| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ORIGINAL ARTICLES |
From the Departments of Psychology (J.G.B., J.C.S.) and Physical Therapy, Exercise, and Nutrition Sciences (P.J.O.), State University of New York, Buffalo, NY.
Address reprint requests to: J. Gayle Beck, PhD, Department of Psychology, 230 Park Hall, State University of New York, Buffalo, NY 14260. Email: jgbeck{at}acsu.buffalo.edu
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
METHODS: Seven patients whose naturally occurring panic attacks were characterized by prominent respiratory symptoms (Resp subgroup) were compared and contrasted with seven patients who did not report respiratory symptoms during panic attacks (NonResp subgroup). All were administered a novel 12% O2 challenge and assessed with measures of tidal volume, respiratory rate, end-tidal CO2, anxiety, and panic symptoms.
RESULTS: Although the Resp and NonResp subgroups showed equivalent increases in an-iety and panic symptoms, the Resp subgroup showed greater fluctuation in tidal volume during and after the challenge as well as overall lower levels of end-tidal CO2.
CONCLUSIONS: Our results suggest the importance of panic symptom profiles in determining respiratory responses to a hypo-ic challenge in patients with panic disorder. These findings are discussed in light of current theories of panic disorder, with particular attention to respiratory disturbances in this disorder.
Key Words: panic disorder • respiration • hypoxia • anxiety.
Abbreviations: ADIS-IV = Anxiety Disorders Interview Schedule-IV; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; DSQ = Diagnostic Symptom Questionnaire; ES = effect size; NonResp = nonrespiratory subgroup; PD = panic disorder; PetCO2 = end-tidal CO2; Resp = respiratory subgroup; RR = respiration rate; VT = tidal volume.
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
One approach to the issue of diagnostic heterogeneity is to examine whether PD patients who report different symptom profiles show different responses during a panic attack. Although naturalistic studies of physiological and behavioral responses during panic have been conducted (eg, Ref. 6), alternative approaches, which allow greater experimental control, are preferred. In particular, the biological challenge paradigm has been instrumental in efforts to specify psychopathological features of PD (eg, Ref. 7). This paradigm relies on administration of a panic-inducing agent to PD patients and nonpsychiatric control subjects. To date, numerous studies have been conducted using a range of challenge agents, such as CO2 (inhalation), sodium lactate (injection), and caffeine (oral administration). In each case, PD patients report greater levels of anxiety and more panic attacks than nonpsychiatric control subjects and individuals with other anxiety disorders (8–10).
In some respects, respiratory symptoms are a natural focus for preliminary studies of panic symptom profiles. Klein (2) has highlighted the significance of respiratory functioning in patients with PD , particularly the potential role of suffocation in the genesis and maintenance of recurrent panic attacks. To date, this theory has received indirect support from studies using the CO2 challenge paradigm. For example, Papp et al. (11, 12) have noted that the anxiety reported by PD patients in response to a CO2 challenge is accompanied by larger increases in RR than observed in nonpsychiatric control subjects or patients with social phobia. This exaggerated ventilatory response also continues for a longer period after termination of CO2 inhalation in PD patients than in control subjects (13). These findings are salient because they demonstrate an unusual pattern of ventilation in PD patients. The expected ventilatory response to CO2 inhalation involves an increase in VT (increased size of breath) with little effect on respiratory frequency (14). However, PD patients seem to show the opposite pattern, specifically an increase in RR (eg, Ref. 13). At present, the implications of this unusual ventilatory pattern for understanding PD are unclear, although it is noteworthy that respiratory factors have been implicated as a pathophysiological component of the disorder.
One issue that has not been studied extensively is the role that panic symptom profiles play in response to biological challenges. Although it is clear that CO2 inhalation produces a range of responses, there are only two empirical studies have examined whether panic symptom profiles influenced physiological responding in the laboratory. In the first report, Hegel and Ferguson (15) grouped PD patients into those individuals who reported considerable respiratory symptoms (high respiratory subgroup) and those who did not (low respiratory subgroup) and examined these two groups on respiratory measures during a resting interval. The results indicate that during rest, the high respiratory subgroup showed lower levels of PetCO2 (an indirect measure of the partial pressure of CO2 in the arterial blood) than a group of patients with generalized anxiety disorder and a control group of nonpsychiatric subjects. Although there were no other differences between the high and low respiratory PD subgroups during several laboratory stress tasks, the authors interpreted these findings as potentially supportive of the existence of a PD subtype that is instigated by hyperventilation or other suffocation-related processes. In particular, hyperventilation produces lowered levels of PetCO2 owing to the exhalation of more CO2 than is produced. Thus, lower resting levels of PetCO2 may reflect chronic hyperventilation in this subset of PD patients. In the Hegel and Ferguson study, no differences were noted in RR between these four groups (high respiratory PD, low respiratory PD, generalized anxiety disorder, and nonpsychiatric control).
