【作者】 刘毅君；

【导师】 李乐华；

【作者基本信息】 中南大学 ， 精神病与精神卫生学， 2008， 硕士

【摘要】 目的:探讨首发精神分裂症患者的5-HT_2C受体基因-759C/T、-697G/C多态性与抗精神病药物治疗反应的关系,试图深化药物作用机制的研究,为新药开发、个体化用药及疾病发病机理的研究提供有益的证据。方法:以自编量表调查179例首发精神分裂症患者的一般临床资料。氯氮平或利培酮治疗8周,以阳性与阴性症状量表（PANSS）评定患者的症状严重程度,并根据量表的减分率将患者分为有效和无效两组（≥50%为有效,＜50%为无效）,以聚合酶链式反应（PCR）扩增及限制性片段长度多态性（RFLP）技术,检测5-HT_2C受体基因-759C/T及-697G/C多态性的基因型和等位基因频率,将所得资料进行x²检验和t检验。结果:1.5-HT_2C受体基因-759C/T多态性野生基因型（C/C）与突变基因型（C/T、T/T）和等位基因C、T的频率在利培酮总疗效有效组和无效组之间有显著性差异（女性患者）,在利培酮改善阴性症状有效组和无效组之间各基因型频率有显著性差异,其等位基因频率无显著性差异。2.5-HT_2C受体基因-697G/C多态性野生基因（C/C）型与突变基因型（C/G、G/G）基因型的频率在利培酮总疗效有效组和无效组之间无显著性差异,其等位基因频率在这两组间有显著差异（女性患者）,在改善阴性症状有效组和无效组之间各基因型和等位基因频率均无显著性差异。3.5-HT_2C受体基因-759C/T多态性各基因型和等位基因的频率在氯氮平总疗效有效组和无效组之间无显著性差异,在氯氮平改善阴性症状有效组和无效组之间各基因型频率有显著性差异（女性患者）,其等位基因频率无显著性差异。4.5-HT_2C受体基因-697G/C多态性各基因型和等位基因的频率在氯氮平总疗效有效组和无效组之间无显著性差异;在氯氮平改善阴性症状有效组和无效组之间各基因型频率无显著性差异,其等位基因频率有显著性差异。5.5-HT_2C受体基因-759C/T多态性、-697G/C多态性的基因型和等位基因频率在利培酮和氯氮平改善阳性症状方面,有效组和无效组之间无显著性差异。6.在抗精神病药物治疗总疗效、阳性及阴性症状改善有效组和无效组之间性别以及家族史无显著性差异。结论:1.5-HT_2C受体基因-759C/T及-697G/C多态性可能与非典型抗精神病药治疗首发精神分裂症的临床疗效有关,C/C基因型和等位基因C可能是总体疗效好和阴性症状疗效好的预测因子。2.性别以及家族史可能与非典型抗精神病药物疗效无关。更多还原

【Abstract】 Objective:To investigate the association of the 5-HT_2Creceptor gene-759C/T and-697C/G polymorphism with therapeutic response to antipsychotics in first-episode schizophrenic patients,attempt to broaden the field of medicine research and provide beneficial evidence for the exploration of novel antipsychotics,individualized therapy and etiopathogenesis of schizophrenia.Methods:179 first-episode schizophrenic patients were investigated with the self-compiled inventories and had been treated by risperidone and clozapine for 8 weeks.The severity of symptoms and the therapeutic responses to risperidone and clozapine were evaluaded by the positive and negative symptom scale（PANSS）.The patients were divided into two groups according to the reductive rate of score of PANSS≥50%and＜50%respectively.The genotypes and allele frequencies of 5-HT_2C receptor genes were assayed by polymerase chain reaction（PCR） amplification and Restriction Fragment Length Polymorphism（RFLP） technique.The data analysis used with x² test and t test.Results:1.The frequencies of C/C genotype of the 5-HT_2Creceptor gene -759C/T polymorphism was significant difference with C/T genotype and T/T genotype between response and non-response to risperidone group in total clinical efficacy（female gender）.There were significant difference of C/C,T/T,T/C genotypes frequencies between response and non-response to negative symptom with risperidone therapy.And no significant difference of T,C allele frequencies was found between the two groups.2.The C/C genotype frequency of the 5-HT_2Creceptor gene -697G/C polymorphism was not significantly different from C/G genotype and G/G genotype between response and non-response to risperidone group in total clinical efficacy.There was significant difference of G,C allele frequencies between the two groups（female gender）.No significant difference of C/C,C/G,G/G genotypes and G,C allele frequencies was found between response and non-response to negative symptom with risperidone therapy.3.No significant difference of C/C,C/T,T/Tgenotypes and T,C allele frequencies of the 5-HT_2Creceptor gene -759C/T polymorphism was found between response to clozapine group and non-response to clozapine group of total clinical efficacy.The frequencies of C/C genotype of the 5-HT_2Creceptor gene -759C/T polymorphism was significant difference with C/T genotype and T/T genotype between negative symptom response to clozapine group and negative symptom non-response to clozapine group（female gender）.No significant difference of T,C allele frequencies was found between the two groups.4.No significant difference of C/C,C/G,G/Ggenotypes and G,C allele frequencies of the 5-HT_2Creceptor gene -697G/C polymorphism was found between response to clozapine group and non-response to clozapine group of total clinical efficacy.There was significant difference of G,C allele frequencies between negative symptom response to clozapine group and negative symptom non-response to clozapine group.No significant difference of C/C,G/G genotypes frequencies was found between the two groups.5.Genotypes and allele frequencies of 5-HT_2Creceptor gene -759C/T and -697G/C polymorphism were not significantly different between response and non-response in positive symptom group.6.We did not find significant difference between response group and non-response group in Gender and family history.Conclusions:1.5-HT_2Creceptor gene -759C/T and -697G/C polymorphism may associate with clinical response to antipsychotics on first-episode schizophrenia.C/C genotype and C allele is likely to be a predictive factor to the improvement of total therapeutic effect and negative symptom with treatment of antipsychotics2.Gender and family history may be not associated with therapeutic effect to antipsychotics更多还原