A REVIEW OF PSYCHOLOGICAL FACTORS ...of the factors/processes involved with anxious responding at the psychological level of analysis can be developed and integrated with biological

Clinical Psychology Review, Vol. 21, No. 3, pp. 375–400, 2001Copyright © 2001 Elsevier Science Ltd.Printed in the USA. All rights reserved

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375

A REVIEW OF PSYCHOLOGICALFACTORS/PROCESSES AFFECTING ANXIOUS

RESPONDING DURING VOLUNTARY HYPERVENTILATION AND INHALATIONS OF

CARBON DIOXIDE-ENRICHED AIR

Michael J. Zvolensky and Georg H. Eifert

West Virginia University

ABSTRACT.

Despite advances in our understanding of the nature of anxiety-related respond-ing during periods of elevated bodily arousal, it is not necessarily evident by what psychologicalmechanisms anxiety is produced and maintained. To address this issue, researchers have increas-ingly employed biological challenge procedures to examine how psychological factors affect anx-ious responding during elevated bodily arousal. Of the challenging procedures, hyperventilationand inhalations of carbon dioxide-enriched air have been among the most frequently employed,and a relatively large body of literature using these procedures has now accumulated. Unfortu-nately, existing reviews do not comprehensively examine findings from hyperventilation and in-halations of carbon dioxide studies, and only rarely the methodological issues specific to thesestudies. To address these issues, we review the voluntary hyperventilation and carbon dioxide-enriched air literature in order to identify the primary methodological issues/limitations of this re-search and address the extent to which psychological variables influence anxious responding tosuch challenges. Overall, we conclude challenge research is a promising paradigm to examine theinfluence of psychological variables in anxious responding, and that such work will likely be en-hanced with greater attention to psychological process issues. © 2001 Elsevier Science Ltd.

KEY WORDS.

Biological challenge, Anxiety, Panic disorder.

HISTORICALLY, RESEARCHERS HAVE employed a variety of aversive stimuli in lab-oratory studies of anxiety. Although many of these stimuli have functionally aversiveproperties, few produce responses that resemble naturally occurring symptoms ofanxiety. Specifically, traditional aversive preparations do not necessarily constituteecologically valid fear-relevant stimuli because they do not produce the type of intense

Correspondence should be addressed to Michael J. Zvolensky, now at the Department of Psychi-atry, Brown University, Providence, RI 02906. E-mail: [email protected]

376 M. J. Zvolensky and G. H. Eifert

autonomic arousal characteristic of anxiety states such as panic. Thus, the use ofshock and other types of tactile aversive stimulation have limited value in the study ofanxiety (Eifert, Forsyth, Zvolensky, & Lejuez, 1999). To address this concern, psycho-pathology researchers have employed other laboratory agents that can produce in-tense bodily arousal that mimics the autonomic activity that is a defining feature ofanxiety-related responding (Fraser & Wilson, 1918). For example, researchers haveused carbon dioxide-enriched air (CO

2

) to study various facets of anxiety neurosis(Cohen & White, 1951; Harris, 1954; LaVerne, 1953; Meduna, 1947). Collectively,strategies that produce sensations that mimic naturally occurring anxiety states are re-ferred to as “biological challenges” (McNally, 1994).

Since the 1980s, biological challenge methodology has increasingly been applied asboth a laboratory model for evoking anxious responding, and as a potential diagnosticmarker for anxiety disorders, particularly Panic Disorder (PD). A number of differentbiological challenges have been employed, including Voluntary Hyperventilation(VH), inhalations of CO

2

, infusions of cholecystokinin-tetrapeptide, sodium lactate,isoproterenol, flumazenil, and oral administrations of caffeine and yohimbine, amongothers (e.g., injections of adrenaline). Although biological factors were originally heldresponsible for adverse reactions to these tests (Nutt & Lawson, 1992), recent researchhas indicated that psychological variables serve at least an equally important role (Bass& Gardner, 1985; Margraf, Ehlers, & Roth, 1986; Wientjes & Grossman, 1994).

Despite theoretical advances in our understanding of the general psychologicalcomponents involved with anxiety-related responding, it is often not clear by what psy-chological mechanisms emotional changes occur (McNally, 1995). That is, research-ers have characterized the general psychological components of anxious responding(e.g., diagnostic differences), but have not necessarily identified the specific factors/processes involved with fear acquisition and maintenance. Thus, it is difficult to deter-mine which psychological mechanisms are linked to the development of psychopatho-logical anxiety conditions.

The high degree of internal validity of biological challenge investigations permitscausally oriented hypothesis testing, which is critical for identifying the psychologicalmechanisms involved with anxious responding (McNally, 1999). Indeed, researcherscan discover theoretical relations among psychological variables that cannot be isolatedin the natural world (Mook, 1983). With such information, more comprehensive accountsof the factors/processes involved with anxious responding at the psychological level ofanalysis can be developed and integrated with biological and behavioral components.There are a number of chief reasons for identifying and better understanding the psy-chological processes involved with anxious responding during elevated bodily arousal(van den Hout & Griez, 1982a). First, heightened somatic activity is a characteristic ofall anxiety disorders, manifesting as either a panic attack, rapidly rising arousal, or lessintense generally heightened arousal (Barlow, Chorpita, & Turovsky, 1996; Westra &Stewart, 1988). Second, worry and distress about somatic sensations is relevant tomany clinical syndromes, including PD, illness phobias, certain specific phobias, som-atization-related disorders, and Posttraumatic Stress Disorder (PTSD), among others(Eifert, Bouman, & Lejuez, 1998). Finally, the fundamental nature of psychologicalprocesses can be identified in nonclinical persons. Thus, researchers can identify psy-chological factors/processes that may be premorbidly associated with increased riskfor developing an anxiety disorder (Newman, Moffitt, Caspi, & Silva, 1998).