Biber and Alkin (16) also examined whether panic symptom profiles influenced responding in the laboratory. These authors contrasted 28 patients with PD who reported predominant respiratory symptoms with 23 patients who reported nonrespiratory symptoms during panic. All patients underwent a challenge with 35% CO2. The respiratory subgroup reported a higher rate of panic attacks in response to CO2 challenge, a longer duration of PD, and higher lifetime rates of smoking. Unfortunately, respiratory measures were not reported, precluding a clear understanding of the interrelationship between symptom reports and physiological responding in the laboratory.
Our study was designed to examine how panic symptom profiles influence responding to a suffocative laboratory challenge. This report presents an analysis of secondary data from a new challenge paradigm involving administration of a hypoxic (low O2) challenge. As described by Beck et al. (17), administration of 12% O2 (a hypoxic challenge) for 5 minutes produces greater anxiety for PD patients (N = 14) than for nonpsychiatric control subjects (N = 14). This novel challenge was contrasted with 5 minutes of 5% CO2. The results indicate that although hypercapnia produced somewhat higher levels of anxiety than hypoxia, the PD and control groups did not differ in this regard.
Significant group differences were observed in respiratory functioning, however, with the PD patients demonstrating increased RRs in response to both the hypercapnic and hypoxic challenges, contrary to the expected ventilatory patterns. In our study, the hypoxic challenge was chosen for further examination because the expected respiratory response occurs more slowly than the expected response to hypercapnia. In particular, the expected respiratory response to hypoxia does not occur until extremely low levels of arterial O2 stimulate peripheral chemoreceptors. Once the peripheral chemoreflex is activated, an increase in RR occurs with relatively little change in VT (14). This slower response to hypoxia allows for more clear delineation of differences in respiratory function between patients who report considerable respiratory symptoms during panic and those who do not. Moreover, because previous research has illustrated increased RR in PD patients, the focus on a hypoxic challenge (which is expected to influence RR) is a logical choice.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
coefficients for secondary diagnoses (computed for all patients who were interviewed) were acceptable for generalized anxiety disorder ( = 0.80) and moderate for specific phobia ( = 0.67). Given that this study did not include treatment for panic, patients were not required to discontinue use of psychotropic medications.2 Based on their report of naturally occurring panic on the ADIS-IV, patients were assigned to either the Resp or NonResp subgroup. Patients were assigned to the Resp subgroup if they endorsed four of the five respiratory symptoms identified by Briggs et al. (19) during a typical panic attack. These symptoms included shortness of breath, choking or smothering sensations, fear of dying, chest pain or discomfort, and tingling/numbness. Patients were assigned to the NonResp subgroup if they did not endorse at least four symptoms. The Resp subgroup endorsed an average of 4.14 respiratory symptoms (SD = 0.38) and the NonResp subgroup endorsed an average of 1.71 respiratory symptoms (SD = 1.11).
The Resp sample included six women and one man with an average age of 34.7 years (SD = 7.25 years) and an average duration of PD of 9.86 years (SD = 4.74 years). The NonResp subgroup included six women and one man with an average age of 31.6 years (SD = 9.29 years) and an average duration of PD of 9.14 years (SD = 10.35 years). The groups did not differ in the number of smokers (Resp, N = 3; NonResp, N = 5; 
2= 1.17, NS).
Procedure
After providing informed consent, each participant was administered the diagnostic interview and then returned for the challenge assessment, which took place in a sound- and light-controlled laboratory. On arrival, a mask was placed tightly but comfortably on the participant’s face, held in place with an open-weave cap and Velcro straps.3 Instruments to measure respiratory parameters were placed by a trained assistant, and a 10-minute adaptation interval was allowed. Audiotaped instructions informed the participant that he or she would be inhaling several harmless gas mixtures. The participant was told that some of these gas mixtures would induce bodily sensations but that these changes would be transient. Meteorological balloons were used for gas delivery and were filled in advance so as not to signal the onset of gas administration, permitting single-blind delivery. The balloon was attached to a two-way valve, connected by 1-inch diameter tubing to the inspiratory port of the mask. A pneumotachometer was attached to the expiratory port. An assistant administered each challenge and remained seated behind the participant throughout the procedure.
