Psychopharmacology DOI 10.1007/s00213-014-3828-3
ORIGINAL INVESTIGATION
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
Received: 28 July 2014 / Accepted: 19 November 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Rationale This study aimed to test how expectations and anxiety sensitivity influence respiratory and autonomic responses to caffeine. Objectives 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. Methods 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. Results 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. C. A. Pané-Farré (*) : M. G. Alius : A. O. Hamm Department of Physiological and Clinical Psychology/Psychotherapy, University of Greifswald, Franz-Mehring-Str. 47, 17487 Greifswald, Germany e-mail:
[email protected] C. Modeß Department of Clinical Pharmacology, University Medicine Greifswald, Felix-Hausdorff-Str. 3, 17487 Greifswald, Germany K. Methling Department of Biochemistry, University of Greifswald, Felix-Hausdorff-Str. 4, 17487 Greifswald, Germany T. Blumenthal Department of Psychology, Wake Forest University, Box 7778 Reynolda Station, Winston-Salem, NC 27109, USA
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. Conclusions 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. Keywords Autonomic arousal . pCO2 . Balanced placebo design . Interoceptive challenge
Introduction Anxiety sensitivity (AS), a trait factor involving fear of somatic arousal sensations, has been linked to an increased proneness of persons to the anxiogenic effect of caffeine (Telch et al. 1996). Moreover, persons suffering from specific psychopathology (e.g., panic disorder, which is also typically paired with increased AS) also show increased anxiety in response to caffeine consumption (Vilarim et al. 2011). The mechanism by which caffeine induces anxiety in these individuals is not completely understood, although specific functional polymorphisms point to the adenosine system as a potential mediator (Yang et al. 2010). In addition, Masdrakis et al. (2009) proposed that the caffeine-induced increase of central lactate (Dager et al. 1999) could be responsible for the anxiogenic effect of caffeine in the described groups. These authors argue that the lactate, which consequently is metabolized to CO2, could trigger an oversensitive suffocation alarm monitor in the brain stem (Klein 1993) which elicits an alarm
Psychopharmacology
reaction resembling a panic attack. From a different line of research, recent animal studies suggest that the orexin neuropeptide system, which has projections to brain regions involved in the regulation of the arousal component of emotional and stress reactions, is also responsive to caffeine stimulation and leads to an increase in anxiety-related behavior (Johnson et al. 2012). Another promising perspective to understand the anxiety-provoking effect of caffeine in high-AS persons is the hypothesis that the somatic sensations evoked by caffeine might be perceived as an interoceptive threat. High-AS persons show defensive mobilization as indicated by an augmentation of simple protective reflexes/behavior, autonomic arousal, and subjective reports of anxiety when confronted with moderate interoceptive sensations, e.g., by use of respiratory challenge procedures (Alius et al. 2013; Melzig et al. 2008, 2011; Zvolensky and Eifert 2001). Thus, the perception of caffeine-induced arousal sensations might trigger an anxiety response to caffeine particularly when these sensations occur unexpectedly or are stronger than expected. It is known that instructional sets or created expectancies may serve as important moderators for the physiological and subjective responses to interoceptive challenges (MacDonald et al. 2001; Rapee et al. 1986; Telch et al. 2010; van der Molen and van den Hout 1988). In a study by Telch et al. (2011), high- and low-AS participants received single inhalations of room air vs. 35% CO2 while being instructed that CO2 will lead to arousal vs. relaxation. Reported fear and the frequency of panic attacks were greater for high-AS participants in the relaxation instruction condition, for whom physiological arousal elicited by CO2 appeared unexpectedly, than for high-AS participants in the expected arousal condition. No expectation-dependent differences were observed in the low-AS group. The current study was designed to test the effects of expected and unexpected somatic symptoms on the physiological responses, especially the respiratory responses, and anxiety symptom reports in individuals with high and low AS. We chose to apply an expectancy-controlled research design (Lotshaw et al. 1996; Rohsenow and Marlatt 1981) to investigate the effects of expected vs. unexpected caffeine administration. In this design, a drug or inert substance is crossed with coffee (which creates an expectation of arousal sensations) or bitter lemon (which causes no expectation of arousal). Without knowledge of the participant, caffeine (the active drug, at a dose of 4 mg/kg body weight) or no drug was added to either beverage, thus allowing delineation of drug vs. expectancy effects. To assess whether the influence of expectancy and anxiety sensitivity on physiological and subjective responding vary across time post-ingestion, we assessed autonomic arousal, respiratory parameters, and subjective symptom reports at two times, either directly following beverage consumption or at the maximum of caffeine absorption in
habitual low caffeine users1 who consume coffee rarely or not at all. It has been shown that caffeine vs. no caffeine conditions can be discriminated at doses lower than administered in the current study (Eissenberg and Griffiths 1997; Silverman and Griffiths 1992). Based on the previous literature (Flaten and Blumenthal 1999), we expected caffeine to result in subjective and autonomic arousal, as indicated by a blood pressure increase which is typically associated with a heart rate decrease (Benowitz 1990), an increase in skin conductance level (SCL) and minute ventilation, and a drop in expired CO2. In accordance with the study by Telch et al. (2011) and assuming that these arousal sensations are perceived as an interoceptive threat by high- but not low-AS participants, we expected greater defensive mobilization in high-AS participants when arousal sensations were provoked unexpectedly, i.e., caffeine was administered in bitter lemon soda. No such difference was expected for low-AS participants.
Materials and methods Participants University students (N=370) were screened with a German version of the Anxiety Sensitivity Index (ASI; Peterson and Reiss 1992) as well as a German translation of the caffeine consumption questionnaire (Schicatano and Blumenthal 1995). Participants were categorized as low caffeine users if they consumed less than 200 mg caffeine per day from any nutrient source and did not regularly (
