Neuropeptide-S (NPS) Receptor Genotype Modulates Basolateral Amygdala Responsiveness to Aversive Stimuli
Neuropeptide-S (NPS) Receptor Genotype Modulates Basolateral Amygdala Responsiveness to Aversive Stimuli
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DOI：
10.1038/npp.2011.73
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发表时间：
2011-08-01
影响因子：
7.6
通讯作者：
Domschke, Katharina
中科院分区：
文献类型：
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作者：
Dannlowski, Udo;Kugel, Harald;Domschke, Katharina
最近的研究指出，神经肽-S（neuropeptide-S，NP-S）在焦虑症的病因学中起作用。在动物模型中，杏仁核及其受体（NPSR）被证明在杏仁核中高度表达，杏仁核是恐惧回路的中心结构，也被认为是焦虑症的过度反应。最近，在NPSR基因（rs324981 A/T）的功能多态性已与惊恐障碍和焦虑敏感性。然而，NPSR基因变异在调节恐惧相关杏仁核反应中的作用仍有待澄清。在79名健康受试者的NPSR rs324981基因分型，杏仁核反应的功能磁共振成像进行了评估。参与者在一个强大的情绪处理范式中呈现与恐惧相关的面孔，该范式经常用于研究杏仁核反应。我们观察到一个强大的协会NPSR T-等位基因与右杏仁核反应恐惧相关的面孔。结合峰位于BLA。此外，在这个BLA集群厌恶刺激的反应预测参与者的自我报告的伤害避免，但不是抑郁水平。我们的结论是，NPSR基因型与增加杏仁核反应恐惧相关的刺激。因此，NPSR rs324981显然对焦虑相关性状产生间接影响，并通过形成与恐惧相关的边缘系统活动而潜在地促成焦虑障碍的发病机制。Neuropsychopharmacology（2011）36，1879-1885; doi：10.1038/npp.2011.73; 2011年4月27日在线发表
Recent studies point to a role of neuropeptide-S (NPS) in the etiology of anxiety disorders. In animal models, NPS and its receptor (NPSR) were shown to be highly expressed in the amygdala, a central structure in the fear circuit, also known to be hyper-responsive in anxiety disorders. Recently, a functional polymorphism in the NPSR gene (rs324981 A/T) has been associated with panic disorder and anxiety sensitivity. However, the role of NPSR gene variation in the modulation of fear-related amygdala responsiveness remains to be clarified. In 79 healthy subjects genotyped for NPSR rs324981, amygdala responses were assessed by means of fMRI. The participants were presented with fear-relevant faces in a robust emotion-processing paradigm frequently used to study amygdala responsiveness. We observed a strong association of NPSR T-alleles with right amygdala responsiveness to fear-relevant faces. The association peak was located in the BLA. Furthermore, responsiveness to aversive stimuli within this BLA cluster predicted a participant's self-reported harm avoidance but not depression level. We conclude that NPSR genotype is associated with increased amygdala responsiveness to fear-relevant stimuli. Thereby, NPSR rs324981 apparently causes an indirect effect on anxiety-related traits and potentially contributes to the pathogenesis of anxiety disorders by shaping fear-related limbic activity. Neuropsychopharmacology (2011) 36, 1879-1885; doi:10.1038/npp.2011.73; published online 27 April 2011