Institute for Cognitive Neuroscience, Biopsychology, Ruhr-University of Bochum, D-44780 Bochum, Germany.
Neuroimage. 2013 May 1;71:1-9. doi: 10.1016/j.neuroimage.2013.01.004. Epub 2013 Jan 11.
The neuropeptide S (NPS) system has been suggested to contribute to the pathogenesis of anxiety. In order to further characterize the cognitive-neurophysiological relevance of neuropeptide S in the etiology of anxiety, the influence of a functional neuropeptide S receptor gene (NPSR1) variant on response inhibition and error monitoring was investigated under consideration of the dimensional phenotype of anxiety sensitivity (AS). In a sample of N=97 healthy probands, event-related potential (ERP) measurement using a modified Flanker task was applied allowing for a distinct neurophysiological examination of processes related to response inhibition (Nogo-N2, Nogo-P3) and error monitoring (Ne/ERN). All subjects were genotyped for the functional NPSR1 A/T (Asn(107)Ile) variant (rs324981) and characterized for anxiety sensitivity using the Anxiety Sensitivity Index (ASI). Carriers of the NPSR1 T allele displayed intensified response inhibition (Nogo-P3) and error monitoring (Ne/ERN), which was in both cases paralleled by the behavioral data. Furthermore, anxiety sensitivity was found to be higher in NPSR1 T allele carriers and to correlate with Nogo-P3 and Ne/ERN. A mediation analysis revealed the ERN to mediate the effect between NPSR1 genotype and anxiety sensitivity. In summary, the more active NPSR1 T allele may confer enhanced response inhibition and increased error monitoring and might drive particularly error monitoring as a neurophysiological endophenotype of anxiety as reflected by increased anxiety sensitivity. These findings further corroborate a major role of the neuropeptide S system in the pathogenesis of anxiety and suggest a potentially beneficial use of therapeutic agents targeting the NPS system in anxiety disorders.
神经肽 S（NPS）系统被认为有助于焦虑症的发病机制。为了进一步描述神经肽 S 在焦虑症发病机制中的认知-神经生理相关性，在考虑焦虑敏感（AS）的维度表型的情况下，研究了一种功能性神经肽 S 受体基因（NPSR1）变体对反应抑制和错误监测的影响。在一个由 N=97 名健康个体组成的样本中，使用改良的 Flanker 任务进行事件相关电位（ERP）测量，从而可以对与反应抑制（Nogo-N2、Nogo-P3）和错误监测（Ne/ERN）相关的过程进行独特的神经生理检查。所有受试者均进行了功能性 NPSR1 A/T（Asn(107)Ile）变体（rs324981）的基因分型，并使用焦虑敏感指数（ASI）对焦虑敏感进行了特征描述。NPSR1 T 等位基因携带者表现出增强的反应抑制（Nogo-P3）和错误监测（Ne/ERN），这两种情况都与行为数据相平行。此外，发现 NPSR1 T 等位基因携带者的焦虑敏感性更高，并且与 Nogo-P3 和 Ne/ERN 相关。中介分析显示 ERN 介导了 NPSR1 基因型与焦虑敏感性之间的效应。总之，更活跃的 NPSR1 T 等位基因可能赋予更强的反应抑制和增加的错误监测能力，并可能通过增加焦虑敏感性作为焦虑的神经生理内表型来驱动特别是错误监测。这些发现进一步证实了神经肽 S 系统在焦虑症发病机制中的主要作用，并表明靶向 NPS 系统的治疗剂在焦虑障碍中具有潜在的有益用途。
