PET receptor studies on scgizophrenia and extrapyramidal side effects.

精神分裂症被认为与多巴胺受体激活的改变有关，多巴胺D2受体（D2R）拮抗剂的抗精神病作用支持了这一假设。D2R在纹状体中表达最多，但最近使用正电子发射形貌（PET）的研究未能显示精神分裂症患者纹状体中D2R密度有任何变化。这就提出了其他受体也参与其中的可能性。特别是，多巴胺D1受体（D1R）在前额叶皮层高度表达，与工作记忆的控制有关，而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检测了D1R和D2R在未使用药物或未使用药物的精神分裂症患者大脑中的分布。虽然纹状体与对照组相比没有差异，但精神分裂症患者前额叶皮层的D1R结合减少。这种减少与消极症状的严重程度（例如情绪退缩）以及威斯康星卡片分类测试（WCST）的糟糕表现有关。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。

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.