Tourette syndrome (TS) is thought to involve dopaminergic disturbances, but the nature of those disturbances remains controversial. Existing hypotheses suggest that TS involves 1) supersensitive dopamine receptors, 2) overactive dopamine transporters that cause low tonic but high phasic dopamine, 3) presynaptic dysfunction in dopamine neurons, or 4) dopaminergic hyperinnervation. We review evidence that contradicts the first two hypotheses; we also note that the last two hypotheses have traditionally been considered too narrowly, explaining only small subsets of findings. We review all studies that have used positron emission tomography and single-photon emission computerized tomography to investigate the dopaminergic system in TS. The seemingly diverse findings from those studies have typically been interpreted as pointing to distinct mechanisms, as evidenced by the various hypotheses concerning the nature of dopaminergic disturbances in TS. We show, however, that the hyperinnervation hypothesis provides a simple, parsimonious explanation for all such seemingly diverse findings. Dopaminergic hyperinnervation likely causes increased tonic and phasic dopamine. We have previously shown, using a computational model of the role of dopamine in basal ganglia, that increased tonic dopamine and increased phasic dopamine likely increase the propensities to express and learn tics, respectively. There is therefore a plausible mechanistic link between dopaminergic hyperinnervation and TS via increased tonic and phasic dopamine. To further bolster this argument, we review evidence showing that all medications that are effective for TS reduce signaling by tonic dopamine, phasic dopamine, or both.

中文翻译：

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图雷特综合征中的多巴胺能紊乱：综合说明

Tourette 综合征 (TS) 被认为与多巴胺能障碍有关，但这些障碍的性质仍存在争议。现有假设表明 TS 涉及 1) 超敏感的多巴胺受体，2) 过度活跃的多巴胺转运蛋白，导致低张力但高相位多巴胺，3) 多巴胺神经元的突触前功能障碍，或 4) 多巴胺能神经过度支配。我们回顾了与前两个假设相矛盾的证据；我们还注意到最后两个假设传统上被认为过于狭隘，只解释了一小部分发现。我们回顾了所有使用正电子发射断层扫描和单光子发射计算机断层扫描来研究 TS 中的多巴胺能系统的研究。这些研究看似不同的发现通常被解释为指向不同的机制，正如关于 TS 中多巴胺能障碍性质的各种假设所证明的那样。然而，我们表明，超神经支配假说为所有这些看似不同的发现提供了一个简单、简洁的解释。多巴胺能神经支配可能导致强直和相位多巴胺增加。我们之前已经表明，使用多巴胺在基底神经节中的作用的计算模型，增加的强直多巴胺和增加的相位多巴胺可能分别增加表达和学习抽动的倾向。因此，多巴胺能神经过度支配和 TS 通过增加的强直和相位多巴胺之间存在一种看似合理的机制联系。为了进一步支持这一论点，我们回顾了证据，表明所有对 TS 有效的药物都会减少强直多巴胺、阶段性多巴胺或两者的信号传导。