Of the biological challenges, VH and inhalations of CO

2

are perhaps the most fre-quently employed. Yet, existing reviews do not comprehensively examine findings

Biological Challenge and Anxiety 377

from the VH and CO

2

literature, particularly findings from studies completed in thelast 5 years (Clark, 1993; Rapee, 1995; Sanderson & Wetzler, 1990; Shear, 1986; van denHout & Griez, 1983). Further, because researchers often discuss the results of differ-ent biological challenge studies together, methodological issues specific to VH andCO

2

studies have infrequently been addressed (see Sanderson & Wetzler, 1990, for anexception with 5% CO

2

challenge). Taken together, a review of the VH and CO

2

chal-lenge studies is an important endeavor. Although others have reviewed aspects ofchallenge research exclusively as it pertains to PD (e.g., Clark, 1993), we discuss thisliterature in a more broad context to reflect its applicability to anxiety-related re-sponding in general.

Our aim is to review the VH and CO

2

literature in order to identify the primarymethodological issues that may limit our understanding of psychological processesduring bodily arousal, and to address the extent to which psychological variables influ-ence anxious responding to such challenges. To provide a background for this review,we first define VH and CO

2

and describe their theoretical relations to anxious re-sponding. We then review the research using these tests in order to identify the extentto which particular psychological factors/processes are related to anxiety-related re-sponding. Based upon our review, we address the major methodological limitations ofthis research and offer suggestions for future development in this arena. We concludeby addressing the major conclusions regarding the influence of psychological factors/processes related to anxious and fearful responding during states of bodily arousal.

HYPERVENTILATION AND CARBON DIOXIDE CHALLENGES

The primary aim of the respiratory system is to provide oxygen (O

2

) to tissues that per-form bodily functions, a process that involves both the removal of O

2

from the air(i.e., inhalation) and CO

2

from the body (i.e., exhalation). The innervation and orga-nization of the respiratory system make it particularly vulnerable to emotional re-sponding (Fried & Grimaldi, 1993). Indeed, breathing is under the control of the cen-tral nervous system (autonomic control) and is regulated, in part, by skeletal muscles(voluntary control); these separate control mechanisms serve homeostatic functionsrelated to metabolism and behavior, both of which help organize responses to envi-ronmental challenges and opportunities.

Hyperventilation

Hyperventilation, defined as minute ventilation that exceeds metabolic demand, is afunction of respiration rate, tidal volume, or both (Levitzky, 1995). Minute ventilationis the product of respiration rate (i.e., breaths per epoch) and tidal volume (i.e.,amount of air inhaled per breath). Acute hyperventilation produces a number of phsi-ological changes, beginning with a reduction in the partial pressure or arterial CO

2

(PaCO

2

) to a level below 35 torr (i.e., hypocapnia; normal range: 35–45 torr). Hyper-ventilation also leads to alkalosis, an elevation in pH in the blood and cerebrospinalfluid, to a point that exceeds 7.5 (normal range: 7.35–7.45). Due to this pH elevation,O

2

is delivered less efficiently to cells as a result of an increased rate of binding be-tween hemoglobin and O

2

. If intense and sustained, hypocapnia and alkalosis can ini-tiate a series of bodily changes associated with vasoconstriction and possibly cardiovas-cular reactivity that help compensate for decrements in O

2

. These physiological


changes, in turn, produce anxiety symptoms. When hyperventilation is chronic, pHreturns to normal as a function of kidney-based cellular changes, although PaCO

2

lev-els typically remain low throughout the prolonged overbreathing (Levitzky, 1995).

Hyperventilation and anxiety-related responding.

Hyperventilation is related to anxiety ingeneral and panic in particular in a number of ways. First, symptoms produced by hy-perventilation—such as dyspnea—are some of the most common physical sensationsthat accompany panic attacks (Cox, Swinson, Endler, & Norton, 1994). Second, per-sons with PD also report more of these sensations than persons with other anxiety dis-orders (Salkovskis, Warwick, Clark, & Wessels, 1986). Third, persons with PD havelower PaCO

2

levels compared to persons with other anxiety disorders and nonclinicalcontrols (Gorman et al., 1990), although these results have not always been replicated(Zandbergen, van Aalst, de Loof, Pols, & Griez, 1993). Fourth, breathing retrainingdirected, in part, at increasing diaphragmatic (deep) as opposed to thoracic (shallow)breathing has been generally successful in reducing the frequency of panic attacks(Han, Stegen, De Valck, Clement, & Van de Woestijne, 1996).

Hyperventilation has been suggested to be critical in the production of somaticsymptoms and the development of clinical anxiety conditions (Carr, Lehrer, Hocron,& Jackson, 1996; Huey & West, 1983; Margraf, 1993). For example, Ley (1989) hassuggested that hyperventilation and the inability to terminate respiratory distress maylead to panic attacks. Further, persons who chronically hyperventilate are suggested tobe at greatest risk for panic attacks and PD because their low PCO

2

levels increase thechance of hypocapnic state and acute hyperventilation (see Ley, 1989 for a review).Despite the relation between overbreathing and panic, however, not all instances orcases of hyperventilation lead to panic attacks or PD (Garssen, de Ruiter, & van Dyck,1992). Nonetheless, VH can induce anxiety symptoms and therefore is a useful provo-cation methodology.

VH tests.

Voluntary hyperventilation involves breathing in excess of metabolic de-mand (Fried & Grimaldi, 1993; van den Hout, Boek, van der Molen, Jansen, & Griez,1988). Research suggests that end tidal PaCO

2

and duration of overbreathing exert in-dependent effects on symptom profiles (Hornsveld, Garssen, & van Spiegel, 1995). Inregard to breathing duration, nearly all symptoms appear after 3 minutes of VH(Hornsveld et al., 1995). Further, VH that lasts for less than 3 minutes may be insuffi-cient in producing arousal, whereas a reduction in symptoms and an increase in fa-tigue may result when overbreathing for extended periods of time (e.g., 60 minutes;van den Hout, De Jong, Zanderbergen, & Merckelbach, 1990). In regard to PaCO

2

, a50% drop in end tidal PaCO

2

from baseline to 3 minutes is associated with increasedarousal, whereas a less than 50% PaCO

2

drop in that same time frame is not (Horns-veld & Garssen, 1996; Hornsveld, Garssen, Dop, & van Spiegel, 1990). One week test-retest reliability for self-reported symptoms produced by 3 minutes of VH is good(Lindsay, Saqi, & Bass, 1991), although little is known about reliability data for otherdurations.

