The hyperventilation syndrome in panic disorder, agoraphobia and generalized anxiety disorder

The symptom complex of panic disorder and generalized anxiety disorder suggests an etiological role for hyperventilation. The present study investigates the overlap between DSM-III-R panic disorder, panic disorder with agoraphobia and generalized anxiety disorder with hyperventilation syndrome (HVS). The anxiety disorder diagnoses were based on a structured interview, and HVS syndrome (HVS). The anxiety disorder diagnoses were based on a structured interview, and HVS determined by the so-called hyperventilation provocation test (a brief period of voluntary hyperventilation with recognition of symptoms). The overlap rates with HVS were: 48% for panic disorder, 83% for panic disorder with agoraphobia and 82% for generalized anxiety disorder. However, a pilot study on transcutaneous monitoring of carbon dioxide tension leads us to question the validity of the voluntary hyperventilation method that we used to determine HVS-status. It is unclear whether hyperventilation plays an important role in panic and general anxiety, as our overlap findings suggest. For patients who recognize the symptoms induced by voluntary hyperventilation, the hyperventilation provocation procedure provides a therapeutic means of exposure to feared bodily sensations.     

Panic disorder in the families of patients with normal coronary arteries and non-fear panic disorder.

Patients with non-fear panic disorder (NFPD) meet DSM-III-R criteria for panic disorder, but do not report subjective fear or anxiety. Although apparently common in medical settings, this controversial group is in need of further diagnostic validation. This study assessed family history of panic disorder in patients with chest pain and normal coronary arteries (CP/NCA) and either NFPD, panic disorder with fear, or no panic. It was hypothesized that the two panic disorder groups would have similar, elevated rates of panic disorder in their first-degree relatives, compared to patients without panic. The results support the hypothesis; about 17% of the first-degree relatives of both NFPD and panic disorder patients were diagnosable with panic disorder according to proband interviews, whereas only 4.6% of the first-degree relatives of patients without panic were so diagnosable. These results support the diagnostic validity of NFPD in CP/NCA patients, because such patients had a family history of panic disorder similar to patients with a more classical panic disorder presentation. The lack of fear symptoms and behavior in NFPD may cause panic disorder to be overlooked as a potential cause of somatic symptoms in patients with no medical explanation for their condition.     

Chest pain without coronary artery disease: An exploratory comparison with panic disorder

Recent reports have indicated similarities between patients with persistent chest pain of nonorganic origin and patients with panic disorder. In order to explore this association further, we administered a structured interview and three self-report measures (State-Trait Inventory, Beck Depression Inventory, and SCL90-R) to three subject groups: (1) a sample with persistent chest pain (CP; n=14) who had been screened and found to have normal coronary arteries, (2) a sample of patients with panic disorder (PD; n=14), and (3) a sample of matched normals (n=14). CP patients were considered to be free of coronary artery disease (CAD) following normal cardiac catheterization and/or normal thallium stress tests and were not diagnosed initially with panic disorder. PD patients were diagnosed with a standardized psychiatric interview and were free of organic causes of panic. Using an exploratory data analytic approach, the results indicated that both CP and PD samples reported increased levels of state and trait anxiety (p <.0001), depression (p <.01), and somatization (p <.0001) compared with normals. CP patients differed from PD patients in their less frequent use of anxiolytic medication (p <.01) and lower levels of reported panic anxiety and phobic avoidance (p <.0001). These data suggest that persistent chest pain in the absence of CAD shares some features with panic disorder, yet differs from panic in key ways as well. The results are discussed in light of the role of anxiety in contributing to symptom labeling.This research was supported by Grant 86G-491 from the American Heart Association, Texas Affiliate, to J.G.B. H.T. is the recipient of USPHS Research Career Development Award K04-HL-0122246.     

The hyperventilation provocation test in panic disorder.

