PET study of dopamine D1 and D2 receptors in epilepsy and epileptic psychosis.

癫痫和癫痫性精神病中多巴胺 D1 和 D2 受体的 PET 研究。

• 批准号: 11670931
• 负责人: OKUBO Yoshiro
• 金额: $ 2.24万
• 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 Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670931/
• 关键词: epilepsy; epileptic psychosis; temporal lobe; dopamine; PET; 精神分裂病; てんかん精神病; MRI

Since the nineteenth century, psychiatrists have been interested in psychotic states in epileptic patients. The characteristics of schizophrenia-like psychosis of epilepsy(SLPE)were reported in the previous clinical description ; (a)schizophrenia-like psychosis is 6-12 times more likely to occur in epileptic patients than in the general population, (b)the onset of psychosis follows some 10-15 years after the onset of the epilepsy, and(c)the risk to occur the psychosis is highest for patients with temporal lobe epilepsy. To study the association between schizophrenia and SLPE, structural and functional neuroimaging techniques are increasingly indispensable. As regards neurochemical abnormalities of psychotic patients with epilepsy, reduced specific binding of Iodine-123 IBZM(dopamine D2 receptor antagonist)to strial D2 receptors have been demonstrated in the psychotic patients compared to those without psychosis. This result support to the "dopamine hypothesis" for schizophrenia. There … More is growing evidence that extrastriatal D2 receptors, in spite of their low density, have pathophysiological significance for schizophrenia. We used the CBA(computerized brain atlas)to explore the extrastriatal distribution of D2 receptors in 13 healthy subjects using[11C]FLB 457, a substituted benzamide with very high affinity for D2 and D3 receptors. The cerebral cortices showed lower levels with significant regional differences. Binding was highest in the temporal cortex and hippocampus followed by the anterior cingulate gyrus, and the parietal and frontal cortices, but was lowest in the occipital cortex. The use of CBA for analysis of[11C]FLB 457 binding makes it possible to build a normal database for the extrastriatal D2 receptors in the living human brain. Further, we aimed to examine the extrastriatal D2 receptors of patients with schizophrenia. Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using[11C]FLB 457. Comparison was made with 18 healthy controls. Region of interest analysis was performed using the reference tissue method and binding potential(BP)was used for the index of dopamine D2 receptor binding. The BP value was significantly lower in the anterior cingulate cortex about 12% in drug naive patients with schizophrenia than in normal controls. Alteration in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia. Finally, we examined a group of SLPE patients and compared them with a group of epileptic patients without psychosis and a normal data base. At the present, we have completed inspective evaluation of[11C]FLB457 PET images and have found no remarkable difference in the distribution of dopamine D2 receptors. Further analysis using sophisticated method such as pixel-by-pixel analysis is need to conclude. Less

自19世纪以来，精神病学家一直对癫痫患者的精神状态感兴趣。精神分裂症样癫痫性精神病（SLPE）的特征在以前的临床描述中有报道；(a)癫痫患者发生精神分裂症样精神病的可能性是一般人群的6-12倍，(b)精神病的发作是在癫痫发作后10-15年左右发生的，(c)颞叶癫痫患者发生精神病的风险最高。为了研究精神分裂症与SLPE之间的关系，结构和功能神经影像学技术越来越不可或缺。关于精神病患者癫痫的神经化学异常，与非精神病患者相比，精神病患者的碘-123 IBZM（多巴胺D2受体拮抗剂）与试验D2受体的特异性结合减少。这一结果支持了精神分裂症的“多巴胺假说”。越来越多的证据表明，尽管D2受体密度低，但它对精神分裂症具有病理生理意义。我们使用[11C]FLB 457（一种对D2和D3受体具有非常高亲和力的取代苯甲酰胺），利用CBA（计算机化脑图谱）探索13名健康受试者的D2受体的纹外分布。大脑皮层水平较低，且区域差异显著。颞叶皮层和海马的结合程度最高，其次是前扣带回、顶叶和额叶皮层，而枕叶皮层的结合程度最低。利用CBA对[11C]FLB 457结合进行分析，可以建立活体大脑中腹外D2受体的正常数据库。此外，我们旨在检查精神分裂症患者的纹外D2受体。本文对11例未用药的男性精神分裂症患者进行了正电子发射断层扫描[11C] flb457。与18名健康对照者进行比较。参照组织法进行兴趣区分析，结合电位（binding potential， BP）作为多巴胺D2受体结合指数。未接受药物治疗的精神分裂症患者的前扣带皮层BP值明显低于正常对照组约12%。纹外区D2受体功能的改变可能是精神分裂症阳性症状的基础。最后，我们检查了一组SLPE患者，并将其与一组无精神病和正常数据库的癫痫患者进行了比较。目前，我们完成了对[11C]FLB457 PET图像的检查性评价，未发现多巴胺D2受体的分布有显著差异。需要使用诸如逐像素分析之类的复杂方法进行进一步分析。少

项目成果

Suhara T, Okubo Y, Sudo Y, Tanada S: "PET research in pathophysiology and treatment of psychiatric illness."Positron Emission Tomography in the Millennium.. 33-40 (2000)

Suhara T、Okubo Y、Sudo Y、Tanada S：“病理生理学和精神疾病治疗中的 PET 研究。”千年正电子发射断层扫描.. 33-40 (2000)

Saijo T, Abe T, Someya Y, Sassa T, Sudo Y, Suhara T, Shuno T, Asai K, Okubo Y: "Ten year progressive ventricular enlargement in schizophrenia : An MRI morphometrical study."Psychiatry and Clinical Neuroscience.. 55. 41-47 (2001)

Saijo T、Abe T、Someya Y、Sassa T、Sudo Y、Suhara T、Shuno T、Asai K、Okubo Y：“精神分裂症十年进行性心室扩大：MRI 形态测量研究。”精神病学和临床神经科学.. 55.

Suhara T, Okubo Y, Yasuno F, Sudo Y, Inoue M, Ichimiya T, Nakashima Y, Nakayama K, Tanada S, Suzuki K, Halldin C, Farde L: "Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia."Arch Gen Psychiatry.. (in press). (2001)

Suhara T、Okubo Y、Yasuno F、Sudo Y、Inoue M、Ichimiya T、Nakashima Y、Nakayama K、Tanada S、Suzuki K、Halldin C、Farde L：“精神分裂症患者前扣带皮层中的多巴胺 D2 受体结合减少。

Hara, K., Terasaki O., Okubo Y.: "Dipole estimation of alpha EEG during alcohol ingestion in males genotypes for ALDH2."Life Sciences. 67. 1163-1173 (2000)

Hara, K.、Terasaki O.、Okubo Y.：“男性 ALDH2 基因型酒精摄入期间 α 脑电图的偶极估计。”生命科学。

Okubo, Y., Suhara T. al.: "Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography."Life Sciences,. 66. 2455-2464 (2000)

Okubo, Y., Suhara T. al.：“通过正电子发射断层扫描研究精神分裂症患者的血清素 5-HT2 受体。”生命科学，。