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The search of the gene polymorphism associated with glycolipid metabolism dysfunction in schizophrenic patients with novel antipsychotics

新型抗精神病药物精神分裂症患者糖脂代谢异常相关基因多态性的寻找

基本信息

批准号：
17591199
负责人：
SOMEYA Toshiyuki
金额：
$ 2.24万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Novel antipsychotics, such as risperidone, olanzapine, quetiapine, perospirone and aripiprazole, have played an important role in the treatment of schizophrenia. These drugs have significant clinical advantages compared to conventional antipsychotics, i.e. lesser side effects such as extrapyramidal symptoms, oversedation and cognitive impairment. On the contrary they have higher risk of different cluster of side effects such as glycolipid metabolism dysfunction and obesity. There are also wide interindividual variations among patients in glycolipid metabolism dysfunction, in the same way as clinical response and susceptibility to other adverse effects. Therefore it is strongly required that the mechanism of these interindividual diversities are cleared up and individualized pharmacotherapy based on the mechanism is developed.In this study, we have obtained 200 schizophrenic cases treated with antipsychotics and are still increasing the number of samples, in order to explore the relationship of interindividual diversity including genetic polymorphisms with response and/or adverse effects against the antipsychotics.So far, we obtained the results such as ;1.A1carrier of dopamine D2 receptor Taq1A gene showed significant higher improvement in % reduction of BPRS score compared to Al non-carriers.2.There was an apparent gender difference in drug-induced prolactin elevation and longitudinal changes.3.A perospirone metabolite concentration in plasma, ID150326, showed a greater impact on prolactin levels than parent compound perospirone did.

新型抗精神病药物利培酮、奥氮平、喹替利、哌罗匹隆、阿立哌唑等在精神分裂症的治疗中发挥了重要作用。与传统抗精神病药物相比，这些药物具有显著的临床优势，即副作用较少，如锥体外系症状，过度镇静和认知障碍。相反，他们有更高的风险，不同集群的副作用，如糖脂代谢功能障碍和肥胖。糖脂代谢功能障碍患者之间也存在广泛的个体差异，与临床反应和对其他不良反应的易感性相同。本研究共收集了200例精神分裂症患者的抗精神病药物治疗资料，并在不断增加样本数，为了探讨包括遗传多态性在内的个体间多样性与反应的关系，或对抗精神病药物的不良反应。到目前为止，我们获得的结果，如; 1.多巴胺D2受体Taq 1A基因携带者A1组BPRS评分下降率显著高于非携带者A1组。诱导催乳素升高和纵向变化。3.血浆中的哌罗匹隆代谢物浓度ID 150326对催乳素水平的影响大于母体化合物哌罗匹隆。