After a 1 minute baseline period, several gas challenges, including 12% O2 (balance N2), were administered for 5 minutes each in random order. At the completion of each challenge, a 5-minute postchallenge interval was begun. The participant was instructed to rate panic symptoms after minute 1 of this postchallenge interval. A 4-minute rest period followed the postchallenge interval to ensure that parameters returned to baseline. Throughout the procedure, the assistant reminded the participant to provide anxiety ratings. At the completion of the procedure, the participant was debriefed and paid $50.
Measures
Respiratory measures
VT and RR were determined by measuring expiratory air flow using a pneumotachometer (Hans Rudolph model 12946) and differential pressure transducer (Validyne MP-45). Both the pneumotachometer and the pressure transducer were interfaced to a Coulbourn monitoring system through an analog port and integrated using a S76-01 amplifier. Expiratory air flow was integrated to determine VT (expressed in liters), and breaths were counted to determine RR (breaths/min). To extend the findings of Hegel and Ferguson (15), PetCO2 was included. PetCO2 was monitored using a capnograph (Datex model CD 200), which had been calibrated using gases of known CO2 concentration and interfaced to a Coulbourn monitoring system through a S79-02 amplifier. Assessment of PetCO2 involves sampling the plateau of the fractional concentration of CO2 at the end of each expiration and converting this value to milligrams of mercury after adjusting for barometric and water vapor pressure.
Anxiety
Anxiety was assessed using a dial calibrated on a scale of 0 to 100 (0 = no anxiety, 100 = panic). This device involved a potentiometer attached to a mechanical dial, which was interfaced to the Coulbourn system. Sampling was performed in the same manner as for the respiratory measures.
Panic symptoms
Immediately after each inhalation, the participant completed the DSQ (20). This measure asks participants to rate the presence and intensity of DSM-IV panic symptoms using a nine-point Likert scale. Four measures were derived from the DSQ: 1) determination of whether the participant experienced a panic attack (20), 2) the number of overall DSM-IV panic symptoms reported, 3) the number of respiratory symptoms reported (shortness of breath, choking or smothering sensations, fear of dying, chest pain or discomfort, and tingling or numbness), and 4) the intensity of feelings of panic, rated on a scale of 0 to 8 (0 = no panic, 8 = panic attack).
Data Sampling and Statistical Methods
The respiratory and anxiety measures were sampled at a rate of 38 Hz using HS/Videograph software and checked visually for artifacts. Data were averaged to form 1-minute epochs. An exception was the first minute after challenge, where two 30-second epochs were formed because of the rapidity of respiratory changes during this interval. Thus, a total of 12 epochs were included, reflecting the minute preceding the challenge, 5 minutes during the challenge, and the 5 minutes after the challenge.
Data from each measure were examined using a group-by-time (2 x 12) multivariate analysis of variance with repeated measures on the second factor. Significant effects were followed using Tukey’s procedure, with comparison-specific error terms for effects involving the time factor. Following the recommendation of Rosenthal (21), ES values were computed (using partial 
2, which reflects the percentage of variance explained by a given effect) and evaluated using Cohen’s (22) system, in which small effects range from 2% to 12% of variance; medium effects, from 13% to 44%; and large effects, >45% of variance. For the panic symptom measures, a two-factor (group) t test (for the number of panic symptoms reported and the intensity of panic feelings) or 2 analysis (for the presence or absence of panic) was used.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
|
Examination of PetCO2 indicated a significant group effect (F(1,12) = 4.70, p < .05, ES = 28%), which indicated that the Resp subgroup had significantly lower levels of PetCO2 (mean = 32.86, SD = 1.25) relative to the NonResp subgroup (mean = 36.07, SD = 0.93).
Anxiety
Examination of the anxiety measure indicated a significant time effect (F(11,2) = 4.17, p < .0001, ES = 26%; see Fig. 2), which indicated that both subgroups showed a significant increase in anxiety during minute 3 to 4 of the challenge relative to prechallenge levels, with significantly lower anxiety during minutes 4 to 5 after challenge (p < .05).
|
2(1) = 0, NS), with two patients in each group reporting a panic attack during the hypoxic challenge. Likewise, the groups did not differ with respect to the number of DSM-IV panic symptoms experienced during the hypoxic challenge (t = 0.53, NS), with the Resp patients reporting an average of 3.9 symptoms (SD = 3.07) and the NonResp patients reporting an average of 4.9 symptoms (SD = 3.98). The groups did not differ in the number of respiratory symptoms reported (t = 1.17, NS), with the Resp subgroup reporting an average of 1.3 (SD = 1.49) and the NonResp subgroup reporting an average of 2.3 (SD = 1.70) of these five symptoms. Examination of average feelings of panic indicated no group differences (t = 0.00, NS), with the Resp subgroup reporting an average score of 3.1 (SD = 2.97) and the NonResp subgroup reporting an average score of 3.1 (SD = 3.19). |
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
Because the usual and expected ventilatory response to hypoxia involves an increase in RR with little or no change in VT, these findings are particularly intriguing. These data indicate that patients with PD who report prominent respiratory symptoms during naturally occurring panic attacks have erratic ventilation during a laboratory hypoxia challenge. These patients show an unstable response to lowered levels of O2, indicating that they are using an unexpected respiratory strategy (changes in VT) in an effort to compensate for reduced oxygen availability. Although increases in VT allow for more efficient alveolar ventilation relative to increases in RR, the Resp patients were not consistent in this approach. Instead, considerable fluctuation VT was observed in this subgroup, suggesting an inefficient strategy of protecting gas exchange.