Carbon Dioxide

According to Levitsky (1995), increased levels of CO

2

in inhaled air results in hyper-capnia, an increase in PaCO

2

to a level above 45 torr, and respiratory acidosis, a decre-ment in pH below 7.3. Both peripheral and central chemoreceptors detect accumulat-


ing levels of CO

2

and subsequently increase respiration, most often via tidal volume;this response typically is associated with secondary phsiological changes such as in-creases in heart rate (see Levitsky, 1995 for a review). Overall, the increase in ventila-tion per unit of CO

2

concentration is referred to as CO

2

sensitivity (Papp, Klein, &Gorman, 1993).

Sensitivity to increases in CO

2

has been suggested to be a risk factor for PD (Papp,Klein, & Gorman, 1993). According to Klein’s (1993) suffocation alarm theory of PD,for example, some persons with PD are characterized by a hypersensitive CO

2

monitorthat produces suffocation-based alarms in PD patients. Specifically, rising concentra-tions of CO

2

and environmental stimuli (e.g., elevators) that signal suffocation set theoccasion for intense anxiety and panic (Klein, 1993).

CO

2

and anxiety-related responding.

A variety of evidence is consistent with Klein’s the-ory. First, elevations in CO

2

produce respiratory distress (Gorman et al., 1984). Sec-ond, suffocation fear predicts fear responding during bodily arousal (Rachman & Tay-lor, 1993). Third, an exaggerated respiratory response is associated with spontaneouspanic attacks (Briggs, Stretch, & Brandon, 1993). Finally, some PD patients appear tomaintain low CO

2

levels by chronically hyperventilating (Carr et al., 1996). Yet, PD pa-tients do not exhibit less fear and panic to challenges that lower PCO

2

compared tochallenges that raise PCO

2

(Schmidt, Telch, & Jaimez, 1996), and cognitive-behav-ioral treatment appears to be equally effective for suffocation panickers and nonsuffo-cation panickers (Taylor, Woody, Koch, McLean, & Anderson, 1996). Given these in-conclusive findings, future research will need to continue to clarify the validity ofKlein’s theory.

CO

2

tests.

Researchers have used various concentrations of CO

2

, ranging from 4% to65%, with durations ranging from less than 5 s to 20 min. Typically, higher CO

2

con-centrations are delivered for less time; for example, 5% CO

2

typically is administeredsteadily for 15 min, 20% CO

2

for 20–25 s, and 35% CO

2

in a single vital capacitybreath. These different strategies produce slightly different responses in terms of theonset and duration of symptoms, with low CO

2

levels (range: approximately 4%–9%CO

2

) producing gradual and sustained arousal, and high CO

2

levels (greater than10%) producing more of an abrupt, acute response (Forsyth & Eifert, 1998). In allcases, CO

2

produces hypercapnia and respiratory acidosis over time, although tempo-rary respiratory alkalosis may occur shortly after large CO

2

doses (e.g., 35% CO

2

; Lev-itsky, 1995). Overall, it is the production of autonomic sensations that appears to benecessary for an anxious response. In fact, regardless of CO

2

concentration and fre-quency of presentation, nonclinical and clinical populations report the induced sen-sations to be similar to naturally occurring anxiety symptoms (Ley & Walker, 1973;Rapee, 1994), although CO

2

induction does not increase the chance of developing ab-normal behavior (Harrington, Schmidt, & Telch, 1996; Wolpe, 1987).

There is a wide diversity in the procedural aspects of CO

2

administration. As one ex-ample, researchers have used different methods of gas administration, ranging from agas mask, to a breathing canopy, to Read rebreathing (i.e., breathing with a mouth-piece while nose breathing is occluded by a clip). These different administrationmethods may have different physiological effects, as even CO

2

concentrations of thesame percentage often differ in other aspects of gas concentration (i.e., balance of ox-ygen and nitrogen; Gorman et al., 1988). Additionally, different administration proce-dures may have different psychological effects. For example, a breathing canopy may


be more likely to evoke suffocation-related concerns compared to a gas mask. Beyondthese methodological considerations, we also found no parametric studies that havedirectly evaluated the degree to which different types of CO

2

administration produceanxiety and fear. As such, it is necessary to exercise caution in comparing resultsacross studies, as anxious responding may differ as a function of a variety of method-ological factors (e.g., gas concentration).

PSYCHOLOGICAL FACTORS IN HYPERVENTILATION AND CARBON DIOXIDE CHALLENGE STUDIES

Diagnostic Differences

Although differences in challenge responding between diagnostic conditions doesnot indicate casual psychological mechanisms, we begin by clarifying disorder-baseddifferences to challenges because they are helpful in suggesting what psychologicalprocesses/factors may be involved.

Hyperventilation studies.

Persons with PD report greater anxiety and experience morepanic attacks during VH compared to nonclinical persons with and without a historyof panic attacks, persons with generalized anxiety disorder, and persons with socialphobia (Beck & Scott, 1987; Gorman et al., 1994; Griez, Lousberg, van den Hout, &van der Molen, 1987; Holt & Andrews, 1989a, 1989b; Rapee, Brown, Antony, & Bar-low, 1992). However, recent research indicates persons with PD and persons with ani-mal, height, blood/injection, and driving-specific phobias report levels of anxiety sim-ilar to VH (Antony, Brown, & Barlow, 1997). In the majority of studies, physiologicalresponding among clinical and nonclinical persons during VH does not differ be-tween groups, and panic attacks are rarely reported (Bass, Lelliott, & Marks, 1989;Beck, Berisford, & Taegtmeyer, 1991; Craske & Barlow, 1990; Rapee, 1986; Whittal &Goetsch, 1995).

CO

2

studies.