Forty-eight patients with DSM-III-R Panic Disorder underwent a hyperventilation provocation Test (HVPT). Twenty-four patients rated the symptoms induced during the HVPT as similar to those occurring during panic attacks in daily life. Contrary to the classical hyperventilation model of panic, no differences were found in respiratory physiology between recognizers and non-recognizers before and during voluntary hyperventilation. Moreover, recognizers and non-recognizers reported comparable levels of panic and hyperventilation symptoms and state anxiety during panic attacks in daily life. Ten of the recognizers also had a panic attack during the HVPT, independent of any differential CO2 alterations. Compared to non-panickers, panickers obtained higher scores for agoraphobia and depression. On the basis of these results, it is concluded that recognizers or panickers do not show a tendency towards hyperventilation, but that reports of severe panic and hyperventilation symptoms are more closely related to the level of anxiety. These results are more consistent with the cognitive model of panic, which emphasizes the patient's tendency to interpret somatic symptoms catastrophically.     

Symptom Attributions Across the Menstrual Cycle in Women with Panic Disorder

Women with panic disorder are likely to experience greater menstrual-specific symptoms (e.g., headaches, cramps) as well as more panic/anxiety-related symptoms (e.g., dizziness, faintness, chest pain, heart pounding), and may be more likely to experience these symptoms during the premenstrual phase. This study examines the attributions women make about the somatic and affective symptoms they experience during the menstrual cycle. Using a 30-day prospective design, women with and without panic disorder monitored physical and affective symptoms. Participants reported on severity of various symptoms and a primary cause for each symptom (menstrual cycle-related, panic/anxiety related, stress-related, health-related). Women with panic disorder reported more panic attacks during the premenstrual phase compared to other cycle phases. They also reported more severe affective and panic symptoms during the premenstrual phase compared to other phases, but did not significantly differ from the comparison group in menstrual symptom severity across the three cycle phases. Although women with panic disorder attributed more panic/anxiety-related causes for their symptoms across the menstrual cycle, they were able to discriminate between panic/anxiety causes and menstrual cycle-related causes. Women with panic disorder may benefit for therapy that focuses on their exacerbation of panic symptoms during the premenstrual phase.     

Hyperventilation and anxiety in panic disorder, social phobia, GAD and normal controls

Patients with DSM-III Agoraphobia, Panic Disorder, GAD, Social Phobia and normal controls underwent a series of experimental procedures and measures to determine whether panic attack patients show a greater tendency towards hyperventilation that is independent from their anxiety levels. Contrary to expectations, the Agoraphobia and Panic Disorder patients did not show significantly lower levels of expired pCO2 at rest than the other anxious or non-anxious groups. However, the panic attack patients did show significantly higher levels of anxiety and hyperventilatory symptoms during a hyperventilation test and during breathing 5% CO2 in air. A strong relationship was found between hyperventilatory symptoms and anxiety in all groups of patients and in the controls. On the basis of these results it was concluded that Agoraphobia and Panic Disorder patients do not show a unique tendency toward hyperventilation, but rather that their hyperventilatory symptoms and perhaps intermittent overbreathing episodes are a function of the high levels of anxiety they experience.     

Response to hyperventilation and inhalation of 5.5% carbon dioxide-enriched air across the DSM-III-R anxiety disorders.

Anxiety disorder patients (n = 198; under criteria of the Diagnostic and Statistical Manual of Mental Disorders; rev. 3rd ed.; American Psychiatric Association, 1987) and nonanxious control subjects (n = 25) underwent challenges of 90 s of voluntary hyperventilation and 15 min of 5.5% carbon dioxide in air. Panic disorder subjects showed a greater subjective response to both challenges than did subjects with other anxiety disorders, who in turn responded more than did control subjects. Furthermore, subjects with panic disorder as an additional diagnosis tended to report more subjective response than did anxiety disorder subjects without panic disorder. The best prechallenge predictor of response to each procedure was a measure of fear of physical symptoms. The findings support previous results that have pointed to a greater fear or anxiety-inducing effect of these challenge procedures in panic disorder patients, as compared with other subjects.     

Physiological and symptom responses to hyperventilation: A comparison of frequent and infrequent panickers

Ten subjects with panic disorder and ten subjects with infrequent panic attacks were assessed during 2 min of voluntary hyperventilation using four measures of physiological arousal (heart rate, upper trapezious EMG, skin conductance, and digital skin temperature). Immediately following hyperventilation, subjects were asked to rate their degree of distress on 13 panic symptoms, derived from DSM-III criteria for panic disorder. Results indicated that frequent panickers had significant overall elevations in trapezious EMG, relative to infrequent panickers, and demonstrated a slight increase in muscle tension following hyperventilation. In contrast, infrequent panickers showed a trend toward greater vasodilation preceding and during hyperventilation, with subsequent vasoconstriction upon resumption of normal breathing. Increases in skin conductance and heart rate were noted for both samples during hyperventilation, as reported in prior research. Symptom distress ratings indicated that the infrequent panickers reported significantly greater distress from dizziness and trembling in response to overbreathing, contrary to prediction. Implications of these findings are discussed in light of current accounts of cognitive and physiological factors in the etiology of panic attacks and panic disorder.This research was supported by Biomedical Research Support Grant #507RR07147, National Institutes of Health.     

