Development of three-dimensional atlas of neural transmission and its application for new psychotropic medication

正电子发射断层扫描(PET)神经感受器成像的出现为阐明神经精神障碍的病理生理学提供了一个重要的策略。PET研究首先关注精神分裂症的纹状体多巴胺D2受体，因为它具有临床意义，导致修订了多巴胺假说。此外，来自入住率测量的经验数据使直接评估抗精神病药物在人类身上的活性成为可能。新的放射性配体的最新发展为理解精神药物的行为提供了新的视角。利用正电子发射计算机断层扫描，我们的目标是制作一个三维的神经传递图谱，并致力于开发新的精神药物治疗策略。结果如下：1)[11C]FLB457结合的计算机脑图谱使建立活体人脑纹状体外D2受体的正常数据库成为可能。2)利用[11C]FLB457，我们发现精神分裂症患者的前扣带回D2R结合减少，且D2R结合与BPR阳性症状评分呈显著负相关。这些发现表明，纹状体外区域D2R功能的改变可能是精神分裂症阳性症状的基础。3)利培酮在边缘皮质区域的D2受体占有率与先前关于纹状体的报道相似，与典型的抗精神病药物相似。

The advent of positron emission tomography(PET) neuroreceptor imaging has facilitated an important strategy for elucidating the pathophysiology of neuropsychiatric disorders. PET studies first focused on the striatal dopamine D2 receptor in schizophrenia because of its clinical significance, leading to a revisal of the dopamine hypothesis. Furthermore, empirical data from occupancy measurements have made it possible to directly evaluate the activity of antipsychotic drugs in humans. Recent developments of new radioligands have given rise to new perspectives for understanding actions of psychotroic dugs. Using PET, we aimed to make a three-dimensional atlas of neural transmission and aimed to develop new strategy of psychtropic medication. The follwing results were obtained.1) The use of Computerized Brain Atlas sis of [11C]FLB 457 binding made it possible to build a normal database for the extrastriatal D2 receptors in the living human brain.2) Using [11C]FLB 457, we found reduced D2R binding in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation between D2R binding and the positive symptom score on BPRS. These findings suggest that alterations in D2R function in the extrastriatal region may underlie the positive symptoms of schizophrenia.3) D2 receptor occupancy with risperidone in the limbic-cortical regions was similar to that of previous reports regarding the striatum, and it would be comparable to that of typical antipsychotics.