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）神经受体成像的出现促进了阐明神经精神疾病病理生理学的重要策略。由于其临床意义，PET研究首先关注精神分裂症的纹状体多巴胺D2受体，从而对多巴胺假说进行了修正。此外，来自占用测量的经验数据使得直接评估抗精神病药物在人类中的活性成为可能。新放射配体的最新发展为理解精神药物的作用提供了新的视角。利用PET技术，建立神经传递的三维图谱，开发精神药物治疗的新策略。得到了以下结果：1)利用[11C]FLB 457结合的计算机化脑图谱图谱，可以建立活体大脑中腹外D2受体的正常数据库。2)使用[11C]FLB 457，我们发现精神分裂症患者前扣带皮层D2R结合减少，D2R结合与BPRS阳性症状评分呈显著负相关。这些发现表明，颅外区D2R功能的改变可能是精神分裂症阳性症状的基础。3)利培酮对纹状体边缘-皮质区域D2受体的占用与先前报道的相似，与典型抗精神病药物的占用相当。

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.