Waning of panic sensations during prolonged hyperventilation

Recent theories about panic emphasize that a hyperventilatory positive feedback loop is involved in panic: catastrophic misinterpretation of bodily sensations may trigger anxiety, anxiety may stimulate hyperventilation, hyperventilation may promote the salience of feared sensations etc. Such models leave unexplained how and when panics come to an end. It was hypothesised that panic with hyperventilation may end because pronounced hyperventilation becomes, in the course of time, less powerful in generating perceivable bodily sensations. Twenty healthy subjects hyperventilated forcefully and experienced clear panic symptoms as defined by DSM IIIR. When pCO2 was kept 55% below base line for 90 min, panic symptoms waned. The mean intensity of the symptoms declined as did the number of symptoms occurring. No panic symptoms were observed in the control group (n = 20) who ventilated normally. In so far as hyperventilation is involved in the positive feedback loops that characterize panic, panic attacks may be time-limited because sensations induced by hyperventilation become less salient even if massive hyperventilation continues. As to the explanation of the reported phenomenon, it is suggested that, apart from habituation, local physiological changes due to prolonged hyperventilation may produce a decrease in interoceptive input.     

Animal phobias versus claustrophobias: Exteroceptive versus interoceptive cues

The overall purpose of this investigation was to examine heterogeneity among specific phobias. In particular, the goals were to compare features of fear responding between individuals fearful of claustrophobic situations and individuals fearful of spiders/snakes, and to compare their response to hyperventilation challenges. By so doing, specific predictions were tested in relation to a conceptual model of exteroceptive and interoceptive fear cues. Using a nonclinical sample, 19 subjects with spider/snake phobias, 18 nonphobies, and 9 subjects with claustrophobias were exposed on two separate occasions to a live tarantula or python, a small closet, and a hyperventilation challenge. Dependent measures included subjective anxiety, panic attacks, physical symptoms, cognitive symptoms (or, fear of symptoms) and heart rate. In addition, subjects completed a standardized self-report scale that measures fear of bodily symptoms of arousal. It was found that subjects with claustrophobia reported more physical symptoms and cognitive symptoms than did subjects with snake/spider phobias, in response to their fear-relevant stimulus. In addition, claustrophobic subjects were more fearful of hyperventilation challenges and reported more fear of bodily symptoms, than did snake/spider phobic subjects. Finally, subjects with claustrophobia were as fearful of hyperventilation as they were of their fear-relevant stimulus. Theoretical and empirical implications of these findings are discussed.     

The Role of Cardioprotective Avoidance Beliefs in Noncardiac Chest Pain and Associated Emergency Department Utilization

This study examined cardioprotective avoidance beliefs and general panic/agoraphobia variables among 45 Emergency Department patients with a primary complaint of noncardiac chest pain (NCCP) in the absence of coronary artery disease or other medical explanation. Cardioprotective beliefs about the dangerousness of work and physical activity were assessed with the Fear-Avoidance Beliefs Questionnaire (FABQ). Additional measures assessed complaints of cardiac distress and panic, anxiety sensitivity, panic-related beliefs, agoraphobic avoidance, and depressive symptoms. Hierarchical regression analysis indicated that cardiac distress symptoms are a function of panic symptoms and cardioprotective beliefs concerning both physical activity and work, with 62% of the total variance explained. The predictors also explained 57% of the variance in Emergency Department utilization, which was significantly related to cardiac distress symptoms, number of illnesses, and work-avoidance beliefs. Neither outcome was related to demographics, depression symptoms, general anxiety sensitivity, general panic cognitions, or agoraphobic avoidance. Results suggest that current behavioral understandings of NCCP might be advanced by further examination of cardiac-specific avoidance beliefs and behavior and the potential role these factors play in both symptom experience and medical utilization.     

