Department of Psychiatry and Psychotherapy, University of Muenster, Albert-Schweitzer-Campus 1, Gebaeude A9, 48149 Muenster, Germany.
Psychopharmacology (Berl). 2012 Aug;222(3):533-41. doi: 10.1007/s00213-012-2678-0. Epub 2012 Mar 8.
RATIONALE/OBJECTIVES: Both the neuropeptide S (NPS) system and antagonism at the adenosine A2A receptor (e.g., by caffeine) were found to play a crucial role in the mediation of arousal and anxiety/panic in animal and human studies. Furthermore, a complex interaction of the neuropeptide S and the adenosinergic system has been suggested with administration of the adenosine A2A receptor antagonist caffeine downregulating NPS levels (Lage et al., 2006) and attenuating the stimulatory effects of NPS in rodents (Boeck et al., 2010).
Thus, in the present study, the impact of the functional neuropeptide S receptor (NPSR) A/T (Asn(107)Ile; rs324981) variant on affect-modulated (neutral, unpleasant, and pleasant IAPS pictures) startle response depending on the administration of 300 mg caffeine citrate was investigated in a sample of 124 (m = 58, f = 66) healthy probands using a double-blind, placebo-controlled design.
ANOVA revealed a significant interaction between NPSR genotype, challenge condition, and picture valence. Comparing startle magnitudes upon stimulation with neutral or emotional pictures between the placebo and caffeine condition, in AA/AT non-risk genotype carriers no significant difference was discerned, while TT risk genotype carriers showed a significantly increased startle magnitude in response to neutral stimuli (p = .02) and a significantly decreased startle magnitude in response to unpleasant stimuli (p = .02) in the caffeine condition as compared to the placebo condition.
In summary, the present findings - extending previous evidence from rodent studies - for the first time provide support for a complex, non-linear interaction of the neuropeptide S and adenosinergic systems affecting the affect-modulated startle response as an intermediate phenotype of anxiety in humans.
背景/目的：在动物和人类研究中，神经肽 S（NPS）系统和腺苷 A2A 受体拮抗剂（例如咖啡因）都被发现对唤醒和焦虑/惊恐的调节起着至关重要的作用。此外，研究表明，神经肽 S 和腺苷能系统之间存在复杂的相互作用，即给予腺苷 A2A 受体拮抗剂咖啡因可下调 NPS 水平（Lage 等人，2006）并减弱 NPS 在啮齿动物中的刺激作用（Boeck 等人，2010）。
因此，在本研究中，采用双盲、安慰剂对照设计，在 124 名（m=58，f=66）健康被试中，根据是否给予 300mg 柠檬酸咖啡因，调查了功能性神经肽 S 受体（NPSR）A/T（Asn(107)Ile；rs324981）变体对受情绪调节（中性、不愉快和愉快 IAPS 图片）的惊吓反应的影响。
方差分析显示，NPSR 基因型、挑战条件和图片效价之间存在显著的相互作用。在安慰剂和咖啡因条件下，比较刺激中性或情绪图片时的惊吓幅度，AA/AT 非风险基因型携带者之间没有明显差异，而 TT 风险基因型携带者在咖啡因条件下，对中性刺激的惊吓幅度显著增加（p=.02），对不愉快刺激的惊吓幅度显著降低（p=.02），而在安慰剂条件下则没有差异。
综上所述，这些发现——扩展了以前来自啮齿动物研究的证据——首次为神经肽 S 和腺苷能系统的复杂、非线性相互作用提供了支持，该相互作用影响人类焦虑的中间表型，即情绪调节的惊吓反应。
