Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders
Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders
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DOI：
10.1523/jneurosci.2409-10.2010
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发表时间：
2010-10-27
影响因子：
5.3
通讯作者：
Kasper, Siegfried
中科院分区：
文献类型：
--
作者：
Hahn, Andreas;Lanzenberger, Rupert;Kasper, Siegfried
选择性血清素再摄取抑制剂（SSRIs）是重度抑郁症和焦虑症最常见的治疗选择之一。SSRIs通过阻断血清素转运体，调节血清素能神经传递以及自身受体和异源受体的功能。然而，在网络水平上，治疗引起的变化主要是未知的。因此，我们评估了SSRIs前后血清素- 1a （5-HT1A）自身受体和异受体之间的关系。21例焦虑症患者在艾司西酞普兰治疗12周前后使用[羰基- c -11]WAY-100635进行正电子发射断层扫描；其中15人完成了研究方案。此外，36名未接触药物的健康对照进行了一次测量。5-HT1A受体结合电位（BPND）在中隔背核（DRN）和全脑通过计算参数图量化。DRN自身受体与全脑异源受体5-HT1A BPND之间采用体素线性回归。与先前的观察一致，健康受试者在自身受体和异源受体之间表现出广泛的5-HT1A、BPND正相关。比较艾司西酞普兰治疗前和治疗后的患者，发现杏仁核和海马内自受体-异受体5-HT1A BPND的相关性增强（R-2 = 0.21-0.28 vs 0.49-0.81; p < 0.05-0.001）。相比之下，在几个边缘区域之间，未发现ssri诱导的异受体与异受体5-HT1A BPND相关性的显著变化。这种跨区域的方法表明，治疗诱导的5-HT1A结合在自身受体和异受体之间的关联增强，特别是在与焦虑障碍有关的区域。这些发现提供了关于网络水平治疗效果的补充信息，并确认DRN作为主要调控区域的核心作用。
Selective serotonin reuptake inhibitors (SSRIs) represent one of the most common treatment options in major depression and anxiety disorders. By blocking the serotonin transporter, SSRIs modulate serotonergic neurotransmission as well as the function of autoreceptors and heteroreceptors. However, treatment-induced changes on a network level primarily remain unknown. Thus, we evaluated the association between serotonin-1A (5-HT1A) autoreceptors and heteroreceptors before and after SSRIs. Twenty-one patients with anxiety disorders underwent positron emission tomography using [carbonyl-C-11]WAY-100635 before and after 12 weeks of escitalopram treatment; 15 of them completed the study protocol. Additionally, 36 drug-naive healthy controls were measured once. The 5-HT1A receptor binding potential (BPND) was quantified for the dorsal raphe nucleus (DRN) using a region-of-interest approach and for the entire brain by calculating parametric maps. Voxel-wise linear regression was applied between DRN autoreceptor and whole-brain heteroreceptor 5-HT1A BPND. Consistent with previous observations, healthy subjects showed widespread positive correlations of 5-HT1A, BPND between autoreceptors and heteroreceptors. Comparing patients before versus after escitalopram treatment revealed enhanced associations of autoreceptor-to-heteroreceptor 5-HT1A BPND within the amygdala and hippocampus (R-2 = 0.21-0.28 vs 0.49-0.81; p < 0.05-0.001). In contrast, no significant SSRI-induced changes were found for correlations of heteroreceptor-to-heteroreceptor 5-HT1A BPND between several limbic regions. This interregional approach suggests a treatment-induced reinforcement of the association of 5-HT1A binding between autoreceptors and heteroreceptors specifically in areas involved in anxiety disorders. These findings provide complementary information about treatment effects on a network level and confirm the central role of the DRN as a prime regulatory area.