Restlessness in Generalized Anxiety Disorder: Using Actigraphy to Measure Physiological Reactions to Threat

Generalized anxiety disorder (GAD) is characterized by excessive, uncontrollable worry accompanied by symptoms of physiological arousal. Although individuals with GAD report greater subjective arousal than healthy individuals, they show equivalent or even attenuated physiological reactions to threat. This may result from using physiological measures better suited to fear than anxiety. To test this possibility, 102 adults with and without GAD were assessed for restlessness, a core physiological symptom of GAD. They were exposed to an in vivo threat task designed to elicit anxiety in the laboratory. Throughout the task, restlessness was measured physiologically with actigraphy sensors on both ankles and both wrists, and subjectively with self-report ratings. The GAD group reported higher subjective restlessness than the no-GAD group, and in the subset of cases who had restlessness as a clinically significant symptom, actigraphy scores were reliably elevated as well. However, although actigraphy scores increased with proximity to the threat, the increases did not differ by group. These findings provide initial validation for actigraphy as a novel measure of motor restlessness in GAD. In addition, they underscore the value of measuring restlessness using multiple assessment methods. These methods suggest that, in GAD, restlessness reflects a chronic state of arousal rather than a heightened physiological reaction to threat.     

Health care utilisation in patients with non-cardiac chest pain: A longitudinal analysis of chest pain,anxiety and interoceptive fear

Chest pain can be a frightening experience that leads many to seek medical evaluation. The symptom results in costly health care utilisation. Over half of patients referred for cardiac evaluations of chest pain do not obtain definitive medical explanations for their symptoms; these cases are described as non-cardiac chest pain (NCCP). Some patients with NCCP are not reassured after being informed their chest pain is non-cardiac in origin and seek repeated medical evaluation. Co-morbid anxiety and mood disorders often coexist with NCCP and are associated with health care utilisation. The current study examined chest pain, general anxiety, interoceptive fear and health care utilisation in a sample of 196 chest pain patients near the time of cardiac evaluation (Time 1), and 70 of these patients one year later (Time 2). Results indicate that anxiety and interoceptive fear were significantly associated with health care utilisation at Time 1, and only interoceptive fear (at Time 1) predicted health care utilisation at Time 2. This study develops research in this area by examining the relation of anxiety and health care utilisation longitudinally in patients with NCCP.     

Acute nicotine withdrawal symptoms and anxious responding to bodily sensations: a test of incremental predictive validity among young adult regular smokers

Although previous work has found associations between panic and smoking, little research has investigated potential mechanisms by which smoking may contribute to panic problems. The present investigation evaluated the incremental validity of acute nicotine withdrawal symptoms (elicited by an average of 2 h of nicotine deprivation) relative to negative affectivity, anxiety sensitivity, and nicotine dependence in predicting anxiety responding to 3-min voluntary hyperventilation. The sample consisted of 90 regular smokers (46 females), as defined by smoking 10 cigarettes per day for at least 1 year, recruited through the general community. Consistent with prediction, greater levels of pre-challenge nicotine withdrawal symptoms uniquely predicted post-challenge intensity of panic symptoms and anxiety relative to other established factors. Findings are discussed in the context of how regular smoking may promote panic symptomotology.     

An examination of the relation between traumatic event exposure and panic-relevant biological challenge responding among adolescents

The current study uniquely extended research that has linked traumatic event exposure to panic-spectrum problems among adolescents. It was hypothesized that among 127 adolescents (age range: 10 to 17 years; M = 14.63, SD = 2.24), those who endorsed a history of traumatic event exposure would evidence significantly greater anxious and fearful reactivity to a well-established 3-min voluntary hyperventilation procedure compared to nonexposed individuals. Results were consistent with hypotheses, suggesting traumatic event exposure is associated with anxious and fearful reactivity to abrupt increases in bodily arousal among adolescents. Moreover, consistent with hypotheses, anxiety sensitivity significantly mediated the relations between traumatic event exposure and both self-reported panic symptoms and panic symptoms elicited by the challenge. Future prospective research is now needed to better understand temporal relations between traumatic event exposure and indices of panic and related vulnerability.     

