حساسیت اضطراب و واکنش پذیری35٪ دی اکسید کربن در بیماران مبتلا به اختلال هراس

Abstract Objective: The present study examines the possible relationships between anxiety sensitivity (AS) and reactivity to the 35% carbon dioxide (CO2) challenge in panic disorder (PD). Methods: One-hundred eight patients with PD underwent the 35% CO2 challenge and completed the Anxiety Sensitivity Index (ASI). Multiple regression analyses were applied to evaluate the role of AS as a predictor of CO2-induced anxiety. Results: Fifty-six patients with PD showed high AS scores, whereas 48 showed medium scores and 4 low scores. ASI scores significantly predicted symptomatological reaction to CO2 but not subjective induced anxiety. Conclusion: These findings suggest that the fear of anxiety-related bodily sensations was related to the symptomatological reactivity to CO2 but did not seem to play a crucial role in the modulation of the subjective anxiogenic/panicogenic response to hypercapnia in patients with PD.

Introduction Panic-provoking procedures provide closed systems capable of elucidating panic disease mechanisms [1], and one of the most thoroughly investigated experimental procedures used to induce anxiety and panic is the inhalation of hypercapnic gas mixtures [2]. Single or double breath inhalations of 35% carbon dioxide (CO2) have been reported to induce anxiety and panic in patients with panic disorder (PD) [3], [4], [5], [6] and [7], but the degree of anxiety reactivity reported is not homogeneous. Almost 50% of patients with PD shows a very strong reaction to CO2 similar to, or even worse than, the feelings experienced during spontaneous panic attacks [6], while others, around 20–25%, have little or no reaction [8]. The reasons for this heterogeneity have not yet been fully investigated. We have recently [8] reported an association between 35% CO2 sensitivity and familial vulnerability to PD. Patients with positive responses to 35% CO2 showed a higher morbidity risk than patients with negative responses. Yet this factor alone was not adequate to fully explain the heterogeneity of CO2 responses in patients with PD. Among the factors that could explain this heterogeneity, anxiety sensitivity (AS) may play a significant role [9]. AS reflects the fear of anxiety-related bodily sensations that arises from cognitive misinterpretation leading to the belief that these symptoms might have harmful consequences. For example, subjects with high AS may believe that rapid heartbeats signify an impending heart attack, whereas subjects with low AS will merely regard them simply as unpleasant [9]. Many studies have reported that AS is a dispositional construct conceptually distinct from trait anxiety [10], [11], [12] and [13] and is not interchangeable with measures of general anxiety like the State–Trait Anxiety Inventory (STAI) for trait anxiety [13] and [14]. Although PD may exacerbate AS, nonclinical subjects who have never experienced panic attacks show relevant beliefs about the harmfulness of anxiety symptoms. High AS might develop in ways other than subjective experiences with panic attacks, e.g., through misinformation about heart disease or after watching someone die of a heart attack [9], [15], [16] and [17]. High AS might constitute a cognitive risk factor for the development of PD [9], [18] and [19] and might be a predictor of the anxious response to panic-provoking challenges [9] and [20]. Few studies have investigated the relationships between CO2 challenges and AS, and the results are contrasting. Koszycki and Bradwejn [21] reported that there was no correlation between AS and most of the dimensions of behavioral reactivity to 35% CO2. Rapee et al. [22] reported that AS was the only significant predictor of 5.5% CO2-induced fear in patients with anxiety disorders. Telch and Harrington [23] reported that subjects with high AS who had never experienced panic attacks exhibited rates of 35% CO2-induced panic, which were comparable to those of patients with PD. AS has been reported to be an element that can be used to predict the response to CO2 challenges in healthy subjects [24] and [25], as well as in a mixed sample of controls and patients with PD [26]. Finally, AS has been reported to be associated with the tendency to panic in response to voluntary hyperventilation [14], [27] and [28]. The main aim of the present study was to investigate the possible relationships between AS and the responses to 35% CO2 inhalations in patients with PD.

Results Table 1, Table 2 and Table 3 report the results of the study. Among the investigated patients, 67 (62%) experienced an induced panic attack to the 35% CO2 challenge and 41 (38%) did not. Only 4 (7%) of a total of 41 not-panickers had low (ASI9) AS scores. Panickers and not-panickers were not significantly different for age (33.2±12.4 and 30.2±9.7 years, respectively), age at onset (26.8±8.6 and 25.1±7.6 years, respectively), and STAI-1 scores (47.1±15.9 and 49.9±13.5, respectively). No significant differences were found for ASI scores comparing panickers (26.9±8.9) and not-panickers (26.7±10.5). Fifty-six patients with PD (52%) had high ASI scores, 48 (44%) medium, and 4 (4%) low scores. Of the four patients with low ASI scores, one was a panicker and three were not-panickers. Multiple regression analyses (Table 2) showed that ASI was a significant predictor of the symptomatological reaction to CO2, expressed as TSS after CO2 and ΔTSS. In particular, ASI was predictive of the somatic symptomatological response, expressed by SSS after CO2 and ΔSSS, while it was not able to predict significantly cognitive symptomatology induced by CO2, expressed by CSS after CO2 and ΔCSS. CO2-induced anxiety, expressed as VAS-A after CO2 and Δ%VAS-A, was not significantly predicted by ASI scores (Table 3). Table 1. Panickers and not-panickers to 35% CO2: anxiety sensitivity and CO2-induced anxiety Not-panickers (n=41) Panickers (n=67) t test (df=1,106) ASI scores 26.7±10.5 26.9±8.9 ns VAS-A before CO2 32.1±25.2 31.3±20.7 ns VAS-A after CO2 33.6±27.6 72.0±19.0 t=−8.6, P<.001 Δ%VAS-A −3.8±47.3 60.6±23.3 t=−9.4, P<.001 TSS before CO2 6.0±7.0 5.2±5.1 ns TSS after CO2 12.3±10.1 18.0±7.6 t=−3.4, P<.002 ΔTSS 6.3±9.3 12.8±6.5 t=−4.3, P<.001 ΔSSS 5.1±7.7 10.8±2.2 t=−4.6, P<.001 ΔCSS 0.6±1.7 1.2±1.8 ns Table options Table 2. Factors predicting symptomatological response to CO2: results from multiple regression analyses (β scores) Predictors ΔTSS TSS after CO2 ΔSSS SSS after CO2 ΔCSS CSS after CO2 F=10.9, df=3,104, P<.001 F=3.3, df=3,104, P<.03 F=3.6, df=3,104, P<.02 F=8.9, df=3,104, P<.001 F=1.6, df=3,104, P=ns F=12.9, df=3,104, P<.001 ASI 0.24±0.11* 0.28±.10** 0.23±0.11* 0.24±0.10* 0.12±0.11 0.11±0.09 TSS before CO2 −0.32±0.11** .17 ± .10 SSS before CO2 −0.33±0.11** 0.19±0.10 CSS before CO2 −0.09±0.10 0.36±0.09** STAI score 0.09±0.10 0.18±0.09 0.09±0.10 0.16±0.10 0.16±0.10 0.20±0.09* * P<.05. ** P<.01. Table options Table 3. Factors predicting subjective anxiety response to CO2: results from multiple regression analyses (β scores) Predictors Δ%VAS VAS-A after CO2 F=0.7, df=3,104, P=ns F=6.9, df=3,104, P<.001 ASI 0.11±0.11 0.08±0.10 VAS-A before CO2 −0.04±0.11 0.32±0.10* STAI score 0.08 ±0.11 0.09±0.10 * P<.0003.