case-Control Study
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DOI：
10.3390/ijms20194753
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Hallit, Souheil
中科院分区：
文献类型：
--
作者：
Hajj, Aline;Obeid, Sahar;Hallit, Souheil
目的：评估影响精神分裂症患者（治疗抵抗患者与治疗应答者）治疗应答的临床和遗传因素。我们还旨在研究当我们考虑两种不同的抵抗分类（阳性和阴性综合征量表，PANSS和简明精神病评定量表，BPRS）时，这些因素是否不同。材料和方法：病例对照研究包括治疗抵抗患者和良好反应者。根据使用BPRS和PANSS确定的难治性精神分裂症标准，将患者分为两组。本研究已获得伦理委员会批准（参考文件：CEHDF 1017; HPC-017-2017），所有患者/法律的代表均提供了书面同意。评估临床因素。使用口腔拭子获得DNA，并使用Lightcycler（R）（Roche）对OPRM 1、COMT、DRD 2和MTHFR基因进行基因分型。结果如下：在我们的研究中，当评估患者的精神病理症状和对治疗的反应时，注意到BPRS和PANSS定义之间的一些差异。多因素分析显示，精神分裂症家族史、大学学历、开始治疗时间、氯丙嗪等效剂量以及COMT基因与耐药有关。此外，COMT SNP存在性别相关差异;具有至少一个Met等位基因的男性比瓦尔/瓦尔患者更容易对治疗产生耐药性。结论：揭示与治疗抵抗相关的临床和遗传因素可以帮助我们在个性化医疗的概念中更好地治疗精神分裂症患者。
Objectives: To assess clinical and genetic factors affecting response to treatment in a sample of patients with schizophrenia (treatment-resistant patients versus treatment responders). We also aimed at examining if these factors are different when we consider two different resistance classifications (the positive and negative syndrome scale, PANSS and the brief psychiatric rating scale, BPRS). Material and Methods: A case-control study included treatment-resistant patients and good responders. Patients were stratified in two groups based on the established criteria for treatment-resistant schizophrenia using BPRS and PANSS. The study was approved by the ethical committees (references: CEHDF1017; HPC-017-2017) and all patients/legal representatives gave their written consent. Clinical factors were assessed. DNA was obtained using a buccal swab and genotyping for OPRM1, COMT, DRD2 et MTHFR genes using the Lightcycler((R)) (Roche). Results: Some discrepancies between the BPRS and PANSS definitions were noted in our study when assessing the patients' psychopathological symptoms and response to treatment. The multivariable analysis, taking the presence versus absence of treatment resistance as the dependent variable, showed that that family history of schizophrenia, university studies, time since the beginning of treatment and chlorpromazine equivalent dose as well as the COMT gene are associated with resistance to treatment. In addition, a gender-related difference was noted for COMT SNP; men with at least one Met allele were more prone to be resistant to treatment than Val/Val patients. Conclusion: Uncovering the clinical and genetic factors associated with resistance to treatment could help us better treat our schizophrenic patients in a concept of personalized medicine.