Yasuno Fumihiko, Suhara Tetsuya, Okubo Yoshiro, Sudo Yasuhiko, Inoue Makoto, Ichimiya Tetsuya, Takano Akihiro, Nakayama Kazuhiko, Halldin Christer, Farde Lars
National Institute of Radioloogical Sciences, Chiba, Japan.
Am J Psychiatry. 2004 Jun;161(6):1016-22. doi: 10.1176/appi.ajp.161.6.1016.
Several structural and functional brain imaging studies have pointed to a disturbance of thalamic subnuclei in patients with schizophrenia. The dopamine hypothesis of schizophrenia has, however, not been thoroughly examined in terms of this complex structure, which has connections with most brain regions of central interest in schizophrenia research. The aim of the present study was to examine dopamine D(2) receptor binding in subregions of the thalamus in patients with schizophrenia.
The authors used positron emission tomography and the radioligand [(11)C]FLB457 to examine dopamine D(2) receptor binding in thalamic subregions of 10 drug-naive patients with schizophrenia. Binding potential was calculated by the reference tissue method and used as an index for dopamine D(2) receptor binding. Comparisons were made with 19 healthy subjects. Subregions of interest were defined on individual magnetic resonance images using a percentage-based operational approach. Clinical symptoms were rated by using the Brief Psychiatric Rating Scale (BPRS).
The [(11)C]FLB457 binding potential was lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. At a functional level, there was a significant negative correlation between binding potential and BPRS positive symptom scores.
The subregions with low D(2) receptor binding comprise primarily the dorsomedial nucleus and pulvinar, two important components in circuitries previously suggested in the pathophysiology of schizophrenia. Aberrant dopaminergic neurotransmission in thalamic subregions might be a mechanism underlying positive symptoms in schizophrenia.
多项脑结构和功能成像研究表明,精神分裂症患者存在丘脑亚核功能紊乱。然而,精神分裂症的多巴胺假说尚未在这一复杂结构中得到充分研究,该结构与精神分裂症研究中大多数核心脑区存在联系。本研究旨在检测精神分裂症患者丘脑各亚区的多巴胺D(2)受体结合情况。
作者使用正电子发射断层扫描和放射性配体[(11)C]FLB457检测了10例未服用过药物的精神分裂症患者丘脑亚区的多巴胺D(2)受体结合情况。通过参考组织法计算结合潜能,并将其作为多巴胺D(2)受体结合的指标。与19名健康受试者进行了比较。使用基于百分比的操作方法在个体磁共振图像上定义感兴趣的亚区。使用简明精神病评定量表(BPRS)对临床症状进行评分。
精神分裂症患者丘脑中央内侧和后部亚区的[(11)C]FLB457结合潜能较低。在功能水平上,结合潜能与BPRS阳性症状评分之间存在显著负相关。
多巴胺D(2)受体结合较低的亚区主要包括背内侧核和丘脑枕,这是先前在精神分裂症病理生理学中提出的回路中的两个重要组成部分。丘脑亚区多巴胺能神经传递异常可能是精神分裂症阳性症状的潜在机制之一。