Delineating generalized anxiety: A preliminary investigation

The present study examined the nature of generalized anxiety, which was defined as the constellation of symptoms listed as diagnostic criteria for generalized anxiety disorder in DSM-III-R. Generalized anxiety was assessed by means of a questionnaire that was especially constructed for this study. Although multidimensional scaling of symptoms reported by a clinically anxious sample produced orthogonal anxiety and panic dimensions, many symptoms were common to both dimensions. Whereas worry was found to be the cardinal feature of generalized anxiety, respiratory symptoms were found to associate closely with panic. These dimensions were replicated in a student sample. It is argued that while generalized anxiety symptoms constitute a unique dimension in the field of anxiety disorders, both panic and generalized anxiety may be linked with a basic anxiety response system. The findings also indicated that worry associated more closely with generalized anxiety than did apprehensive expectations. The heuristic value of the findings are discussed in light of the issue relating to an anxiety-panic continuum.     

Anxiety sensitivity and history of panic as predictors of response to hyperventilation

In this study, we examined the effects of anxiety sensitivity on the response to hyperventilation in college students with and without a history of spontaneous panic attacks. Reiss et al.'s (Behav. Res. Ther. 24, 1-8, 1986) Anxiety Sensitivity Index and Norton et al.'s (Behav. Ther. 17, 239-252, 1986) Panic Attack Questionnaire were used to select Ss. Following five min of voluntary hyperventilation, high anxiety sensitivity Ss reported more anxiety and more hyperventilation sensations than did low anxiety sensitivity Ss. A history of panic was only associated with enhanced responding to hyperventilation in Ss with high anxiety sensitivity; low anxiety sensitivity Ss who had experience with panic were no more responsive than low anxiety sensitivity Ss who had never had a panic attack. These findings suggest that high anxiety sensitivity may be a crucial determinant of panic attacks provoked by biological challenges (e.g. hyperventilation, sodium lactate infusion).     

Responses to false physiological feedback in individuals with panic attacks and elevated anxiety sensitivity

Participants with elevated anxiety sensitivity and a history of panic attacks were compared to a low anxiety comparison group with respect to physiological and subjective reactivity to false heart-rate feedback and reactivity to a priming procedure. Whereas accurate heart-rate feedback elicited minimal responses, participants across groups showed significant physiological and subjective responses to false feedback. High risk and low risk participants did not differ in heart-rate responses to false feedback, though panic attack frequency did predict physiological and subjective reactions to false feedback in the high risk group. Self-reported nonspecific anxiety was significantly higher in high risk female participants than in low risk female participants, while males did not different in general subjective anxiety. However, high risk participants reported more panic-specific symptoms during the false feedback task than low risk participants, regardless of the sex of the participant. Therefore, although the experimental paradigm appeared to trigger nonspecific anxiety in high risk female participants, panic attack symptoms in reaction to the task were specific to risk group, not sex, and consistent with hypotheses. Surprisingly, the priming procedure did not influence physiological or subjective responses to false feedback in either group. These results raise additional questions regarding the process and impact of interoception in individuals with panic attacks, and suggest that false perception of internal changes may contribute to risk for panic disorder when exposed to believable cues.     

Book Reviews

Panic attacks and depression frequently co‐occur, and the presence of this co‐morbidity is often associated with worse outcomes compared with each disorder alone. Despite this, not everyone who experiences panic attacks also suffers from depression, suggesting that individual difference factors may play a role in this co‐morbidity. The purpose of this study was to provide a preliminary investigation of two such individual difference factors, examining the role of anxiety sensitivity and lack of emotional approach coping in depressive symptom severity among a non‐clinical sample of uncued panickers. A sample of 79 college students reporting the occurrence of uncued panic attacks within the past year completed a series of questionnaires assessing the lower‐order factors of anxiety sensitivity, emotional approach coping, panic attack frequency, panic‐related disability, panic symptom severity and depressive symptom severity. Participants with more severe depressive symptoms reported greater anxiety sensitivity, panic attack frequency, panic symptom severity, panic‐related disability and lack of emotional approach coping. The particular anxiety sensitivity dimension of fear of cognitive dyscontrol and lack of emotional approach coping emerged as the best predictors of depressive symptom severity. Findings are discussed in terms of their implications for the improved understanding of this co‐morbidity, as well as its treatment.