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

利培酮、奥氮平、奎硫平、培螺酮、阿立哌唑等新型抗精神病药物在精神分裂症的治疗中发挥了重要作用。与传统的抗精神病药物相比，这些药物具有显著的临床优势，即较少的副作用，如锥体外系症状、过度镇静和认知功能障碍。相反，它们有更高的风险出现不同的副作用，如糖脂代谢障碍和肥胖。糖脂代谢障碍的患者之间也有很大的个体差异，与临床反应和对其他不良反应的易感性相同。因此，迫切需要弄清这些个体间差异的机制，并开发基于这种机制的个体化药物治疗。在本研究中，我们获得了200例接受抗精神病药物治疗的精神分裂症病例，并仍在增加样本数量，以探索包括基因多态性在内的个体差异与抗精神病药物疗效和/或不良反应的关系。1.携带多巴胺D2受体Taq1a基因的A1携带者较A1非携带者在BPRS评分下降百分率上有显著改善。2.药物引起的催乳素升高和纵向变化存在明显的性别差异。3.血浆中丙螺酮代谢产物浓度ID150326对催乳素水平的影响大于母体化合物丙螺酮。

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.