Molecular imaging of altered dopamine transmission in patients with schizophrenia

使用正电子发射断层扫描（PET）和不同的放射性配体，我们的目的是阐明精神分裂症患者多巴胺传递的改变。使用两种不同的放射性配体[^<11>C] NNC 112和[^<11>C] SCH 23390，我们测量了慢性精神分裂症患者和健康对照者的多巴胺D1受体结合。在精神分裂症患者中，两种配体的结合电位在纹状体和皮质区域均显著低于健康对照组。我们使用L-[β-^ C]多巴PET测量了突触前多巴胺的合成<11>，发现精神分裂症患者在左侧尾状核中表现出较高的多巴胺合成，并且丘脑和右侧颞叶皮质中的多巴胺能传递可能与精神分裂症症状的表达有关。最后，我们<11>在精神分裂症患者和健康受试者中使用[^ C] PE 2 I进行PET，以研究多巴胺转运蛋白结合。精神分裂症患者丘脑多巴胺转运体结合率显著高于对照组。多巴胺转运蛋白结合和临床症状评分之间存在显着相关性，表明丘脑中多巴胺转运蛋白结合的改变可能与精神分裂症的病理生理和临床症状有关。

Using positron emission tomography (PET) and different radioligands, we aimed to elucidate altered dopamine transmission in patients with schizophrenia. Using two different radioligands, [^<11>C]NNC112 and [^<11>C]SCH23390, we measured dopamine D1 receptor binding in patients with chronic schizophrenia and healthy controls. In patients with schizophrenia, the binding potentials of both ligands were significantly lower in the striatum and cortical regions than those of healthy controls. We measured presynaptic dopamine synthesis using PET with L-[β-^<11>C]DOPA and found that patients with schizophrenia showed higher dopamine synthesis in the left caudate nucleus, and that dopaminergic transmission in the thalamus and right temporal cortex might be implicated in the expression of symptoms in schizophrenia. Finally, we performed PET using [^<11>C]PE2I in patients with schizophrenia and healthy subjects to investigate dopamine transporter binding. Dopamine transporter binding in the thalamus of patients with schizophrenia was significantly higher than in control subjects. There were significant correlations between dopamine transporter binding and clinical symptom scores suggesting that altered dopamine transporter binding in the thalamus might be related to the pathophysiology and clinical symptoms of schizophrenia.