PD patients and their first-degree relatives respond with elevated anxietyto CO

2

(range: 5%–35% CO

2

) compared to nonclinical controls (Papp, Klein, & Gor-man, 1993; Perna, Bertani, Caldirola, & Bellodi, 1996). Despite early suggestions thatPD patients are more responsive to CO

2

than persons with other anxiety disorders,this hypothesis appears only to be partially accurate. Indeed, persons with PD reportgreater anxiety than persons with generalized anxiety disorder, obsessive-compulsivedisorder, animal-specific phobias, and mood disorders to 5% and 35% CO

2

(Holt &Andrews, 1989a, 1989b; Perna, Barbini, Cocchi, Bertani, & Gasperini, 1995; Perna,Bertani, Arancio, Ronchi, & Bellodi, 1994; Rapee, 1986; Verburg, Griez, Meijer, &Pols, 1995), yet they do not differ from persons with social phobia, or situational ornatural environment-specific phobias (Caldirola, Perna, Arancio, Bertani, & Bellodi,1997; Caldirola, Perna, Arancio, Cocchi, & Bellodi, 1995; Gorman et al., 1990; Ver-burg, Griez, Meijer, 1994). Similar to VH, when differences in response to CO

2

are ob-served, they typically are apparent for self-report but not phsiological measures. Gor-man et al. (1990) suggests this finding could be due to the robust visceral responseproduced by CO

2

(i.e., ceiling effect) and/or elevated anticipatory anxiety prior tochallenge in all participants. Nevertheless, rates of panic attacks for persons with PDand situational phobias are higher during 5.5% CO

2

compared to nonclinical persons(Antony et al., 1997).


It is important to note that researchers have not thoroughly assessed for the pres-ence of specific types of psychological factors, comorbid conditions, psychotropicmedication use via blood screenings, and menstrual cycles in the diagnostic groupcomparison studies. Given that all these factors influence anxious responding to chal-lenge (Perna, Brambilla, Arancio, & Bellodi, 1995), it is possible that variables may ac-count, in part, for the observed findings. Overall, susceptibility to VH and CO

2

doesnot appear to be a diagnostic marker for PD (Antony et al., 1997; Sanderson & Wetz-ler, 1990). However, persons that respond with elevated anxiety to these challengesappear to share in common a fear of interoceptive stimuli associated with arousal(Lelliot & Bass, 1990). For example, persons with blood-injection-injury, height, situa-tional, and natural environment-specific phobias report that they dislike bodilyarousal and fear the consequences (e.g., fainting) of contact with fear-relevant stimuli(Merckelbach, de Jong, Arntz, & Schouten, 1993). Thus, the relative degree of con-gruity between challenge-induced symptoms and pre-existing fears related to bodilysensations (e.g., heart palpitations), danger (e.g., suffocation fear), and specific ex-pectancies (e.g., going crazy), may be particularly likely to evoke an intense response(Hamm, Vaitl, & Lang, 1989; Himle, Crystal, Curtis, & Fluent, 1991).

Along these lines, we now turn to a discussion of psychological factors that havebeen suggested to amplify anxiety-related responding during bodily arousal and per-haps serve as vulnerability dimensions for developing certain anxiety disorders.

Psychological Correlates

Trait anxiety.

Trait anxiety is the tendency to respond anxiously to stressors in gen-eral, as measured by the State-Trait Anxiety Inventory (STAI; Spielberger, Gorsuch,Lushene, Vagg, & Jacobs, 1983). Although trait anxiety is elevated among those withPD and those at risk for PD, it has not been shown to distinguish those with PD fromthose with other anxiety disorders (McNally, 1996). High trait-anxious persons reportsignificantly greater anxiety compared to persons low in trait anxiety during VH, de-spite similar levels of physiological reactivity (Whittal & Goetsch, 1995; Whittal, Goetsch,& Suchday, 1994; Van den Bergh, Vandendriessche, De Broeck, & Van de Woestijne,1993). High trait-anxious persons and nonclinical panickers also have been found torecord a number of panic attacks similar to VH, although significantly less than per-sons with PD (Whittal et al., 1994). Given that the groups also differed in Anxiety Sen-sitivity Index (ASI) level, it is not clear what specific psychological factors accountedfor these results. Indeed, because research suggests trait anxiety does not account fora greater amount of unique variance relative to the ASI in predicting response to chal-lenge (McNally & Eke, 1996), it may be that Anxiety Sensitivity (AS) is accounting fora large percentage of variance in regard to the observed findings.

State anxiety.

State anxiety pertains to a current anxiety level (e.g., “right now, at thismoment”) rather than a mean anxiety level across situations. When state anxiety is as-sessed before (and in close temporal proximity) exposure to a stressor, it constitutesanticipatory anxiety (Griez, de Loof, Pols, Zandbergen, & Lousberg, 1990; Rapee etal., 1992). Thus, anticipatory anxiety and state anxiety may represent slightly differentconstructs as a function of time. Nevertheless, researchers rarely make a distinctionbetween the two in challenge research, and measure them with the same types of self-report inventories (e.g., SUDs; STAI-state; Suess, Alexander, Smith, Sweeney, & Mar-ion, 1980; van den Hout & Griez, 1982b).


Results of research concerning the role of state anxiety to VH and CO

2

are not consis-tent. For example, some researchers suggest elevated state anxiety is neither necessarynor sufficient for a heightened anxiety response to challenge (Griez, Zandbergen, Pols,& de Loof, 1990; Papp et al., 1989; Perna, Bertani, Arancio, Ronchi, & Bellodi, 1995;Verburg et al., 1994). Other research has found that high levels of anticipatory anxietyprior to VH and CO

2

challenge increases anxious responding to challenge (Gormanet al., 1984; Rapee & Medoro, 1994; Roth et al., 1992). For example, in a repeated35% CO

2

challenge, high ASI persons reported greater levels of anxiety prior to eachreadministration of gas compared to low ASI persons (Beck, Shipherd, & Zebb, 1996).It is possible that anticipatory anxiety may explain, in part, challenge response whenconsidered with additional psychological factors (Margraf & Ehlers, 1989). For exam-ple, although high anxiety-sensitive persons respond with greater anxiety to VH com-pared to low anxiety-sensitive persons, they also report significantly greater preexperi-mental anxiety (Liebman & Allen, 1995). Thus, perhaps it is the interaction betweenstate anxiety and a preexisting fear of bodily sensations/trait anxiety that may be themost potent predictor of challenge response. This question awaits future research at-tention.

