The interaction of nicotine withdrawal and panic disorder in the prediction of panic-relevant responding to a biological challenge.

Smoking rates have remained relatively stable in recent years (CDC, 2011). Some scholars have suggested that the stable rates of smoking may be at least partially explained by characteristics of 'todays' smokers, including those with mental disorders (Kalman, Morissette, & George, 2005; Lasser et al., 2000). Although smoking has historically been studied in relation to many co-occurring psychopathological conditions (e.g., schizophrenia, depressive disorders), comparatively less scholarly attention has been focused on anxiety and its disorders (Ziedonis et al., 2008). Yet, a growing corpus of work indicates that rates of smoking are higher among those with anxiety disorders relative to many other psychiatric conditions as well as those with no psychiatric illness (McCabe et al., 2004). Some of the most robust relations thus far documented between smoking and anxiety disorders have been evident for panic psychopathology (Zvolensky, Feldner, Leen-Feldner, & McLeish, 2005). For example, epidemiological (Farrell et al., 2001), community (Hayward, Killen, & Taylor, 1989), and clinical (Pohl, Yeragani, Balon, Lycaki, & McBride, 1992) studies have found individuals with panic attacks are more apt to have a history of smoking compared to individuals without a panic attack history. Other investigations suggest smoking often precedes and increases the subsequent risk for developing panic attacks and panic disorder [PD] with and without agoraphobia (Bernstein, Zvolensky, Schmidt, & Sachs-Ericsson, 2007; Breslau & Klein, 1999; Isensee, Wittchen, Stein, Hofler, & Lieb, 2003; Johnson et al., 2000; Zvolensky et al., 2008). There also is evidence to suggest that panic attacks and PD can contribute to the maintenance of smoking (Zvolensky, Schmidt, & Stewart, 2003). For example, panic attacks are associated with more severe nicotine withdrawal (Marshall. Johnson, Bergman, Gibson, & Zvolensky, 2009), shorter durations of abstinence (Zvolensky, Lejuez, Kahler, & Brown, 2004), and overall lower success rates (Piper et al., 2010) following a smoking cessation attempt. Additionally, PD is related to increased motivation to smoke to reduce negative affect (Zvolensky et al., 2005). These data collectively indicate clinically and statistically significant bi-directional relations between smoking and panic. Although there are a variety of factors, including genetic variables and mental and physical health vulnerability, that may impact the link between smoking and panic psychopathology, little is known about the mechainisms underlying their covariance (Zvolensky & Bernstein, 2005). Nicotine withdrawal may serve as one possible mechanism in the explanation of the observed relationships between smoking and panic psychopathology. Nicotine withdrawal reflects symptoms that emerge from a reduction of nicotine in the body via smoking deprivation (Gilbert, 1988). A diverse body of research indicates: (a) smoking deprivation among daily smokers results in a set of prototypical withdrawal symptoms (e.g., anxiety, depression, impatience, difficulty concentrating, and restlessness; Hughes, 2007; Hughes & Hatsukami, 1986; Hughes, Higgins, & Hatsukami, 1990); (b) negative affect is a central feature of such withdrawal (Baker, Piper, McCarthy, Majeskie, & Fiore, 2004; Patten & Martin, 1996); and (c), withdrawal symptoms gradually emerge within minutes after a cigarette has been smoked (Jarvik et al., 2000; Schuh & Stitzer, 1995). Acute and prolonged aversive interoceptive cues (e.g., bodily tension, anxiety) associated with nicotine withdrawal may have important implications for the onset and maintenance of panic psychopathology (Hogle, Kaye, & Curtin, 2010; Zvolensky, Schmidt, & McCreary, 2003). Namely, smokers with PD experiencing smoking deprivation may be more likely to attend to, and catastrophize about, unpleasant, acute nicotine withdrawal symptoms, presumably hastening elevations and delaying recovery from withdrawal states (Abrams, Zvolensky, Dorflinger, & Galatis, 2008). This type of perspective suggests PD may moderate a nicotine withdrawal-panic effect among daily smokers, as acute nicotine withdrawal symptoms may be more likely to be perceived as personally threatening among those with, compared to those without, PD (Zvolensky & Bernstein, 2005). Although there has not been a direct evaluation of PD and nicotine withdrawal on anxious and fearful responding to bodily sensations, a number of indirect sources of evidence have been reported. For example, smokers with PD retrospectively report greater withdrawal symptom severity during past quit attempts compared to individuals without such a history (Marshall et al., 2009; Zvolensky et al., 2004b). There also is a limited body of work that suggests anxiety sensitivity (AS), a core cognitive component of panic psychopathology, may be related to the severity of nicotine withdrawal symptoms across laboratory and clinical studies (Johnson, Stewart, Rosenfield, Steeves, & Zvolensky, in press; Marshall et al., 2009; Mullane, Stewart, Rhyno, Steeves, Watt, & Eisner, 2008; Vujanovic & Zvolensky, 2009). Overall, empirical work suggests acute nicotine withdrawal may be related to increased risk of panic responding, yet direct empirical evidence is lacking for PD. The overarching aim of the present study was to examine whether nicotine withdrawal symptoms elicited by a 12-hour smoking deprivation period (versus no deprivation) among daily smokers resulted in greater fearful responding to, and delayed recovery from, laboratory-induced bodily sensations among those with PD compared to those without PD. In the current investigation, PD was coded categorically, rather than indexed continuously, to facilitate comparability with existing panic psychopathology research, which has consistently employed a categorical classification. Alternatively, although participants were assigned to either smoking deprivation (SMD) or smoke as usual (SAU), this variable was indexed continuously as participants smoking rates, levels of nicotine dependence, and total hours of withdrawal were not standardized, thus, potentially resulting in a broader range of nicotine withdrawal. It was hypothesized that smokers with PD who were experiencing greater levels of nicotine withdrawal, as a result of smoking deprivation, would experience the greatest levels of fearful responding to a 10% carbon dioxide-enriched air (CO2) laboratory procedure, as measured by: (1) intensity of post-challenge panic attack symptoms; (2) change in anxiety focused on bodily sensations from pre- to post-challenge; and (3) rate of recovery from the challenge in terms of anxiety focused on bodily sensations.