اثرات ورزش حاد بر واکنش پذیری چالش CO2

Abstract The present study examined the effects of acute exercise on anxiogenic responding to 65% O2/35% CO2 challenge. Participants (N = 92) were 51 female and 41 male volunteers ranging in age from 17 to 24 (M = 19.43, SD = 1.31). Participants had no history of panic attacks and were randomized to moderate treadmill exercise (i.e., 70% of HRmax) or quiet rest prior to taking a single vital capacity inhalation of 35% CO2/65% O2. Gender and measures of negative affectivity and anxiety sensitivity were included in the design as control variables. Results indicated participants who exercised prior to challenge showed significantly reduced reactivity compared to their counterparts who rested prior to challenge. Importantly, the effect sizes for the advantage of exercise over rest remained in the medium to large range (i.e., partial η2 > .07) after controlling for the effects of gender, anxiety sensitivity, and negative affectivity. These findings are the first to demonstrate that the anti-panic effects of exercise are unique from, and cannot be better explained by, established risk factors of CO2 challenge reactivity.

. Introduction Findings from initial clinical trials point to the efficacy of aerobic exercise for the treatment of panic disorder (Broocks et al., 1998 and Martinsen et al., 1989). It has been proposed that aerobic exercise may exert its effects on panic disorder symptoms, in part, by reducing fear of somatic arousal (Broocks et al., 1998, Otto et al., 2007 and Smits et al., 2007). Specifically, aerobic exercise provides exposure to feared interoceptive cues (e.g., racing heart, rapid breathing, sweating), thereby allowing fears to dissipate (extinguish). Evidence consistent with this mediational hypothesis comes from cross-sectional work indicating that physical inactivity is associated with greater anxiety about bodily sensations (i.e., anxiety sensitivity) both in undergraduate students (McWilliams and Asmundson, 2001) and individuals suffering from panic disorder (Smits and Zvolensky, 2006). More direct evidence comes from a series of randomized controlled (prospective) studies evaluating the efficacy of exercise for individuals with clinical levels of anxiety sensitivity (Broman-Fulks et al., 2004, Broman-Fulks and Storey, 2008 and Smits et al., in press). These experiments have demonstrated that six brief sessions of moderate intensity exercise (i.e., 70% of maximal heart rate [HRmax]) yield significantly greater reductions in anxiety sensitivity compared to a waitlist control or placebo (i.e., low intensity exercise). Furthermore, the improvements in fear of anxiety and related bodily sensations observed with exercise tend to precede subsequent reductions in anxiety. Previous research demonstrates that biological challenges paradigms are useful for evaluating cognitive theories of panic disorder (Schmidt et al., 1996, Schmidt et al., 1997 and Zvolensky and Eifert, 2000). Indeed, these challenges (e.g., sodium lactate infusion, inhalation of high concentrations of CO2, administration of cholecystokinin tetrapeptide [CCK4]) have shown to reliably induce the intense autonomic arousal characteristic of anxiety states such as panic (Bradwejn, 1993, Liebowitz et al., 1984a and Papp et al., 1993), and as such, serve as a working model for the phenomenology of panic disorder (McNally, 1999). Consistent with theoretical accounts that emphasize the role of fear of anxiety and related (interoceptive) sensations in the onset and maintenance of panic disorder (Bouton et al., 2001, Clark, 1986 and McNally, 1990), numerous studies have shown that anxiety sensitivity predicts the degree of anxious responding to biological challenges (Beck et al., 1996, Brown et al., 2003, Feldner et al., 2006, Rapee et al., 1992 and Schmidt et al., 1997), even after controlling for negative affectivity (Zinbarg et al., 2001) and behavioral inhibition (Zvolensky et al., 2001); this anxiety sensitivity-challenge relationship was not observed in two studies, possibly due to a truncated range of variability in levels of anxiety sensitivity (Koszycki and Bradwejn, 2001 and Struzik et al., 2004). Evidence also suggests that the reduced anxiogenic responding to biological challenges that occurs with successful cognitive-behavioral treatment of panic disorder (Gorman et al., 2004 and Shear et al., 1991) may be mediated by reductions in fear of somatic arousal (Schmidt et al., 1997). Accordingly, if the mechanism of change underlying exercise interventions for panic disorder indeed resembles that of cognitive-behavioral interventions (i.e., reduction in fear of somatic arousal; Smits et al., 2004), exercise of moderate intensity should theoretically reduce anxiogenic responding to biological challenge. To date, three controlled studies have investigated the effects of exercise on emotional responding to biological challenge (Esquivel et al., 2008, Esquivel et al., 2002 and Ströhle et al., 2005). Esquivel et al. (2002) randomized 20 healthy volunteers to complete exercise or minimal activity prior to taking a single vital capacity inhalation of 35% CO2/65% O2. Exercise involved cycling on a bicycle ergometer with