In regard to assessment of state anxiety, some researchers have suggested that pre-experimental differences in state anxiety should be taken into consideration by usingpre-post challenge change scores (Margraf & Ehlers, 1989). Others argue that be-cause anticipatory anxiety is a theoretical useful construct in itself, attempts to ac-count for baseline differences may obscure an accurate understanding of what factorspredict challenge response (Rapee & Medoro, 1994). Although the decision to usechange scores will need to be based on the particular research hypothesis beingtested, the independent assessment of baseline state anxiety in the laboratory settingprior to challenge exposure (at a separate testing session) and immediately prior tothe challenge (on the day of testing) is necessary to elucidate the relative contribu-tions of these variables.

Beyond trait and state anxiety, preexisting fears pertaining to bodily sensations andanxiety (e.g., anxiety sensitivity, suffocation fear) have been identified as being relatedto challenge response. It is to this topic that we now turn.

Anxiety sensitivity.

AS, defined as the fear of anxiety symptoms (i.e., physical threat)based on the belief that they are dangerous, is measured by the ASI (Reiss, Peterson,Gursky, & McNally, 1986). Persons with PD score significantly higher on the ASI thanpersons with other types of anxiety disorders (e.g., generalized anxiety disorder) de-spite these same individuals reporting similar levels of trait anxiety (Taylor, Koch, &McNally, 1992). High ASI children and college students report greater anxiety andnumber of panic sensations to VH compared to their low ASI counterparts (Baker,MacDonald, Stewart, & Skinner, 1998; Holloway & McNally, 1987; Liebman & Allen,1995; Unnewehr, Schneider, Margraf, Jenkins, & Florin, 1996). Further, this differentialpattern of anxious responding is apparent irrespective of trait anxiety and panic attackhistory (Asmundson, Norton, Wilson, & Sandler, 1994; Donnell & McNally, 1989;Dowden & Allen, 1997). The ASI is arguably the most reliable predictor of anxious re-sponding to VH relative to other physical threat measures and trait anxiety (Eke & Mc-Nally, 1996; McNally & Eke, 1996; Rapee et al., 1992). Despite these reliable self-reportfindings, researchers have not found differences in autonomic activity between groups,nor the occurrence of panic attacks in VH studies (e.g., Asmundson et al., 1994).

AS also affects anxious responding to CO

2

, although considerably less CO

2

research


has been conducted relative to VH. High ASI nonclinical persons report greater levelsof anxiety and more panic symptoms compared to low ASI persons during repeatedtrials of 35% CO

2

(Beck et al., 1996). Beck et al., for example, found that high ASIpersons show less habituation for preinhalation anxiety ratings and postinhalationskin conductance levels to CO

2

presentation relative to low ASI persons, but not forheart rate or muscle tension. Although the ASI is a significant predictor of anxiety to5.5% and 20% CO

2

in persons with and without anxiety disorders (Rapee et al., 1992),self-report of panic symptoms but not autonomic conditioned responses differ as afunction of preexperimental ASI levels during 13% and 20% CO

2

challenge (Forsyth,Palav, & Duff, 1999). Thus, although high ASI persons are likely to report CO

2

to beanxiety-evoking, they may not necessarily be at an increased risk for fear conditioning.

Fear of fear.

Although related to AS, fear about physical symptoms associated with au-tonomic activity (i.e., fear of fear) is conceptually distinct from beliefs about the harm-ful consequences of anxiety-related stimuli. In particular, fear of fear is specific tophysical sensations associated with arousal, whereas AS relateds to fear about the con-sequences of these symptoms (see McNally, 1994, pp. 115–119). As indexed by theBody Sensations Questionnaire (BSQ; Chambless, Caputo, Bright, & Gallagher,1984), fear of fear is elevated in persons with PD compared to nonclinical controlsand persons with other anxiety disorders (Chambless & Gracely, 1989). Schmidt andTelch (1994) found that nonclinical persons with high BSQ scores report greater anx-iety during and after VH compared to low BSQ persons, although no physiological dif-ferences nor panic attacks were observed. Interestingly, the BSQ has not been foundto be a significant predictor of response to 5% CO

2

challenge (Lynch, Bakal, White-law, Fung, & Rose, 1992). This finding may be due to the fact that participants in theLynch et al. study evidenced relatively low levels of pre-experimental state/anticipa-tory anxiety. Thus, although these participants feared physical sensations produced bythe challenge, they may not have been sufficiently concerned about the challenge dueto methodological variables in that particular study.

Suffocation fear.

Suffocation fear is a specific fear of suffocation-related sensations andsituational factors that may occasion them. Suffocation fear is measured by the Suffo-cation Fear Scale (SFS; Rachman & Taylor, 1994). Consistent with Klein’s (1993) suf-focation alarm theory of PD, the SFS accounts for an amount of variance comparableto the ASI during VH (Eke & McNally, 1996; McNally & Eke, 1996). Although suffoca-tion fear may, in some respects, be more closely related to claustrophobia than PD,people high in the SFS respond more fearfully to respiratory distress produced bybreathing through a straw than low SFS persons (Rachman & Taylor, 1993). In a re-lated way, nonclinical persons with claustrophobic fears reported significantly more

DSM-III-R

panic sensations during VH compared to nonclinical persons with snake/spider fears and nonfearful controls, although there were no differences for heartrate (Craske & Sipsas, 1992). Additionally, approximately 10% of the persons withclaustrophobia fears reported a panic attack during VH, whereas the other groups didnot (Craske & Sipsas, 1992). Because the relation between fear of suffocation and fearof entrapment has not been directly tested nor theoretically explicated, research com-paring persons differing in these characteristics is necessary to clarify their relativecontributions to particular anxiety disorders (e.g., claustrophobia, PD).

In addition to specific threat-related psychological factors, a personal history ofpanic may affect the degree of anxiety experienced during biological challenge.


Panic attacks.

A panic attack constitutes a direct learning experience that may in-crease the probability of developing clinical syndromes, particularly PD (Ehlers,1995). Nonclinical panickers have been found to report greater anxiety compared topersons without a history of panic attacks to VH (Whittal et al., 1994), and panic fre-quency predicts response to 5% CO

2

in PD patients (Lynch et al., 1992). Perna, Gabri-ele, Caldirola, and Bellodi (1995) recently found that nonclinical panickers reportsimilar levels of anxiety to 35% CO

2

compared to PD patients. However, other studieshave not found such self-report differences (Schmidt & Telch, 1994). Futher, in noneof the investigations has panic attack history affected physiological reactivity to VHcompared to persons without such history (Asmundson et al., 1994; Asmundson, San-dler, Wilson, & Norton, 1983; Sandler, Wilson, Asmundson, Larsen, & Ediger, 1992;Schmidt & Telch, 1994; Whittal & Goetsch, 1995; Whittal et al., 1994).

