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Studies on the brain neurotransmitters involved in the onset and course of schizophrenia.

对参与精神分裂症发病和病程的大脑神经递质的研究。

基本信息

批准号：
05454310
负责人：
TORU Michio
金额：
$ 3.46万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454310/
关键词：
Schizophrenia Dopamine D2 receptor Dopamine D2 receptor gene S311C variant Negative symptoms アミノ酸ミスセンス変異

项目摘要

This study attempted to examine the heterogeneity of schizophrenia by using a missense variant (S311C) found in the dopamine D2 receptor gene (DRD2). Case-control studies in 156 schizophrenics and 300 controls on an association of a molecular variant of S311C was significantly in schizophrenics (9%) compared with controls (3.7%). Schizophrenics with S311C variant showed less severe negative symptoms than those wihtout. The second association study was dose in expanded numbers of schizophrenics (292) and controls (579). In schizophrenics, significantly higher frequency of those with S311C (8.9%) was again found compared with controls (4.1%). The frequency of S331C in the schizophrenics without negative symptoms (17.1%) was remarkably higher than the controls (p<0.00001). Schizophrenics with S311C were mainly subtyped into paranoid type and a very few into disorganized type. Examination of the courses of the patients by using Bleuler's clssification of the course of schizophrenia revealed that there were significantly fewer cases who showed simple course to deterioration in those with S311C than those without.Thus, these data suggest that the missense variant, S311C,found in DRD2 might not be a risk factor but might be one of the genetic factors which modulate the course of the disease by affecting the response of the patients to antipsychotic drug treatment.The pharmacological properties of receptor proteins with S311C transfected in the cultured cells are now under investigation comparing with those of wild type.

本研究试图通过在多巴胺D2受体基因（DRD2）中发现的错义变体（S311C）来检查精神分裂症的异质性。156名精神分裂症患者和300名对照患者的病例对照研究表明，S311C分子变异的相关性在精神分裂症患者（9%）中显著高于对照组（3.7%）。携带S311C基因变体的精神分裂症患者表现出的阴性症状要比没有S311C基因变体的患者轻。第二项关联研究是扩大精神分裂症患者（292人）和对照组（579人）的剂量。在精神分裂症患者中，与对照组（4.1%）相比，S311C患者的发病频率（8.9%）明显更高。无阴性症状的精神分裂症患者S331C阳性率（17.1%）显著高于对照组（p<0.00001）。患有S311C的精神分裂症患者主要亚型为偏执型，少数亚型为无组织型。用Bleuler的精神分裂症病程分类对患者病程进行检查显示，与没有S311C的患者相比，具有S311C的患者表现出简单病程恶化的病例明显较少。因此，这些数据表明，在DRD2中发现的错义变体S311C可能不是一个危险因素，但可能是通过影响患者对抗精神病药物治疗的反应来调节疾病进程的遗传因素之一。目前正在研究与野生型相比，在培养细胞中转染S311C受体蛋白的药理学特性。