Interindividual variation in anxiety response to amphetamine: Possible role for adenosine A<sub>2A</sub> receptor gene variants

Hohoff, Christa; McDonald, J. M.; Baune, Bernhard T.; Cook, Edwin H.; Deckert, Jürgen; Wit, Harriet de

doi:10.1002/ajmg.b.30228

Cited by 50 publications

(42 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both rs5751876 C/T and rs35320474 T/− polymorphisms have been associated with increased anxiety after acute administration of amphetamine in healthy subjects (Hohoff et al 2005). The rs5751876 T/T allele has been associated with panic disorder in Caucasian populations (Deckert et al 1998; Hamilton et al 2004), although this association was not replicated in studies in Japanese (Yamada et al 2001) and Chinese subjects (Lam et al 2005).…”

Section: Genetics and Caffeine Responsementioning

confidence: 99%

Genetics of caffeine consumption and responses to caffeine

2010

Self Cite

View full text Add to dashboard Cite

Rationale Caffeine is widely consumed in foods and beverages and is also used for a variety of medical purposes. Despite its widespread use, relatively little is understood regarding how genetics affects consumption, acute response, or the long-term effects of caffeine. Objective This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers. Results Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of poly-substance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users. Conclusion Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.

show abstract

Section: Genetics and Caffeine Responsementioning

confidence: 99%

Genetics of caffeine consumption and responses to caffeine

2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…The same polymorphism has been linked to panic disorder (PD) (Deckert et al, 1998;Hamilton et al, 2004), suggesting that this variant confers a risk for anxiety states in general. Recently, we have also reported that individuals with the 1976T/T genotype also experience more anxiety after acute doses of the prototypic stimulant drug, D-amphetamine (Hohoff et al, 2005). As the ADORA2A 1976C/T polymorphism is coding but synonymous (Deckert et al, 1996), it has been suggested that the nearly completely linked rs35320474 (2592T/À) polymorphism, 616 bp downstream of the 1976C/T polymorphism, may alter expression of the A 2A receptor (Alsene et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

Childs

Hohoff

Deckert

et al. 2008

Neuropsychopharmacol

Self Cite

216

170

View full text Add to dashboard Cite

Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A 1 and A 2A receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A 2A (ADORA2A) and DRD 2 (DRD2) receptors. Healthy male and female individuals (n ¼ 102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety (Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3 0 -flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.

show abstract

“…Indeed, first molecular genetic studies investigating the impact of ADORA2A gene variation on anxiety after caffeine intervention demonstrated higher self-reported anxiety levels upon caffeine administration dependent on the ADORA2A 1976T risk allele (Alsene et al, 2003;Childs et al, 2008;Rogers et al, 2010). The ADORA2A 1976 genotype has furthermore been shown to drive subjective and objective responses to caffeine during sleep (Retey et al, 2007) as well as to amphetamines (Hohoff et al, 2005; for review see Yang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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

Domschke

Gajewska

Winter

et al. 2011

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Interindividual variation in anxiety response to amphetamine: Possible role for adenosine A_2A receptor gene variants

Cited by 50 publications

References 15 publications

Genetics of caffeine consumption and responses to caffeine

Genetics of caffeine consumption and responses to caffeine

Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

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

Contact Info

Product

Resources

About

Interindividual variation in anxiety response to amphetamine: Possible role for adenosine A2A receptor gene variants

Cited by 50 publications

References 15 publications

Genetics of caffeine consumption and responses to caffeine

Genetics of caffeine consumption and responses to caffeine

Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

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

Contact Info

Product

Resources

About

Interindividual variation in anxiety response to amphetamine: Possible role for adenosine A_2A receptor gene variants