In regard to methodological related to panic screening, self-classification of panic his-tory is a less sensitive procedure relative to other assessment methods such as structuredinterviews (Brown, 1994). Thus, studies that rely strictly on self-classification will be lesslikely to contain “clean samples” (Barlow, Brown, & Craske, 1994). Further, little isknown about specific aspects of the panic history itself. Indeed, researchers have rarelyused a diagnostic interview to ascertain panic history, not specified the particular type ofpanic experience (e.g., cued-uncued, expected-unexpected), and only in rare instancesconsidered other aspects of panic history such as frequency and intensity of attacks. It ispossible that more controlled research will indicate what particular type of panic attackmight affect anxious responding more than others (Street, Craske, & Barlow, 1989). Asone example, persons with a history of uncued-unexpected panic attacks may have anincreased susceptibility to respiratory-based arousal due to lower levels of perceived pre-dictability for negative emotional experiences (Mineka & Zinbarg, 1996).

There is a large degree of heterogeneity of panic attacks in regard to symptom pre-sentation (Barlow et al., 1994). Thus it is possible that panic attacks may be related tochallenge, depending on the criterion adopted in defining and screening panic history.At first glance, it appears the vast majority of challenge research indicates that partici-pants (particularly nonclinical persons) often do not experience a panic attack despiteelevated somatic arousal during challenges (Rapee, 1995). Yet, Forsyth, Eifert, andCanna (1999) have suggested that this research may be conservatively biased, given thatpanic attacks have not been studied in an idiographic fasion. Using SUDs ratings and acomposite index of autonomic arousal, these researchers classified panic attacks in non-clinical persons as either prototypic (anxiety and arousal), cognitive (anxiety and mini-mal arousal), and nonfearful (minimal anxiety and arousal) to multiple inhalations of13% and 20% CO

2

-enriched air. Results indicated that over 90% of the prototypic panicgroup and over 70% of the cognitive panic group reported a panic attack during thestudy. These results did not drastically vary when liberal or conservative criteria wereused in defining panic. Further, over 80% of the participants responded in a relativelystable manner across the inhalations in regard to their panic subtype classification.Thus, it appears that a substantial number of persons do panic during challenge, butpresent differently in terms of how they panic (Forsyth et al., 1999).

Acquisition and Maintenance Factors/Processes

Aside from individual difference factors, other types of psychological processes havebeen examined using challenge procedures. These learning experiences pertain to


how information about interoceptive events are processed, and therefore are closelytied to theoretical accounts of fear acquisition and maintenance.

Classical conditioning. In Pavlovian conditioning fears can be acquired by pairing Neu-tral Stimuli (NS) with aversive Unconditioned Stimuli (US) that evoke Uncondi-tioned Response (UR; Cahill, Carrigan, & Evans, 1998). Classical conditioning hasonly recently been investigated using VH and CO2 as the US. Results suggest that re-peated VH of at least a 2-minute duration and/or presentations of CO2 (range: 7%–20% CO2) can serve as a reliable US to condition responses to odors, animated videoimages, and auditory signals (Forsyth & Eifert, 1998; Forsyth, Eifert, & Thompson,1996; Gallego & Perruchet, 1991; Kartsounis & Turpin, 1987; Lejuez, 1997; Van denBergh, Kempynck, Van de Woestijne, Baeyens, & Eelen, 1995; Van den Bergh, Stegen, &Van de Woestijne, 1997, 1998).

There are a number of findings from VH and CO2 conditioning research that arerelevant to understanding the origin and maintenance of anxious responding. First,interoceptive sensations can function as conditioning events in fear onset (Forsyth &Eifert, 1998; Forsyth et al., 1996). Second, fear conditioning is a function of the inten-sity of the Conditioned Response (CR), where a more intense response increases theprobability of fear onset (cf. Burish & Carey, 1986). For example, Forsyth and Eifert(1998) found 20% CO2 produces a more intense response compared to 13% CO2,and CRs to 20% CO2 are more easily acquired, of a higher magnitude, and more resis-tant to extinction in nonclinical persons (see also, Forsyth et al., 1996). Third, neutralstimuli that share common characteristics with the US (“belongingness”), and thoseassociated with physical threat, are more easily conditioned compared to NS that arenot (Forsyth et al., 1996; Van den Bergh et al., 1995, 1997).

Future research that clarifies more specific components of fear conditioning maybe particularly useful in terms of understanding how Pavlovian conditioning influ-ences fear onset. First, researchers will need to identify what other psychological fac-tors contribute to CR intensity and strength. For example, given that research indi-cates CR strength depends on the affective evaluation of the US (Davey, 1989), it willbe important to determine how evaluative responses affect challenge-induced fearconditioning. Given that conditioning-based fear acquisition may be more relevantfor certain disorders than others (e.g., dental phobia; Moore, Brodsgaard, & Birn,1991), it would be helpful to extend challenge-based conditioning to these othertypes of fears. Finally, it will also be necessary to determine the parameters of the con-ditioning process itself. Specifically, clarifying what aspects of a learning history affectthe chance of acquiring fears (e.g., previous experience with an unpaired NS may af-fect subsequent conditioning when that same stimulus is paired with a US).

Along these lines, both predictability and controllability of threatening events aretwo psychological process variables that may affect the degree to which anxiety andfear is produced in the immediate situation.

Predictability and controllability. Predictability and controllability of threatening eventshave been linked to the development, maintenance, and treatment of pathologicalanxiety. Laboratory experiments with animals in particular, have found unpredictableand/or uncontrollable aversive events to have a more pronounced impact on anxietythan predictable and/or controllable aversive events (Mineka & Zinbarg, 1996). Fur-ther, prolonged experience with uncontrollable and unpredictable aversive eventsmay increase individual susceptibility for chronic anxiety (Chorpita & Barlow, 1998).