increasing workload to reach >6 mmol/L of blood lactate concentration, whereas minimal activity involved cycling on the ergometer with continuous (low) workload. Participants completed 12 min of physical activity and the two conditions showed significant differences in blood lactate concentration. Participants who exercised reported significantly reduced challenge reactivity in terms of panic symptoms relative to those in the control condition (Cohen’s d = 1.25). Differences in anxiety responding were in the hypothesized direction, but only approached statistical significance (d = .41). In a separate study, Ströhle et al. (2005) randomly assigned 15 healthy participants to 30 min of treadmill exercise at 70% of maximum oxygen consumption or 30 min of quiet rest prior to receiving an injection of 50 μg of CCK4. Results showed statistically significant and moderate to large differences (ds > .65) between participants in the exercise and control conditions with respect to CCK4 induced panic attacks, panic symptoms, and anxiety. In an attempt to extend the findings of these early studies, Esquivel et al. (2008) recently examined the effects of acute exercise on emotional responding to biological challenge among 18 participants with a diagnosis of panic disorder. Using a similar protocol to that employed in their earlier study, they found that moderate to hard exercise (i.e., up to 15 min of cycling at 80–90% of HRmax) was associated with reduced CO2 reactivity (panic attacks, panic symptoms, and anxiety) relative to very light exercise. Effect sizes observed in this study were large (ds > 1.0). Although promising, extant biological challenge-exercise studies are limited in at least three key respects. First, it is possible that the previously documented exercise effects are attributable to other known risk factors for challenge reactivity. That is, as of yet, there is a lack of empirical evidence that acute exercise incrementally predicts reduced levels of anxiogenic responding to interoceptive sensations above and beyond pre-existing fears of the negative consequences of such stimuli (i.e., anxiety sensitivity), a history of panic attacks (Lynch et al., 1992), or a generalized tendency to react with emotionality to life events (negative affectivity; Hayward et al., 2000). Although previous studies employed randomized controlled designs, sample sizes were small and the measurement or inclusion of these predictor variables was omitted. Hsu (1989) has shown that studies with small sample sizes (such as the 18–20 participants in these previous investigations) have a high probability (53–72% in these previous investigations) of group differences on at least one “nuisance variable” even if participants are randomly assigned to groups. Accordingly, we cannot be confident that the exercise effect could not be better or largely explained by these established risk factors for anxiogenic responsivity. Second, it has not been clear whether the exercise-fear dampening effects to somatic perturbation are similarly evident among males and females. Indeed, there are well-established differences in fear reactivity to bodily sensations, with females compared to males showing greater responding (Kelly et al., 2006). It is not clear whether exercise anxiolysis varies as a function of gender. Survey studies have yielded mixed results, with some reporting a stronger relationship between physical activity and reduced anxiety among women compared to men (Stephens, 1988), while others report a stronger relationship for men relative to women (Bhui and Fletcher, 2000) or no differences based on gender (Schmitz et al., 2004). Investigations of the effects of acute exercise on anxiety have not carefully considered the potentially moderating effects of gender. It is important therefore to empirically evaluate whether females and males are affected equally by acute exercise of moderate intensity in relation to anxious and fearful responding to panic-relevant bodily sensations. And finally, each of the past studies relied on relatively small sample sizes (i.e., Ns < 20). Thus, confidence in a moderate exercise dampening effect for anxious and fearful responding to bodily sensations, both in regard to generalizability and stability of effect size, would be strengthened with replication and extension in a larger sample than in past work. Together, the overarching aim of the present investigation was to replicate and uniquely extend past work on exercise and challenge reactivity. Accordingly, we randomized a large sample (N = 92) of healthy participants with no history of panic attacks to moderate treadmill exercise (i.e., 70% of HRmax) or quiet rest prior to taking a single vital capacity inhalation of 35% CO2/65% O2. Gender and measures of negative affectivity and anxiety sensitivity were included in the design as control variables. We hypothesized that participants randomized to exercise would report reduced anxiogenic responding to CO2 relative to participants in the quiet rest condition, even after controlling for gender, negative affectivity and anxiety sensitivity. Furthermore, we explored the possibility that the effects of exercise would be moderated by gender.

