, Volume 232, Issue 11, pp 1931–1939 | Cite as

Anxiety sensitivity and expectation of arousal differentially affect the respiratory response to caffeine

  • Christiane A. Pané-Farré
  • Manuela G. Alius
  • Christiane Modeß
  • Karen Methling
  • Terry Blumenthal
  • Alfons O. Hamm
Original Investigation



This study aimed to test how expectations and anxiety sensitivity influence respiratory and autonomic responses to caffeine.


The current study investigated the effects of expected vs. unexpected caffeine ingestion in a group of persons prone to the anxiety-provoking effect of caffeine (high anxiety sensitive persons, that is, persons scoring at least one SD above the mean on the Anxiety Sensitivity Index (Peterson and Reiss 1992)) as compared to low-anxious controls.


Autonomic arousal (heart rate, skin conductance level), respiratory responding (expired CO2, minute ventilation), and subjective report were assessed in high and low anxiety sensitive participants immediately after beverage consumption and at absorption peak (30 min post-consumption) in four separate sessions during which either coffee (expectation of caffeine) or bitter lemon soda (no expectation of caffeine) was crossed with 4 mg/kg caffeine vs. no drug.


High and low anxiety sensitive persons showed comparable autonomic arousal and symptom reports to caffeine which was modulated by expectation, i.e., greater for coffee. Respiratory responding (CO2 decrease, minute ventilation increase) was more accentuated when caffeine was both expected and administered in the low anxiety sensitive group but more accentuated when caffeine was unexpectedly administered in the high anxiety sensitive group. Autonomic arousal and respiratory effects were observable within a few minutes after caffeine administration and were most pronounced at maximum absorption.


The results highlight the modulating role of expectancies in respiratory responding to caffeine in low vs. high anxiety sensitive persons and might have important implications for the better understanding of unexpected panic attacks.


Autonomic arousal pCO2 Balanced placebo design Interoceptive challenge 


Conflict of interest

This study was supported by the Department of Neuroscience at the University of Greifswald, Germany, and by a W. C. Archie Fund grant from Wake Forest University, USA. The authors declare no conflict of interest.


