TY - JOUR
T1 - ADORA2A Gene Variation, Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex
AU - Domschke, Katharina
AU - Gajewska, Agnieszka
AU - Winter, Bernward
AU - Herrmann, Martin J.
AU - Warrings, Bodo
AU - Muehlberger, Andreas
AU - Wosnitza, Katherina
AU - Glotzbach, Evelyn
AU - Conzelmann, Annette
AU - Dlugos, Andrea
AU - Fobker, Manfred
AU - Jacob, Christian
AU - Arolt, Volker
AU - Reif, Andreas
AU - Pauli, Paul
AU - Zwanzger, Peter
AU - Deckert, Juergen
PY - 2012/2
Y1 - 2012/2
N2 - There is converging evidence for genetic, biochemical, and neuropsychological factors to increase the risk for anxiety and anxiety disorders. The pathogenesis of anxiety disorders is assumed to be influenced by a complex interaction of these individual risk factors on several levels, affecting intermediate phenotypes of anxiety such as the startle reflex. Thus, in the present double-blind, placebo-controlled study we attempted to paradigmatically investigate a multi-level pathogenetic model of anxiety by testing the effect of 300?mg caffeine citrate as an antagonist at the adenosine A2A receptor vs placebo on the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) startle reflex in 110 healthy individuals (male=56, female=54) stratified for the adenosine A2A receptor (ADORA2A) 1976T>C polymorphism (rs5751876). In addition to the expected main effect of picture category (highest startle amplitude for unpleasant, lowest for pleasant pictures) groups across all ADORA2A 1976T>C genotype and intervention (caffeine vs placebo) groups, an interaction effect of genotype, intervention, and picture category was discerned: In ADORA2A 1976TT risk genotype carriers, highest startle magnitudes were observed after caffeine administration in response to unpleasant pictures, with this effect arising particularly from the female subgroup. Our data point to a complex, multi-level, and potentially gender-specific pathogenetic model of anxiety, with genetic and biochemical factors interactively increasing the risk of maladaptive emotional processing and thereby possibly also anxiety disorders. The present findings may eventually aid in improving primary and secondary prevention by sharpening the risk profiles of anxiety-prone individuals.
AB - There is converging evidence for genetic, biochemical, and neuropsychological factors to increase the risk for anxiety and anxiety disorders. The pathogenesis of anxiety disorders is assumed to be influenced by a complex interaction of these individual risk factors on several levels, affecting intermediate phenotypes of anxiety such as the startle reflex. Thus, in the present double-blind, placebo-controlled study we attempted to paradigmatically investigate a multi-level pathogenetic model of anxiety by testing the effect of 300?mg caffeine citrate as an antagonist at the adenosine A2A receptor vs placebo on the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) startle reflex in 110 healthy individuals (male=56, female=54) stratified for the adenosine A2A receptor (ADORA2A) 1976T>C polymorphism (rs5751876). In addition to the expected main effect of picture category (highest startle amplitude for unpleasant, lowest for pleasant pictures) groups across all ADORA2A 1976T>C genotype and intervention (caffeine vs placebo) groups, an interaction effect of genotype, intervention, and picture category was discerned: In ADORA2A 1976TT risk genotype carriers, highest startle magnitudes were observed after caffeine administration in response to unpleasant pictures, with this effect arising particularly from the female subgroup. Our data point to a complex, multi-level, and potentially gender-specific pathogenetic model of anxiety, with genetic and biochemical factors interactively increasing the risk of maladaptive emotional processing and thereby possibly also anxiety disorders. The present findings may eventually aid in improving primary and secondary prevention by sharpening the risk profiles of anxiety-prone individuals.
KW - adenosine
KW - caffeine
KW - ADORA2A
KW - panic disorder
KW - emotional processing
KW - startle
U2 - 10.1038/npp.2011.253
DO - 10.1038/npp.2011.253
M3 - Article
C2 - 22012471
SN - 0893-133X
VL - 37
SP - 759
EP - 769
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 3
ER -