PET receptor studies on scgizophrenia and extrapyramidal side effects.

精神分裂症和锥体外系副作用的 PET 受体研究。

• 批准号: 07671053
• 负责人: OKUBO Yoshiro
• 金额: $ 1.47万
• 依托单位: Tokyo Medical and Dental University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671053/
• 关键词: PET; Schizophrenia; Dopamine

Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of dopamine D2 receptor (D2R) antagonists. D2R is expressed most highly in the striatum, but recent studies using positron emission topography (PET) have failed to show any change in D2R densities in the striatum of schizophrenics. This raises the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex, has been implicated in control of working memory, and working memory dysfunction is a prominent feature of schizophrenia. We therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, D1R binding was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of negative symptoms (for instance emotional withdrawal), and to poor performance in the Wisconsin Card Sort Test (WCST). We propose that dysfunction of D1R signaling in the PFC may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.

精神分裂症被认为涉及多巴胺受体的激活改变，并且对该假设的支持来自多巴胺D2受体（D2R）拮抗剂的抗精神病作用。D2R在纹状体中表达最高，但最近使用正电子发射地形图（PET）的研究未能显示精神分裂症患者纹状体中D2R密度的任何变化。这增加了其他受体也可能参与的可能性。特别是，多巴胺D1受体（D1R），这是高度表达在前额叶皮层，已涉及控制工作记忆，工作记忆功能障碍是精神分裂症的一个突出特征。因此，我们使用PET检查D1R和D2R在药物初治或未用药的精神分裂症患者的脑中的分布。虽然没有观察到在纹状体相对于对照组的差异，D1R结合减少在前额叶皮层的精神分裂症患者。这种减少与阴性症状的严重程度（例如情绪退缩）以及在威斯康星州卡片分类测试（WCST）中的表现不佳有关。我们认为PFC中D1R信号的功能障碍可能导致精神分裂症的阴性症状和认知缺陷。

项目成果

Okubo, Y., Suhara, T., Kobayashi, K., Terasaki, O., Inoue, O., suzuki, K., Tateno, Y., Toru, M.: "PET studies of D1 and D2 receptors in schizophrenic patients." Eur Neuropsychopharmacol. 6 (suppl 3). 73 (1996)

Okubo, Y.、Suhara, T.、Kobayashi, K.、Terasaki, O.、Inoue, O.、suzuki, K.、Tateno, Y.、Toru, M.：“精神分裂症患者 D1 和 D2 受体的 PET 研究

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Yasuhiro Someya、Yoshiro Okubo、Tetsuo Abe、Kunihiko Asai、Michio Toru：“使用 MRI 对精神分裂症患者的大脑形态进行研究”精神病学 38. 55-61 (1996)。

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Itokawa, M.、Toru, M.、Ito, K.、Tsuga, H.、Kameyama, K.、Haga, T.、Arinami, T.、Hamaguchi, H.：“D2S 和 D2L 多巴胺受体亚型的隔离

Suhara, T., Sudo, Y., Fukuda, H., Okubo, Y., Inoue, O.Suzuki, K.: "Imaging of brain serotonin system." Eur Neuropsychopharmacol. 6 (Suppl 3). 165 (1996)

Suhara, T.、Sudo, Y.、Fukuda, H.、Okubo, Y.、Inoue, O.Suzuki, K.：“大脑血清素系统的成像。”