Does fear reactivity during exposure predict panic symptom reduction

Exposure therapy is a core element of behavior therapy for anxiety disorders. Confrontation with feared situations or sensations is thought to facilitate corrective learning by means of acquisition of fear-discordant information. The process of activation of the fear memory/structure, response to the stimulus, and the interpretation of the stimulus and response (Lang, 1971) has been hypothesized as a vital mechanism underlying extinction learning during exposure (e.g., Foa & Kozak, 1986).Specifically, activation is achieved by exposing the individual to cues related to the fear network, and is indexed by physiological (e.g., heart rate accelerations) and experiential (e.g., sensations of heart racing) reactivity that reaches beyond pre-exposure levels. Once activated, the integration of the corrective information/memory, which is incompatible with the components of the fear structure, takes places (Foa & McNally, 1996). Successful integration is indexed by the degree of fear decline during, as well as across, exposure sessions (termed within- and between-session reduction, respectively). Although there are a number of prevailing models on the mechanisms of fear extinction (e.g., Hofmann, 2008; Lissek et al., 2005; for reviews), the basic propositions of fear reactivity (activation and reduction) profoundly influence current clinical practice. Treatment manuals (e.g., Hope, Heimberg, & Turk, 2006, for social anxiety; Foa, Hembree, & Rothbaum, 2007, for PTSD; Antony, Craske, & Barlow, 2006, for specific phobia) often equate fear reactivity during exposure with treatment success (e.g., “These processes, decrease of distress within and between exposure sessions, are thought to indicate that the treatment is succeeding.” (Kozak & Foa, 1997, p. 97). Consequently, therapists should “emphasize the goal of remaining in the situation until her SUDS [subjective units of discomfort distress] decreases by at least 50%”. (Foa, Hembree, & Rothbaum, 2007, p. 72). Graphic displays of successful reactivity patterns are common, “with initial SUDS ratings [Y axis] to be rather high and then to decline over time [X axis].” (Hope et al., 2006, p.106). Given the extensive clinical use of fear reactivity as a predictor of exposure success, one would expect there to be solid empirical evidence testifying to this relation. In a comprehensive review by Craske and colleagues (2008), the authors examined the ability of fear levels during exposure to predict therapeutic outcome. Overall support was weak across studies. For instance, the absence of within-session heart rate decreases during exposures in public-speaking anxious or acrophobic individuals did not result in poorer outcome (Tsao & Craske, 2000; Lang & Craske, 2000; Rachman, Craske, Tallman, & Solyom, 1986), while greater in-session reduction of heart rate in snake-phobic individuals (Rachman, Robinson, & Lopathka, 1987) was even associated with greater return of fear. However, Craske’s (2008) comparison of results across studies was hampered by the studies’ suboptimal methodologies, including lack of, or inadequate, physiological data, poor outcome measures, inadequate exposure situations or materials, or suboptimal timing of process and outcome measures. Given the presumed importance of fear reactivity on the success of exposure treatments, and given the vital need for understanding the mechanisms explaining extinction learning in order to maximize treatment efficacy (Kazdin, 2007; McNally, 2007; Kendall et al., 2009), the primary aim of this study was to examine the predictive value of fear reactivity during repeated in-vivo exposures for patients suffering from panic disorder with agoraphobia. In an effort to improve upon methodological and analytic shortcomings of the prior research (see Craske et al., 2008), the following steps were taken. (1) We assessed indices of fear reactivity across two dimensions (both experiential and physiological), using multiple measures within these dimension. The physiological measures included carbon dioxide (PCO2) and respiration rate (RR), in addition to heart rate (HR). Conceptually, etiological models of panic focus on the role of respiration, specifically CO2, the importance of which has been substantiated by decades of experimental (Smits, Meuret, Zvolensky, Rosenfield, & Seidel, 2009; Dager et al., 1995; Maddock and Carter, 1991; Wilhelm et al., 2001; Blechert, Wilhelm, Meuret, Wilhelm, & Roth, 2010; Gorman et al., 2004; Papp et al., 1995; Meuret & Ritz, 2010 for a review) and clinical research (Meuret, Wilhelm, Ritz, & Roth, 2008, Meuret, Rosenfield, Hofmann, Suvak, & Roth, 2009; Meuret, Rosenfield, Seidel, Bhaskara, & Hofmann, 2010). In a recent ambulatory study, respiratory dysregulation emerged as a prime physiological indicator of impending panic attacks in the hour preceding naturally occurring panic attacks (Meuret, Rosenfield, et al., in press). Notwithstanding, with the exception of a few exposure studies in patients with specific phobias (Wilhelm & Roth, 1998; Alpers, Wilhelm, & Roth, 2005), there are no studies to date examining reactivity of respiration during exposure, either as a process measure or as a predictor of outcome. (2) In addition to measuring multiple indices of the fear network, the setting and duration of the exposures were tailored to best approximate the individual’s fear network. This was done with the intent to maximize the person-specific disconfirmatory process of their fear propositions. As proposed by Craske et al. (2008), exposures should be unrestrained in duration and incorporate a variety of situations (e.g., Marshall, 1985) to evoke a violation (or mismatch) of the expected adverse outcome and lack of occurrence thereof. (3) Reductions in panic disorder severity were assessed weekly during exposure and then two months following treatment termination. This approach allowed sufficient time to evaluate stable change (Shear, Clark, & Feske, 1998), rather than simply looking at temporary changes that may not reflect changes in the underlying fear structure (e.g., Baker et al., 2010). (4) Finally, initial severity and slopes of improvement over time were incorporated into our models, controlling for confounds between activation and initial severity, improving reliability of our outcome measure, and controlling for regression to the mean (Tabachnik & Fidell, 2007). This controls for the possibility that activation relates to improvement simply because it is related to initial severity, which itself is related to improvement in symptoms. Therefore, multilevel, longitudinal growth curve analyses were applied to determine whether experiential and physiological reactivity during exposure predicted slopes of improvement in outcome, as opposed to just predicting outcome at post- or follow-up. Since the slopes are based on multiple data points, they are more accurate and stable than single point outcomes at particular assessment points (e.g., Kraemer & Thiemann, 1989; Rauch et al., 2004) A secondary aim of this study was to investigate whether theoretically distinct coping skills would differentially moderate fear response and reduction in panic disorder severity. This question is vital because exposure treatment is rarely provided in isolation from other treatment techniques (see for review, Meuret, Wolitzky-Taylor, Twohig, & Craske, in press). Moreover, past reports have raised concern about the effects of “arousal-dampening” coping strategies or safety behaviors such as breathing retraining (e.g., Craske, Rowe, Lewin, & Noriega-Dimitri, 1997; Rachman, Radomsky, & Shafran, 2008, for a review). However, empirical evidence for this thesis is surprisingly absent (see Meuret, Wilhelm, Ritz, & Roth, 2003, for a review), in part because proof of concept would require careful assessment and testing of successful skill acquisition (i.e., normalization of CO2) and subsequent application during exposure (i.e., less arousal during exposure; Meuret, Wolitzky-Taylor, et al., in press). The present study investigated the degree to which successful acquisition of respiratory skills was applied during exposure, dampens physiological response, and differentially influences the effect of fear reactivity on outcome. Examining the degree to which coping skills may differentially impact fear response and outcome will aid understanding the factors that contribute to treatment success. Thus, the primary aims of the present investigation are 1) to examine the effect of fear reactivity on overall outcome from treatment for panic disorder, and 2) to determine if these effects differ depending on treatment modality (cognitive training vs. respiratory skills training).