Adenosine A2A receptor gene: Evidence for association of risk variants with panic disorder and anxious personality

Hohoff, Christa; Mullings, Emma; Heatherley, Sue V.; Freitag, Christine M.; Neumann, Lisa C.; Domschke, Katharina; Krakowitzky, Petra; Rothermundt, Matthias; Keck, Martin E.; Erhardt, Angelika; Unschuld, Paul G.; Jacob, Christian; Fritze, Jürgen; Bandelow, Borwin; Maier, Wolfgang; Holsboer, Florian; Rogers, Peter J.; Deckert, Jürgen

doi:10.1016/j.jpsychires.2010.02.006

Cited by 90 publications

(60 citation statements)

References 53 publications

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“…The present study extends previous genetic and pharmacological findings of (1) reports of association of the ADORA2A 1976T allele with panic disorder Hamilton et al, 2004;Hohoff et al, 2010) and (2) reports of caffeine exerting an anxiogenic effect (eg, Boulenger et al, 1984;Charney et al, 1985) partially conferred by the ADORA2A 1976TT risk genotype (Alsene et al, 2003;Childs et al, 2008;Rogers et al, 2010) by including emotional stimuli as a third risk factor and by integrating these individual risk factors into a multi-level risk model of anxiety. Also, besides subjective measures of anxiety, in the present study startle reflex potentiation during unpleasant stimuli, which has previously been linked to fearfulness and behavioral inhibition as dimensional phenotypes of anxiety disorders, and therefore has been suggested as a promising intermediate phenotype of anxiety (Cook et al, 1992;Grillon and Baas, 2003;Hawk and Kowmas, 2003;Koch, 1999), was used as an objective outcome measure.…”

Section: Discussionsupporting

confidence: 84%

ADORA2A Gene Variation, Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex

Domschke

Gajewska

Winter

et al. 2011

Neuropsychopharmacol

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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, placebocontrolled 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 ¼ 56, female ¼ 54) stratified for the adenosine A2A receptor (ADORA2A) 1976T4C 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 1976T4C 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.

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Section: Discussionsupporting

confidence: 84%

ADORA2A Gene Variation, Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex

Domschke

Gajewska

Winter

et al. 2011

Neuropsychopharmacol

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“…Thus, there exist genetic associations between adenosine deaminase and deep sleep and between variants in the A 2A receptor and the effects of caffeine on sleep and anxiety (Rétey et al, 2005(Rétey et al, , 2007. Hohoff et al (2010) studied the 1976CϾT polymorphism and other potentially functionally relevant variants in subjects with Parkinson's disease or anxiety traits. The results support an important role of A 2A R variants in the pathogenesis of anxiety disorders, suggesting their use as vulnerability factors for increased susceptibility to these conditions.…”

Section: Receptor Polymorphisms and Disease Susceptibilitymentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

Fredholm¹,

IJzerman²,

Jacobson³

et al. 2011

Pharmacol Rev

1,936

2,797

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“…More recent research has demonstrated that in humans, genetic variation of the adenosine A 2A receptor gene, ADORA2A, mediates an individuals' susceptibility to panic disorder and individual differences in anxiety-related personality, habitual caffeine consumption, and arousal (Cornelis et al 2007;Deckert et al 1998;Hamilton et al 2004;Hohoff et al 2010). Furthermore, individual anxiogenic and sleep-disrupting responses to caffeine have been consistently associated with a common C-to-T substitution at nucleotide 1976 of ADORA2A (Alsene et al 2003;Childs et al 2008;Rétey et al 2007;Rogers et al 2010).…”

Section: Polymorphisms Of Adora2a Modulate the Individual Response Tomentioning

confidence: 99%

Adenosine, Caffeine, and Performance: From Cognitive Neuroscience of Sleep to Sleep Pharmacogenetics

Urry

Landolt

2014

Current Topics in Behavioral Neurosciences

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An intricate interplay between circadian and sleep-wake homeostatic processes regulate cognitive performance on specific tasks, and individual differences in circadian preference and sleep pressure may contribute to individual differences in distinct neurocognitive functions. Attentional performance appears to be particularly sensitive to time of day modulations and the effects of sleep deprivation. Consistent with the notion that the neuromodulator, adenosine adenosine , plays an important role in regulating sleep pressure, pharmacologic and genetic data in animals and humans demonstrate that differences in adenosinergic tone affect sleepiness, arousal and vigilant attention attention in rested and sleep-deprived states. Caffeine Caffeine -the most often consumed stimulant in the world-blocks adenosine receptors and normally attenuates the consequences of sleep deprivation on arousal, vigilance, and attention. Nevertheless, caffeine cannot substitute for sleep, and is virtually ineffective in mitigating the impact of severe sleep loss on higher-order cognitive functions. Thus, the available evidence suggests that adenosinergic mechanisms, in particular adenosine A2A receptor-mediated signal transduction, contribute to waking-induced impairments of attentional processes, whereas additional mechanisms must be involved in higher-order cognitive consequences of sleep deprivation. Future investigations should further clarify the exact types of cognitive processes affected by inappropriate sleep. This research will aid in the quest to better understand the role of different brain systems (e.g., adenosine and adenosine receptors) in regulating sleep, and sleep-related subjective state, and cognitive processes. Furthermore, it will provide more detail on the underlying mechanisms of the detrimental effects of extended wakefulness, as well as lead to the development of effective, evidence-based countermeasures against the health consequences of circadian misalignment and chronic sleep restriction. In press (accepted): January 14, 2014 Addresses for correspondence:Hans-Peter Landolt, Ph.D.

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Adenosine A2A receptor gene: Evidence for association of risk variants with panic disorder and anxious personality

Cited by 90 publications

References 53 publications

ADORA2A Gene Variation, Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex

ADORA2A Gene Variation, Caffeine, and Emotional Processing: A Multi-level Interaction on Startle Reflex

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

Adenosine, Caffeine, and Performance: From Cognitive Neuroscience of Sleep to Sleep Pharmacogenetics

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