Journal of Anxiety Disorders 25 (2011) 645–653 Contents lists available at ScienceDirect Journal of Anxiety Disorders Unexpected arousal, anxiety sensitivity, and their interaction on CO 2 -induced panic: Further evidence for the context-sensitivity vulnerability model Michael J. Telch a,∗ , Patrick J. Harrington a , Jasper A.J. Smits b , Mark B. Powers b a Laboratory for the Study of Anxiety Disorders, The University of Texas at Austin, United States b Department of Psychology, Southern Methodist University, United States article info Article history: Received 8 August 2010 Received in revised form 11 February 2011 Accepted 11 February 2011 Keywords: 35% CO2 challenge Panic provocation Context-sensitivity vulnerability model Biological challenge Arousal unexpectedness Anxiety sensitivity abstract The present experiment tested several predictions derived from the context-sensitivity vulnerability model of panic. Participants (N = 79) scoring either high or low in anxiety sensitivity (AS) and with no history of unexpected panic were randomly assigned to one of two instructional sets: expected arousal (EA) or expected relaxation (ER). All participants were administered inhalation of room air and 35% CO 2 in a counterbalanced order. Consistent with theoretical predictions, High-AS participants who received ER instructions showed greater emotional responding compared to High-AS participants who received EA instructions, while instructional set did not affect responding among Low-AS participants. Panic attacks were observed in 52% of the High-AS-ER group compared to 17%, 5%, and 5% in the High-AS-EA, Low-AS- ER, and Low-AS-EA groups respectively. These findings are consistent with the theory’s assertion that dispositional tendencies, such as anxiety sensitivity potentiate the panicogenic effects of threat-relevant context variables. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Laboratory provocation of panic attacks has been widely used as a means for investigating the pathogenesis of panic disorder (Margraf, Ehlers, & Roth, 1986; McNally, 1999). In this paradigm, a panic disorder group and a normal or psychiatric control group are administered an agent that induces somatic perturbations. Demonstration of greater challenge-induced panic among the panic disorder group has been frequently cited as evidence implicating neurobiological dysregulation in the pathogenicity of panic dis- order. Numerous challenge agents have been shown to induce panic attacks in patients with panic disorder but rarely in nor- mal controls. These include sodium lactate (Cowley & Arana, 1990; Liebowitz et al., 1984), yohimbine (Charney, Heninger, & Breier, 1984), carbon dioxide (Griez, deLoof, Pols, Zandbergen, & Lousberg, 1990), caffeine (Charney, Heninger, & Jatlow, 1985), cholecys- tokinin tetrapeptide (Bradwejn, Koszycki & Shriqui, 1991), and hyperventilation (Holt & Andrews, 1989). In contrast to biological explanations (Gorman, Kent, Sullivan, & Coplan, 2000; Klein, 1993), several prominent psychological for- mulations of panic disorder have emerged over the past decade (Barlow, 1988; Beck & Emery, 1985; Bouton, Mineka & Barlow, ∗ Corresponding author at: Department of Psychology, 1 University Station, Mail Code A8000, University of Texas, Austin, TX 78712, United States. Tel.: +1 512 560 4100; fax: +1 702 995 9347. E-mail address: Telch@Austin.utexas.edu (M.J. Telch). 2001; Clark, 1986; Goldstein and Chambless, 1978; McNally, 1990; Wolpe & Rowan, 1988). These converge in positing a core psy- chopathological feature, namely the tendency to respond fearfully to benign somatic cues. The theories diverge, however, in the presumed mechanisms accounting for this tendency i.e., interocep- tive conditioning (Barlow, 1988; Goldstein and Chambless, 1978), catastrophic misinterpretation (Beck & Emery, 1985; Clark, 1986); or an enduring dispositional variable such as anxiety sensitivity (McNally, 1990, 2002; Reiss, 1991). Support for these psychological models comes from studies showing a linkage between the predisposition to perceive anxiety as harmful (i.e., anxiety sensitivity) and panic disorder. Panic disor- der patients show elevations on measures tapping fear of fear, such as the Agoraphobic Cognitions Questionnaire (Chambless, Caputo, Bright & Gallagher, 1984) or the Anxiety Sensitivity Index (ASI) (McNally, 2002; McNally & Lorenz, 1987; Reiss, Peterson, Gursky, & McNally, 1986; Telch, Jacquin, Smits, & Powers, 2003). Anxi- ety sensitivity predicts the diagnostic severity of panic disorder (Jones & Barlow, 1991) and behavioral fear responding to vol- untary hyperventilation predicts agoraphobia status among panic disorder patients (Telch et al., 2003). Moreover, elevated anxiety sensitivity normalizes after successful cognitive-behavioral treat- ment for panic (Smits, Berry, Tart, & Powers, 2008; Smits, Powers, Cho, & Telch, 2004; Telch et al., 1993), as does emotional respond- ing to inhalation of 35% CO 2 gas (Gorman, Martinez, Coplan, Kent, & Kleber, 2004; Schmidt, Lerew, & Jackson, 1997). The aforementioned studies do not rule out the possibility that elevated anxiety sensitivity is a concomitant or consequence of 0887-6185/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.janxdis.2011.02.005