奥氮平治疗早发精神分裂症的疗效与血药浓度及5-HTR2A、DRD2、COMT基因多态性的关联研究

早发精神分裂症（early-onset schizophrenia, EOS）是世界卫生组织确定的年轻人中第三大致残精神障碍，常导致患儿心理发育明显滞后，需要尽早给予个体化的治疗以改善患者预后。既往研究提示功能候选基因多态性、血药浓度都可能影响疗效，而目前国内外尚未见将两者结合在EOS中的疗效研究。本研究拟给予100例汉族EOS患者（17岁以前发病）八周抗精神病药物奥氮平治疗，定期评估患者的精神症状、副反应，并监测血药浓度和相关实验室指标。同时通过TaqMan等位基因分析技术或限制性片段长度多态性等成熟的方法检测检测患者5-HTR2A、DRD2和COMT三个基因8个多态性位点的基因型，从遗传多态性、血药浓度和临床特征全面考察奥氮平疗效的影响因素及其交互作用，阐明影响奥氮平疗效差异的分子遗传学机制，寻找有价值的疗效预测指标并建立疗效预测回归方程，以指导临床个体化治疗方案,提高EOS的治愈率。

Early-onset schizophrenia (EOS) is the World Health Organization ranked psychosis as the third most disabling condition worldwide in youth, and may lead to obvious social dysfunction and interfere seriously with neurodevelopmental processes in a young person, which in turn has the potential to irreversibly alter the trajectory of his or her life. To improve the outcome of the patients of EOS, elaborate and individualized therapeutic regimen is urgently needed. The functional gene polymorphisms and drug (antipsychotics) plasma concentration can both influence the drug response, but few studies explore the contributions of genetic heterogeneity, drug plasma concentration and clinical features of patients to drug response together and interactions of above factors in EOS patients. In this study we will recruit 100 DSM-Ⅴdefined EOS Han patients, older than 7 years old and onset of illness before 17 years old, and all EOS patients will receive a 8-week systematic olanzepine titration treatment and a battery of assessments of treatment effect and safety. Blood olanzepine plasma concentration will be tested regularly and genotyping of 8 polymorphisms of 5-HTR2A, DRD2 and COMT genes will be conducted by Polymerase Chain Reaction （PCR）, Restriction Fragment Length Polymorphism (RFLP) and TaqMan probes genotyping technology. The aim of the study is to explore the predictive factors on olanzepine treatment response in EOS, which can guide the individualized treatment and improve the cure rate of EOS in clinical setting.