. Results 3.1. Preliminary analyses Means, standard deviations, and correlations among the relevant study variables are presented in Table 1 and Table 2. Baseline levels of each of the study variables and demographic variables were examined for differences between the Exercise conditions. The conditions differed only on baseline API total, with people who were later assigned to the “rest” condition reporting greater symptom severity than those who were later assigned to exercise (t (90) = 2.14, P < .05). Accordingly, baseline API total was used as a covariate in all the analyses reported below (except those analyses including baseline symptom severity as a dependent variable). Table 1. Baseline characteristics by condition Variable Exercise Rest N % N % Female 26 54 25 57 White 37 75 37 84 Inactive 10 21 8 18 M SD M SD Age 19.50 1.34 19.38 1.28 Cardiorespiratory fitness 14.67 2.12 14.54 2.26 PANAS negative 13.36 4.01 12.20 2.81 ASI 11.50 7.32 10.31 6.97 API total⁎ 1.73 1.80 2.91 3.33 API SUDS 4.38 7.96 5.68 9.25 Note: inactive = inactive or little activity other than usual daily activities; cardiorespiratory fitness = MET levels of cardiorespiratory fitness; PANAS negative = positive negative affect scale – negative subscale; ASI = anxiety sensitivity index; and API total = acute panic inventory symptom severity total score. ⁎ The difference between the two conditions is significant at .05 level (two-tailed). Table options Table 2. Zero-order correlations for main study variables PANAS negative ASI API total – T1 API total – T2 API total – T3 API SUDS – T1 API SUDS - T2 PANAS negative ASI 0.51⁎⁎ API total – T1 0.41⁎⁎ 0.39⁎⁎ API total – T2 0.07 0.36⁎⁎ 0.31⁎⁎ API total – T3 0.10 0.32⁎⁎ 0.36⁎⁎ 0.24⁎ API SUDS – T1 0.25⁎ 0.25⁎ 0.49⁎⁎ 0.39⁎⁎ 0.23⁎ API SUDS – T2 0.26⁎ 0.32⁎ 0.29⁎⁎ 0.51⁎⁎ 0.30⁎⁎ 0.55⁎⁎ API SUDS – T3 0.15 0.35⁎⁎ 0.29⁎⁎ 0.19⁎ 0.61⁎⁎ 0.25⁎ 0.49⁎⁎ Note: PANAS negative = positive negative affect scale – negative subscale; ASI = anxiety sensitivity index; API total = acute panic inventory symptom severity total score; API SUDS = acute panic inventory fear SUDS score; T1 = baseline; T2 = post exercise/quiet rest; and T3 = post CO2 challenge. ⁎ Correlation is significant at the.05 level (two-tailed). ⁎⁎ Correlation is significant at the.01 level (two-tailed). Table options 3.2. Effects of exercise on CO2 reactivity Table 3 presents the means and standard deviations on the measures of CO2 reactivity at baseline, after exercise (or rest), and immediately after inhalation. We performed repeated measures ANCOVAs to examine the main study hypothesis. In these analyses, gender and condition (quiet rest/exercise) were between-subjects variables, time was a three-level (baseline [T1], after the exercise (or rest) period [T2], and immediately after CO2 inhalation [T3]) within-subject variable, and anxiety sensitivity3 and negative affectivity were entered as covariates. Separate ANCOVAs were performed for the API total and API SUDS. Table 3. Panic symptoms and fear at baseline, post exercise and post CO2 challenge Variable Exercise Rest M SD M SD Panic symptoms API total – T1 1.73 1.80 2.91 3.33 API total – T2 4.45 2.77 1.57 2.86 API total – T3 8.96 6.07 11.26 6.25 Fear API SUDS – T1 4.38 7.96 5.68 9.25 API SUDS – T2 6.56 13.26 6.59 9.14 API SUDS – T3 22.92 23.45 35.12 25.76 Note: API total = acute panic inventory symptom severity total score; API SUDS = acute panic inventory fear SUDS score; T1 = baseline; T2 = post exercise/quiet rest; and T3 = post CO2 challenge. Table options 3.3. API total Initial analyses indicated that the sphericity assumption of repeated measures ANCOVA was not met (Mauchly’s W = .51, View the MathML sourceχ(2)2=56.79, P < .001). Accordingly, we employed the Greenhouse–Geiser correction ( Greenhouse and Geiser, 1959). Of the two covariates, only anxiety sensitivity was positively related to symptom severity (F(1,86) = 16.77, P < .001, partial η2 = .16; negative affectivity, F < 1.0, n.s.). There was a main effect for time (F(1.35,115.64) = 17.75, P < .001, partial η2 = .17), but, consistent with hypothesis, this main effect was qualified by a significant time × condition interaction (F(1.35,115.64) = 14.71, P < .001, partial η2 = .15). The time × gender interaction approached significance (F(1.35,115.64) = 2.68, P = .09, partial η2 = .03) and the three-way time × condition × gender interaction was not significant (F < 1.0, n.s.). To determine that the increase from post exercise/rest (T2) to post CO2 challenge (T3) varied as function of condition, we repeated the analysis with a two-level within-subjects variable (T2, T3) and entered the T1 API total as an additional covariate. The results revealed a significant time × condition interaction (F(1,84) = 18.84, P < .001, partial η2 = .18). In this model, the time × gender interaction again approached significance, suggesting that females tended to report greater increase in symptom severity as a result of the challenge than males (F(1,84) = 3.36, P = .07, partial η2 = .04). Adding cardiorespiratory fitness as an additional covariate revealed that the difference in the responses of males and females to the CO2 challenge was not a result of fitness differences between the sexes (i.e., the observed relationships did not change). 3.4. API SUDS Because initial analyses indicated that the sphericity assumption of the repeated measures ANCOVA was not met (Mauchly’s W = .45, χ2 (2) = 68.69, P < .001), we used the Greenhouse–Geiser correction. Overall, the pattern of results was similar to that observed for the API total. Only anxiety sensitivity (F(1,86) = 6.68, P < .05, partial η2 = .07), and T1 API total, F(1,86) = 5.94, P < .05, partial η2 = .07), were significant covariates in the model (negative affectivity, F < 1.0, n.s.). The main effect of time (F(1,86) = 7.82, P < .005, partial η2 = .09) was qualified by both significant time × condition (F(1.29,107.97) = 5.16, P < .05, partial η2 = .06), and time × gender (F(1.29,107.97) = 3.88, P < .05, partial η2 = .04) interactions. The three-way time × condition × gender interaction was not significant (F < 1.0, n.s.). A follow-up ANCOVA with a two-level within-subjects variable (T2, T3) and T1 API SUDS entered as an additional covariate revealed that those who exercised responded to the CO2 challenge with a smaller increase in fear than those who rested (F(1,86) = 6.79, P < .05, partial η2 = .08). The time × gender interaction was also significant in this analysis (F(1,86) = 5.82, P < .05, partial η2 = .07), indicating greater responsivity among females compared to males. These results remained significant after controlling for cardiorespiratory fitness. 4