The ventilatory pattern shown by the NonResp subgroup also is unusual. As shown in Figure 1, the NonResp subgroup showed an increase in VT considerably before the effects of the hypoxic challenge occurred (within the first minute of the challenge). The absence of a control group comprised of patients with another anxiety disorder is notable when considering these patterns. This type of control group would allow determination of whether the unusual respiratory patterns noted in the Resp and NonResp subgroups are unique to PD or occur in patients with other anxiety disorders. Additionally, replication of these findings would be useful given the small sample sizes.
In general, these findings echo the findings of Hegel and Ferguson (15) and provide preliminary support of the contention that there may be a subtype of PD that involves respiratory disturbances (eg, Ref. 2). The observation that the Resp subgroup showed consistently lower levels of PetCO2 than the NonResp subgroup suggests that there may be subtle differences in CO2 sensitivity between these two types of PD patients. Alternatively, the lower PetCo2 in the Resp subgroup may be the consequence of alterations in central neuromodulators of respiratory timing, resulting in the observed tendency toward an increase in RR in these patients.
Unexpectedly, the Resp and NonResp subgroups did not differ in the level of anxiety produced by the challenge or in their endorsement of panic symptoms. Because the two groups were selected on the basis of differences in panic symptom profiles in the natural environment, one could expect similar differences to occur during the challenge, much as was reported by Biber and Alkin (16). It is possible that this unexpected lack of differences is due to the stimulus qualities of the challenge. In particular, because the low O2 challenge slowly creates a suffocative state, it does not resemble a naturally occurring panic attack, which comes on suddenly and appears "out of the blue." Regardless of whether stimulus qualities were responsible for the lack of obtained differences in anxiety and panic symptoms, it is clear that laboratory investigation of panic symptom profiles should take into account both physiological and psychological processes because these two response domains do not necessarily covary.
Despite methodological limitations, the present results warrant some confidence in light of the obtained ES values. Additionally, continued investigation of hypoxic challenges with PD patients would be interesting given that no other investigators have used this approach despite some discussion in the literature (23). Thus, the current findings support the salience of disturbed respiration for some individuals with PD. It is possible that consideration of individual differences in ventilatory patterns among PD patients may serve to clarify the relationship between respiration and panic. Because one cannot determine whether respiratory disturbances are a cause or consequence of anxiety using panic challenge paradigms, the presence of individual differences in panic symptom profiles provides a useful alternative avenue for study. Given that some PD patients do not report prominent respiratory symptoms during naturally occurring panic, how do these individuals differ in basic respiratory functioning, at rest and in response to a panic-inducing challenge, from patients who complain of pronounced dyspnea and smothering sensations during panic? The answer to this question could greatly advance the understanding of etiological and maintaining factors of PD.
|
ACKNOWLEDGMENTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
|
NOTES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
2 Within the sample, five patients (36%) were taking no medications, five (36%) were taking anxiolytic agents, one (7%) was taking an antidepressant, and three (21%) were taking a combination of anxiolytic and antidepressant medications. Within the Resp and NonResp subgroups, medication use was reported by five and four patients, respectively. Despite the use of these medications, all patients had experienced panic attacks in the month preceding assessment.
3 This configuration was selected to avoid artifacts produced by other means of gas administration, particularly claustrophobic reactions.
Received for publication October 5, 1999.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONNOTESACKNOWLEDGMENTSREFERENCES |
|---|
This article has been cited by other articles:
 |
|
 |
|
  K. M. Oltmanns, H. Gehring, S. Rudolf, B. Schultes, S. Rook, U. Schweiger, J. Born, H. L. Fehm, and A. Peters Hypoxia Causes Glucose Intolerance in Humans Am. J. Respir. Crit. Care Med., June 1, 2004; 169(11): 1231 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Moynihan and R. N. Gevirtz Respiratory and Cognitive Subtypes of Panic: Preliminary Validation of Ley's Model Behav Modif, September 1, 2001; 25(4): 555 - 583. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
