title: Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Muenster, Albert-Schweitzer-Campus 1, Gebaeude A9, 48149 Muenster, Germany. Domschke_K@klinik.uni-wuerzburg.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Benedikt
authors.initials: B
authors.lastname: Klauke
authors.forename: Bernward
authors.initials: B
authors.lastname: Winter
authors.forename: Agnes
authors.initials: A
authors.lastname: Gajewska
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Herrmann
authors.forename: Bodo
authors.initials: B
authors.lastname: Warrings
authors.forename: Andreas
authors.initials: A
authors.lastname: Mühlberger
authors.forename: Katherina
authors.initials: K
authors.lastname: Wosnitza
authors.forename: Andrea
authors.initials: A
authors.lastname: Dlugos
authors.forename: Swantje
authors.initials: S
authors.lastname: Naunin
authors.forename: Kathrin
authors.initials: K
authors.lastname: Nienhaus
authors.forename: Manfred
authors.initials: M
authors.lastname: Fobker
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Paul
authors.initials: P
authors.lastname: Pauli
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
mesh_terms: D000328:Adult; D000339:Affect; D002110:Caffeine / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects*
chemical_list: D009479:Neuropeptides; D043705:Receptor, Adenosine A2A; D018013:Receptors, Neuropeptide; C506531:neuropeptide S, human; D002110:Caffeine