Research suggests that the relation between prediction and control is unidirectionalsuch that control most often implies prediction, yet prediction does not necessarilyimply control (see Zvolensky, Lejuez, & Eifert, 2000). Thus, although both predictionand control have independent effects, we discuss these variables in the same sectiongiven the natural overlap between them.

Zvolensky and colleagues recently examined whether preexperimental differencesin perceived predictability of anxiety-related events mediates response to 3-min VH innonclinical persons. Using the Perceived Predictability Index (PPI; Zvolensky, Eifert,Lejuez, Hopko, & Forsyth, 1999) to select extreme groups, those persons with a ten-dency to view events as unpredictable reported significantly greater affective and cog-nitive distress compared to those with higher levels of perceived predictability. Consis-tent with theoretical accounts of PD (Barlow, 1988), these results indicate differencesin predictability perceptions may determine, in part, anxious responding duringstates of arousal. It should be noted that although the groups were selected on the ba-sis of high and low prediction levels, the groups did not differ in regard to preexperi-mental anticipatory anxiety or somatic arousal. Thus, the observed differences for thedependent measures appear to be a function of preexisting differences in perceivedpredictability, and not just differences in anxiety-based negative emotionally.

In experimental studies, predictability typically refers to the identification of a stim-ulus that signals the onset or offset of an aversive event (Zvolensky, Lejuez, & Eifert,2000). Lejuez (1997), using a single-subject design, found that when the onset of ad-ministrations of 20% CO2 was unsignaled, nonclinical participants had greater levelsof operant response suppression during CO2 presentations (“behavioral disruption”)and higher self-reported anxiety compared to signaled gas presentations. These re-sults suggest that unpredictable periods of autonomic arousal that an individual can-not control may contribute to elevated anxiety in a manner that is similar to the un-predictable panic attacks experienced by persons with PD (Craske, 1991). Telch andHarrington (1992) found similar results in college students with no history of panicattacks who differed in fear of bodily sensations during CO2 challenge. Half the partic-ipants in each group were informed that CO2 would be relaxing, and the other halfwere informed that it would produce symptoms common to high arousal. Results indi-cated that a significantly greater number of high anxious persons experienced a panicattack during CO2 inhalation if they were expecting relaxation and not arousal. Theseresults suggest the unexpected (i.e., unpredicted) experience of intense bodilyarousal in persons who fear the consequences of anxiety symptoms will be particularlylikely to produce panic.

Lejuez and colleagues recently conducted two studies examing predictability with aforced-choice experimental procedure. This methodology gives the participant thechoice between experiencing predictable or unpredictable aversive stimulation, withthe primary dependent measure being the distribution of these choices. From a theo-retical perspective, if unpredictable bodily sensations truly are more aversive thanwhen such events are predictable (Barlow, 1988), then one would expect persons toreliably prefer predictable over unpredictable occurrences of such events.

In the first study, three PD patients were exposed to repeated inhalations of unpre-dictable and predictable inhalations of 20% CO2 using a single-subject design (Lejuez,Zvolensky, Eifert, Sorrell, et al., 1999). Our results did not indicate a uniform prefer-ence for predictable over unpredictable administrations of 20% CO2-enriched air.Specifically, one participant showed a reliable preference for onset predictable CO2,whereas two participants did not. Although these results in no way definitively argue


against a preference for predictability, they may suggest that predictability prefer-ences could at least be partially affected by individual characteristics. In the secondstudy examining nonclinical participants, females showed a significantly greater pref-erence for predictability compared to males, as did high anxiety-sensitive participantscompared to their low anxiety-sensitivity counterparts (Lejuez, Eifert, Zvolensky, & Ri-chards, 1999). Specifically, high anxiety-sensitive females showed the greatest prefer-ence for predictability, high anxiety-sensitive males and low anxiety-sensitive femalesshowed moderate preference for predictability, and low anxiety-sensitive males wereindifferent. Overall, these results suggest that predictability preferences appear to bestrongly related to preexisting fears and gender.

In regard to controllability, researchers generally define control as the terminationof the onset or offset of aversive stimulation (Foa, Zinbarg, & Osalov-Rothbaum, 1992;Zvolensky, Lejuez, & Eifert, 2000). Accordingly, control is relevant to anxious re-sponding insofar as individuals can either control or have perceived control over theemotional experience of anxiety, or attempt to manipulate environmental stimuli thatare responsible for the experience (Eifert, Coburn, & Seville, 1992). Although bothtypes of control are relevant to anxiety disorders (Chorpita & Barlow, 1998), research-ers only have directly manipulated control over laboratory preparations (e.g., CO2)and assessed control over both emotional/bodily experiences and environmentalevents in challenge studies (Zvolensky, Lejuez, & Eifert, 1998).

Sanderson, Rapee, and Barlow (1989) found that persons with PD who had the “il-lusion” they could stop the presentation of 5.5% CO2-enriched air reported less anxi-ety and panic symptoms, and experienced a fewer number of panic attacks comparedto persons without the illusion of control. Van den Bergh et al. (1993), on the otherhand, found that nonclinical participants differing in trait anxiety (high and low) whohad control over the offset of a 5-min 5.5% CO2-enriched air did not differ from par-ticipants in the no-control condition in regard to anxious responding. To clarify thesediscrepancies, Zvolensky and colleagues examined how a lack and loss of offset con-trol over the repeated presentation of 20% CO2 inhalation affects anxious respondingin high ASI nonclinical persons (Zvolensky, Eifert, Lejuez, & McNeil, 1999; Zvolenskyet al., 1998). The findings from these investigations indicate (a) that participants with-out control report significantly more anxiety, and more intense panic experiencescompared to their yoked counterparts with control; and (b) the anxiety-related effectof a lack of control persists in future situations where a control option is available. In-terestingly, whereas all high ASI participants demonstrated a Stroop interference ef-fect for general (e.g., coffin) compared to specific (e.g., dizzy) physical threat word-types preexperimentally, this effect persisted only for participants who originally hadoffset control. Thus, the attentional bias for physical threat disappeared under ele-vated state anxiety that was induced by not having control, whereas having control de-creased anxiety and therefore increased the chance of interference (Mathews & Se-bastian, 1993).