  1. Alius MG, Pane-Farre CA, Von Leupoldt A, Hamm AO (2013) Induction of dyspnea evokes increased anxiety and maladaptive breathing in individuals with high anxiety sensitivity and suffocation fear. Psychophysiology 50:488–497CrossRefPubMedGoogle Scholar
  2. APA (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, ArlingtonGoogle Scholar
  3. Benowitz NL (1990) Clinical pharmacology of caffeine. Annu Rev Med 41:277–288CrossRefPubMedGoogle Scholar
  4. Bouton ME, Mineka S, Barlow DH (2001) A modern learning theory perspective on the etiology of panic disorder. Psychol Rev 108:4–32CrossRefPubMedGoogle Scholar
  5. Dager SR, Layton ME, Strauss W, Richards TL, Heide A, Friedman SD, Artru AA, Hayes CE, Posse S (1999) Human brain metabolic response to caffeine and the effects of tolerance. Am J Psychiatry 156:229–237PubMedGoogle Scholar
  6. DeMet E, Stein MK, Tran C, Chicz-DeMet A, Sangdahl C, Nelson J (1989) Caffeine taste test for panic disorder: adenosine receptor supersensitivity. Psychiatry Res 30:231–242CrossRefPubMedGoogle Scholar
  7. Eissenberg T, Griffiths RR (1997) Human drug discrimination and multiple chemical sensitivity: caffeine exposure as an experimental model. Environ Health Perspect 105(Suppl 2):509–513CrossRefPubMedCentralPubMedGoogle Scholar
  8. Flaten MA, Blumenthal TD (1999) Caffeine-associated stimuli elicit conditioned responses: an experimental model of the placebo effect. Psychopharmacology (Berl) 145:105–112CrossRefGoogle Scholar
  9. Flaten MA, Aasli O, Blumenthal TD (2003) Expectations and placebo responses to caffeine-associated stimuli. Psychopharmacology (Berl) 169:198–204CrossRefGoogle Scholar
  10. Johnson PL, Samuels BC, Fitz SD, Federici LM, Hammes N, Early MC, Truitt W, Lowry CA, Shekhar A (2012) Orexin 1 receptors are a novel target to modulate panic responses and the panic brain network. Physiol Behav 107:733–742CrossRefPubMedCentralPubMedGoogle Scholar
  11. Klein DF (1993) False suffocation alarms, spontaneous panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry 50:306–317CrossRefPubMedGoogle Scholar
  12. Lotshaw SC, Bradley JR, Brooks LR (1996) Illustrating caffeine’s pharmacological and expectancy effects utilizing a balanced placebo design. J Drug Educ 26:13–24CrossRefPubMedGoogle Scholar
  13. Lykken DT, Venables PH (1971) Direct measurement of skin conductance: a proposal for standardization. Psychophysiology 8:656–672CrossRefPubMedGoogle Scholar
  14. MacDonald AB, Stewart SH, Hutson R, Rhyno E, Loughlin HL (2001) The roles of alcohol and alcohol expectancy in the dampening of responses to hyperventilation among high anxiety sensitive young adults. Addict Behav 26:841–867CrossRefPubMedGoogle Scholar
  15. Masaoka Y, Homma I (2001) The effect of anticipatory anxiety on breathing and metabolism in humans. Respir Physiol 128:171–177CrossRefPubMedGoogle Scholar
  16. Masdrakis VG, Markianos M, Vaidakis N, Papakostas YG, Oulis P (2009) Caffeine challenge and breath-holding duration in patients with panic disorder. Prog Neuropsychopharmacol Biol Psychiatry 33:41–44CrossRefPubMedGoogle Scholar
  17. Melzig CA, Michalowski JM, Holtz K, Hamm AO (2008) Anticipation of interoceptive threat in highly anxiety sensitive persons. Behav Res Ther 46:1126–1134CrossRefPubMedGoogle Scholar
  18. Melzig CA, Holtz K, Michalowski JM, Hamm AO (2011) Interoceptive threat leads to defensive mobilization in highly anxiety sensitive persons. Psychophysiology 48:745–754CrossRefPubMedGoogle Scholar
  19. Mineka S, Hendersen RW (1985) Controllability and predictability in acquired motivation. Annu Rev Psychol 36:495–529CrossRefPubMedGoogle Scholar
  20. Paulus MP, Stein MB (2006) An insular view of anxiety. Biol Psychiatry 60:383–387CrossRefPubMedGoogle Scholar
  21. Peterson RA, Reiss S (1992) Anxiety sensitivity index manual, 2nd edn. International Diagnostic System, WorthingtonGoogle Scholar
  22. Rapee R, Mattick R, Murrell E (1986) Cognitive mediation in the affective component of spontaneous panic attacks. J Behav Ther Exp Psychiatry 17:245–253CrossRefPubMedGoogle Scholar
  23. Rohsenow DJ, Marlatt GA (1981) The balanced placebo design: methodological considerations. Addict Behav 6:107–122CrossRefPubMedGoogle Scholar
  24. Schicatano EJ, Blumenthal TD (1995) The effects of different doses of caffeine on habituation of the human acoustic startle reflex. Pharmacol Biochem Behav 52:231–236CrossRefPubMedGoogle Scholar
  25. Silverman K, Griffiths RR (1992) Low-dose caffeine discrimination and self-reported mood effects in normal volunteers. J Exp Anal Behav 57:91–107CrossRefPubMedCentralPubMedGoogle Scholar
  26. Telch MJ, Silverman A, Schmidt NB (1996) Effects of anxiety sensitivity and perceived control on emotional responding to caffeine challenge. J Anxiety Disord 10:21–35CrossRefGoogle Scholar
  27. Telch MJ, Smits JA, Brown M, Dement M, Powers MB, Lee H, Pai A (2010) Effects of threat context and cardiac sensitivity on fear responding to a 35% CO2 challenge: a test of the context-sensitivity panic vulnerability model. J Behav Ther Exp Psychiatry 41:365–372CrossRefPubMedGoogle Scholar
  28. Telch MJ, Harrington PJ, Smits JA, Powers MB (2011) Unexpected arousal, anxiety sensitivity, and their interaction on CO(2)-induced panic: further evidence for the context-sensitivity vulnerability model. J Anxiety Disord 25:645–653CrossRefPubMedGoogle Scholar
  29. van der Molen GM, van den Hout MA (1988) Expectancy effects on respiration during lactate infusion. Psychosom Med 50:439–443CrossRefPubMedGoogle Scholar
  30. Vilarim MM, Rocha Araujo DM, Nardi AE (2011) Caffeine challenge test and panic disorder: a systematic literature review. Expert Rev Neurother 11:1185–1195CrossRefPubMedGoogle Scholar
  31. Yang A, Palmer AA, de Wit H (2010) Genetics of caffeine consumption and responses to caffeine. Psychopharmacology (Berl) 211:245–257CrossRefGoogle Scholar
  32. Zvolensky MJ, Eifert GH (2001) A review of psychological factors/processes affecting anxious responding during voluntary hyperventilation and inhalations of carbon dioxide-enriched air. Clin Psychol Rev 21:375–400CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Christiane A. Pané-Farré
    • 1
  • Manuela G. Alius
    • 1
  • Christiane Modeß
    • 2
  • Karen Methling
    • 3
  • Terry Blumenthal
    • 4
  • Alfons O. Hamm
    • 1
  1. 1.Department of Physiological and Clinical Psychology/PsychotherapyUniversity of GreifswaldGreifswaldGermany
  2. 2.Department of Clinical PharmacologyUniversity Medicine GreifswaldGreifswaldGermany
  3. 3.Department of BiochemistryUniversity of GreifswaldGreifswaldGermany
  4. 4.Department of PsychologyWake Forest UniversityWinston-SalemUSA

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