title: Effects of ADORA2A gene variation and caffeine on prepulse inhibition: a multi-level risk model of anxiety.
abstract: The complex pathogenesis of anxiety and panic disorder in particular has been suggested to be influenced by genetic factors such as the adenosine A2A receptor gene (ADORA2A) 1976T>C polymorphism (rs5751876) as well as neuropsychological factors such as early information processing deficits. In 114 healthy individuals (males=57, females=57) controlled for anxiety sensitivity (AS), a multi-level risk model of the development of anxiety was applied: Genetic (ADORA2A 1976T>C variant) and biochemical (300 mg of caffeine citrate vs. placebo) factors were hypothesized to influence early information processing as measured by the prepulse inhibition/facilitation paradigm (stimulus onset asynchronies (SOAs) of 60, 120, 240, 480 and 2000ms between prepulses and startle stimuli). A fourfold interaction of genotype, intervention, gender, and SOAs was discerned. Stratification by SOAs revealed that at 120 ms and 240 ms SOAs in the caffeine condition, PPI was impaired in female ADORA2A 1976TT risk genotype carriers as compared to male ADORA2A 1976TT homozygotes, while no significant effects were observed in the ADORA2A 1976CC/CT non-risk genotype or placebo group. Only in high anxiety sensitive probands, a significant intervention effect was discerned with impaired prepulse facilitation (PPF) due to caffeine. The present results point to an impaired ability to selectively process very early information and to gate irrelevant sensory information, respectively, in female ADORA2A 1976TT homozygotes in response to caffeine, providing further evidence for the adenosinergic system to be involved in the pathogenesis of anxiety.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, D-97080 Wuerzburg, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gajewska
authors.forename: Terry D
authors.initials: TD
authors.lastname: Blumenthal
authors.forename: Bernward
authors.initials: B
authors.lastname: Winter
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Herrmann
authors.forename: Annette
authors.initials: A
authors.lastname: Conzelmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Mühlberger
authors.forename: Bodo
authors.initials: B
authors.lastname: Warrings
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Paul
authors.initials: P
authors.lastname: Pauli
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
mesh_terms: D000328:Adult; D001007:Anxiety / Q000235:genetics* / Q000523:psychology; D002110:Caffeine / Q000494:pharmacology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics; D055139:Sensory Gating / Q000187:drug effects* / Q000235:genetics*; D012737:Sex Factors
chemical_list: D043705:Receptor, Adenosine A2A; D002110:Caffeine