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Sympathetic activity relates to adenosine A2A receptor gene variation in blood-injury phobia

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Variation in the candidate genes adenosine A2A receptor (A2AR), catechol-O-methyl-transferase (COMT), and norepinephrine transporter (NET) has been suggested to influence vulnerability to panic disorder. We therefore investigated patients with another anxiety disorder with an even higher heritability, the blood-injury phobia, for association of these variants and used sympathetic measures during venipuncture, which serve as a naturalistic trigger of anxiety and autonomic hyperarousal, as an intermediate phenotype of anxiety.

Patients homozygous for the A2AR 1976T allele as compared to patients carrying at least one 1976C allele exhibited a significantly increased respiratory rate with a trend towards elevated measures of systolic and diastolic blood pressure and respiratory minute volume. None of the sympathetic measures were influenced by the COMT or NET polymorphisms.

This study provides preliminary data suggesting an influence of the A2AR 1976C/T polymorphism on sympathetic psychophysiological indicators of anxiety-related arousal in blood-injury phobia and thereby further supports a role of the A2AR gene in the pathogenesis of anxiety disorders.

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References

  • Alsene K, Deckert J, Sand P, de Wit H (2003) Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 28:1694–1702

    Article  PubMed  CAS  Google Scholar 

  • Childs E, Hohoff C, Deckert J, Xu K, Badner J, de Wit H (2008) Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 2008 Feb 27 (Epub ahead of print)

  • Deckert J, Nothen MM, Franke P, Delmo C, Fritze J, Knapp M, Maier W, Beckmann H, Propping P (1998) Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease. Mol Psychiatry 3:81–85

    Article  PubMed  CAS  Google Scholar 

  • Domschke K, Freitag CM, Kuhlenbäumer G, Schirmacher A, Sand P, Nyhuis P, Jacob C, Fritze J, Franke P, Rietschel M, Garritsen HS, Fimmers R, Nöthen MM, Lesch KP, Stögbauer F, Deckert J (2004) Association of the functional V158 M catechol-O-methyl-transferase polymorphism with panic disorder in women. Int J Neuropsychopharmacol 7:183–188

    Article  PubMed  CAS  Google Scholar 

  • Domschke K, Braun M, Ohrmann P, Suslow T, Kugel H, Bauer J, Hohoff C, Kersting A, Engelien A, Arolt V, Heindel W, Deckert J (2006) Association of the functional-1019C/G 5-HT 1A polymorphism with prefrontal cortex and amygdala activation measured with 3 T fMRI in panic disorder. Int J Neuropsychopharmacol 9:349–355

    Article  PubMed  CAS  Google Scholar 

  • Ferré S, Ciruela F, Quiroz C, Luján R, Popoli P, Cunha RA, Agnati LF, Fuxe K, Woods AS, Lluis C, Franco R (2007) Adenosine receptor heteromers and their integrative role in striatal function. Scientific World Journal 7:74–85

    PubMed  Google Scholar 

  • Fuxe K, Ferre S, Genedani S, Franco R, Agnati LF (2007) Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function. Physiol Behav 92:210–217

    Article  PubMed  CAS  Google Scholar 

  • Gerlach AL, Spellmeyer G, Vogele C, Huster R, Stevens S, Hetzel G, Deckert J (2006) Blood-injury phobia with and without a history of fainting: disgust sensitivity does not explain the fainting response. Psychosom Med 68:331–339

    Article  PubMed  Google Scholar 

  • Hamilton SP, Slager SL, Heiman GA, Deng Z, Haghighi F, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA (2002) Evidence for a susceptibility locus for panic disorder near the catechol-O-methyltransferase gene on chromosome 22. Biol Psychiatry 51:591–601

    Article  PubMed  CAS  Google Scholar 

  • Hamilton SP, Slager SL, De Leon AB, Heiman GA, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA (2004) Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder. Neuropsychopharmacology 29:558–565

    Article  PubMed  CAS  Google Scholar 

  • Heinz A, Braus DF, Smolka MN, Wrase J, Puls I, Hermann D, Klein S, Grusser SM, Flor H, Schumann G, Mann K, Büchel C (2005) Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 8:20–21

    Article  PubMed  CAS  Google Scholar 

  • Hohoff C, McDonald JM, Baune BT, Cook EH, Deckert J, de Wit H (2005) Interindividual variation in anxiety response to amphetamine: possible role for adenosine A2A receptor gene variants. Am J Med Genet B Neuropsychiatr Genet 139:42–44

    Google Scholar 

  • Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8:858–859

    PubMed  CAS  Google Scholar 

  • Kendler KS, Karkowski LM, Prescott CA (1999) Fears and phobias: reliability and heritability. Psychol Med 29:539–553

    Article  PubMed  CAS  Google Scholar 

  • Kendler KS, Jacobson KC, Myers J, Prescott CA (2002) Sex differences in genetic and environmental risk factors for irrational fears and phobias. Psychol Med 32:209–217

    PubMed  CAS  Google Scholar 

  • Lam P, Hong CJ, Tsai SJ (2005) Association study of A2a adenosine receptor genetic polymorphism in panic disorder. Neurosci Lett 378:98–101

    Article  PubMed  CAS  Google Scholar 

  • Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, Parmentier M (1997) Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2A receptor. Nature 388:674–678

    Article  PubMed  CAS  Google Scholar 

  • Lee YJ, Hohoff C, Domschke K, Sand P, Kuhlenbaumer G, Schirmacher A, Freitag CM, Meyer J, Stöber G, Franke P, Nöthen MM, Fritze J, Fimmers R, Garritsen HS, Stogbauer F, Deckert J (2005) Norepinephrine transporter (NET) promoter and 5′-UTR polymorphisms: association analysis in panic disorder. Neurosci Lett 377:40–43

    Article  PubMed  CAS  Google Scholar 

  • Ohara K, Nagai M, Suzuki Y, Ochiai M, Ohara K (1998) No association between anxiety disorders and catechol-O-methyltransferase polymorphism. Psychiatry Res 80:145–148

    Article  PubMed  CAS  Google Scholar 

  • Rétey JV, Adam M, Honegger E, Khatami R, Luhmann UF, Jung HH, Berger W, Landolt HP (2005) A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci USA 102:15676–15681

    Article  PubMed  Google Scholar 

  • Schmidt B (2005) Methylxanthine therapy for apnea of prematurity: evaluation of treatment benefits and risks at age 5 years in the international caffeine for apnea of prematurity (CAP) trial. Biol Neonate 88:208–213

    Article  PubMed  CAS  Google Scholar 

  • Yamada K, Hattori E, Shimizu M, Sugaya A, Shibuya H, Yoshikawa T (2001) Association studies of the cholecystokinin B receptor and A2a adenosine receptor genes in panic disorder. J Neural Transm 108:837–848

    Article  PubMed  CAS  Google Scholar 

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Hohoff, C., Domschke, K., Schwarte, K. et al. Sympathetic activity relates to adenosine A2A receptor gene variation in blood-injury phobia. J Neural Transm 116, 659–662 (2009). https://doi.org/10.1007/s00702-008-0089-5

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  • DOI: https://doi.org/10.1007/s00702-008-0089-5

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