The 5-HT1A receptor and 5-HT transporter in temporal lobe epilepsy
The 5-HT1A receptor and 5-HT transporter in temporal lobe epilepsy
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DOI：
10.1212/wnl.0b013e31828cf809
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发表时间：
2013-04-01
期刊：
影响因子：
9.9
通讯作者：
Theodore, William H.
中科院分区：
文献类型：
--
作者：
Martinez, Ashley;Finegersh, Andrey;Theodore, William H.
目的：目的：研究颞叶癫痫（TLE）和抑郁症患者的5-HT转运和5-HT 1A受体，方法：对13例患者进行PET检查，用[C-11]DASB检测5-HT转运，用[F-18]FCWAY检测5-HT 1A受体结合，并进行MRI和精神病评定。16名健康志愿者接受了[C-11]DASB，19名接受了[F-18]FCWAY，6名接受了两项PET研究。我们使用参考组织模型来估计[C-11]DASB结合。[F-18]针对无血浆分数校正FCWAY分布容积。将图像归一化到公共空间。主要结果是区域不对称指数。阳性不对称性表明癫痫focus.Results同侧相对减少的结合（反映转运蛋白活性）：平均区域[C-11]DASB结合和不对称性在患者和对照组之间没有差异。[F-18]患者海马、杏仁核和梭状回的FCWAY不对称性显著大于对照组。在以区域作为重复测量的方差分析中，抑郁症诊断对[C-11]DASB不对称性有显著影响，岛叶皮层的[C-11]DASB不对称性显著较高（梭状回的趋势）。在岛叶皮层，患者有一个显着的相关性[F-18]FCWAY不对称和[C-11]DASB asymmetrical.Conclusions：我们的研究表明，增加[C-11]DASB不对称在颞叶和梭状回，和相对减少的转运活性，在受试者与TLE和抑郁症相比，单独的受试者，这意味着减少再摄取，从而增加突触5-HT的可用性。这一发现可能代表了5-HT 1A受体丢失的代偿机制。改变的多巴胺能机制在TLE和伴随的抑郁症中具有重要作用。
Objective: To study 5-HT transport and 5-HT1A receptors in temporal lobe epilepsy (TLE) and depression.Methods: Thirteen patients had PET with [C-11]DASB for 5-HTT and [F-18]FCWAY for 5-HT1A receptor binding, MRI, and psychiatric assessment. Sixteen healthy volunteers had [C-11]DASB, 19 had [F-18]FCWAY, and 6 had both PET studies. We used a reference tissue model to estimate [C-11]DASB binding. [F-18]FCWAY volume of distribution was corrected for plasma-free fraction. Images were normalized to common space. The main outcome was the regional asymmetry index. Positive asymmetry indicates relative reduced binding (reflecting transporter activity) ipsilateral to epileptic foci.Results: Mean regional [C-11]DASB binding and asymmetry did not differ between patients and controls. [F-18]FCWAY asymmetry was significantly greater for patients than controls in hippocampus, amygdala, and fusiform gyrus. On analysis of variance with region as a repeated measure, depression diagnosis had a significant effect on [C-11]DASB asymmetry, with significantly higher [C-11]DASB asymmetry in insular cortex (trend for fusiform gyrus). In insular cortex, patients had a significant correlation between [F-18]FCWAY asymmetry and [C-11]DASB asymmetry.Conclusions: Our study showed increased [C-11]DASB asymmetry in insula and fusiform gyrus, and relatively reduced transporter activity, in subjects with both TLE and depression, as compared to subjects with TLE alone, implying reduced reuptake and thus increased synaptic 5-HT availability. This finding may represent a compensatory mechanism for 5-HT1A receptor loss. Altered serotonergic mechanisms have an important role in TLE and concomitant depression.