Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation

Katharina Domschke*, Benedikt Klauke, Bernward Winter, Agnes Gajewska, Martin J. Herrmann, Bodo Warrings, Andreas Muehlberger, Katherina Wosnitza, Andrea Dlugos, Swantje Naunin, Kathrin Nienhaus, Manfred Fobker, Christian Jacob, Volker Arolt, Paul Pauli, Andreas Reif, Peter Zwanzger, Juergen Deckert

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)533-541
Issue number3
Publication statusPublished - Aug 2012


  • NPS
  • NPSR
  • Caffeine
  • Adenosine 2A receptor
  • Emotion
  • Acoustic startle reflex

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