Elevated [18F]fluorodopamine turnover in brain of patients with schizophrenia:: An [18F]fluorodopa/positron emission tomography study
Elevated [18F]fluorodopamine turnover in brain of patients with schizophrenia:: An [18F]fluorodopa/positron emission tomography study
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DOI：
10.1523/jneurosci.0805-07.2007
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发表时间：
2007-07-25
影响因子：
5.3
通讯作者：
Gruender, Gerhard
中科院分区：
文献类型：
--
作者：
Kumakura, Yoshitaka;Cumming, Paul;Gruender, Gerhard
以前的正电子发射断层扫描（PET）左旋多巴类似物的研究显示，与健康的年龄匹配的对照组相比，精神分裂症患者纹状体多巴胺合成的能力适度增加。我们假设，不仅是合成，但也营业额放射性标记的多巴胺在患者中升高。为了验证这一假设，我们重新分析了2小时长的[F-18]氟多巴（FDOPA）/PET记录从8个未经药物治疗的精神分裂症患者和15个健康的年龄匹配的对照组，使用新的方法定量[F-18]氟多巴稳态动力学。纹状体中[F-18]氟多巴胺的催化和消除的分数速率常数升高近两倍，这是迄今报道的精神分裂症患者脑中最大的生化差异。校正[F-18]氟多巴代谢物损失后，患者的尾状核和壳核中固有血脑FDOPA清除率增加了20%，杏仁核和中脑增加了50%。然而，FDOPA及其脱羧代谢产物（V-D）的稳态储存量在精神分裂症组的尾状核和杏仁核中减少了三分之一。因此，[F-18]氟多巴的稳态储存减少发生在未经治疗的患者大脑中加速合成的过程中。阳性和阴性症状量表的阳性评分与杏仁核中V-d的大小呈负相关，表明阳性症状与该结构中FDOPA代谢物的稳态储存受损之间存在关联。
Previous positron emission tomography (PET) studies with levodopa analogs have revealed a modestly increased capacity for dopamine synthesis in the striatum of patients with schizophrenia compared with healthy age-matched control subjects. We hypothesized that not just the synthesis but also the turnover of radiolabeled dopamine is elevated in patients. To test the hypothesis, we reanalyzed 2-h-long [F-18]fluorodopa (FDOPA)/PET recordings from eight unmedicated patients with schizophrenia and 15 healthy age-matched control subjects, using new methods for the quantification of [F-18]fluorodopamine steady-state kinetics. The fractional rate constant for the catabolism and elimination of [F-18]fluorodopamine was elevated nearly twofold in striatum, the largest biochemical difference in brain of schizophrenics yet reported. The magnitude of the intrinsic blood-brain FDOPA clearance with correction for this loss of [F-18]fluorodopamine metabolites was increased by 20% in caudate and putamen and by 50% in amygdala and midbrain of the patients. However, the magnitude of the steady-state storage of FDOPA and its decarboxylated metabolites (V-d) was reduced by one-third in the caudate nucleus and amygdala of the schizophrenic group. Thus, reduced steady-state storage of [F-18]fluorodopamine occurs in the midst of accelerated synthesis in brain of untreated patients. Positive scores of the positive and negative syndrome scale correlated inversely with the magnitude of V-d in amygdala, suggesting an association between positive symptoms and impaired steady-state storage of FDOPA metabolites in that structure.