Interestingly, participants rarely utilized their control option across CO2 offset con-trol studies. Lejuez, O’Donnell, Wirth, Zvolensky, and Eifert (1998), however, foundthat nonclinical participants reliably will respond to avoid the onset of repeated pre-sentations of 20% CO2 (i.e., onset control; Zvolensky et al., 2000). Research suggeststhat both offset and onset control are functionally similar, that is, both responses areaimed at preventing/eliminating aversive stimulation (Zvolensky et al., 2000). Thus, itis possible that directional sets may influence control-oriented responding. For in-stance, in the Lejuez et al. experiment, the opportunity to avoid CO2 (onset control)


was never mentioned, thereby eliminating the possibility of implicit experimeter de-mand. In contrast, in the offset control studies, participants were given more explicitdirections as to how to escape CO2 presentation once gas was presented (Zvolensky, etal., 1998), and were even encouraged to resist this option to examine the influence ofperceived control (Sanderson et al., 1989). If participants in the offset control studieshad exercised their control option, the results may have dramatically differed. In theSanderson et al. study, for example, the offset control contingencies were inoperative;thus, if participants formerly with perceived control actually exercised this option,they would have experienced a loss of control. In any event, researchers will need todirectly examine the relative contributions of perceived and actual control over envi-ronmental and bodily stimuli in order to better understand the nature of this theoret-ically important process variable.

Beyond predictability and controllability, researchers have explored the extent towhich contextual manipulations related to threat (i.e., danger, safety) influence re-sponding to challenges. It is to this topic that we now turn.

Danger processes. Salkovskis and Clark (1990) were the first to directly manipulate per-ceived threat during VH. In this study, nonclinical persons were provided with a nega-tive or positive interpretation of VH-induced sensations. Despite equivalent levels ofarousal due to VH, those in the negative interpretation condition experienced the re-sulting sensations as significantly more anxiety-evoking compared to their counter-parts; no panic attacks were reported in either condition. Similar findings wereobatined in a study by Margraf and Ehlers (1989), in which PD patients were either in-formed that they would undergo a “panic attack test” or a “fast-paced breathing task.”The group receiving the “panic” directional set reported more panic symptoms, al-though this same group also differed preexperimentally in anticipatory anxiety, ap-parently due to the experimental manipulation. van den Hout and Griez (1982a) alsofound that PD patients who were told that they would experience tension during CO2

challenge experienced a nonsignificant increase in tension compared to their coun-terparts who were told they would experience relaxation.

Rapee, Mattick, and Murrell (1986) found that PD patients who were provided withan explanation concerning the effects of 50% CO2 inhalation responded with lessanxiety and panic compared to their counterparts given less information concerningthe effects of the CO2-enriched air (see van der Molen, van den Hout, Vroemen, Lous-berg, & Griez, 1986, for related findings using lactate infusion). As information con-cerning the CO2 was not as threatening compared to the limited explanation condi-tion, these findings support the hypothesis that increased threat contributes toanxious responding. In a recent study, however, Papp, Welkowitz, Martinez, Klein,Browne, & Gorman (1995) failed to replicate Rapee et al.’s (1986) results with PD pa-tients using VH, 5% CO2, and 7% CO2. Despite closely following the Rapee et al.(1986) instructional manipulation, this was not a systematic replication of the Rapeeet al. investigation, because a variety of methoological factors such as CO2 concentra-tion and administration technique differed these studies.

Overall, there is relatively consistent evidence that experimental manipulations thatdecrease physical threat decrease anxious responding. It is important to note, how-ever, that this conclusion is necessarily somewhat speculative, given that researchershave not measured “episodic physical threat levels.” That is, the ongoing threat pro-cesses have not been identified (e.g., “how threatened do you feel, right now?”). Asanxiety-related emotional processing generally is considered to be a continous rather


than discrete event (Foa & Kozak, 1986), repeated within-session measurement will benecessary to tap these episodic changes.

Even when people are at risk for responding with anxiety and fear to challenges,there may be protective factors that attenuate such risk. Access to safety-related infor-mation has been one process variable that may function in this regard.

Safety processes. According to Seligman and Binik (1977), safety signals refer to stimulithat (a) signal the offset of an aversive stimulus, or (b) signal the absence of the onsetof aversive stimuli. Interestingly, because aversive events such as panic attacks rarelyare entirely signaled or unsignaled in the natural environment (Craske, 1991; Craske,Zarate, Burton, & Barlow, 1993), “true” safety signals typically are not available. None-theless, persons with anxiety disorders often report less anxiety in the presence ofstimuli that are associated with greater amounts of safety (Rachman & Bichard, 1988).Thus, the degree of perceived safety may be a function of the correlation between pre-vious instances of an aversive event and signals for that event.

Rapee, Telfer, and Barlow (1991) directly manipulated safety cues (e.g., presence ofa professional during challenge, or professional leaving abruptly during the proce-dure) during a 5.5% CO2 challenge in persons with PD. Although no main effect wasapparent between conditions, post hoc analyses indicated that participants with lesssafety information reported greater anxiety than their counterparts. In a similar way,Carter, Hollon, Carson, and Shelton (1995) found that persons with PD reported lessanxiety and physiological activity during 5.5% CO2 in the presence of a safe person.Schmidt and Telch (1994) also found that safety information reduced reported anx-ious responding in nonclinical persons during VH. Future research will need to ex-tend previous findings by addressing the role of safety signals in different populationsand during repeated CO2 challenge that more closely mimic recurrent panic attacks.

Taken together, it appears that if an experimental manipulation can successfullydecrease safety levels, there is an increased chance of elevations in anxious respond-ing. What is less is clear is how safety signals exert their effects. For example, if the ef-fects of safety are due to the perception that the participants can minimize/eliminatethreatening stimulation, then this variable seems highly related to aspects of offsetcontrol (Carter et al., 1995). Future research that directly examines such issues is nec-essary to truly clarify the influence of safety processes in regard to anxiety-related re-sponding.

Because anxiety can change as a function of repeated exposure alone, it is necessaryto discuss research related to the modulation of anxious and fearful responding. In-deed, such information provides a useful context in which to evaluate the role of par-ticular psychological variables/processes in anxious responding over time.

Challenge treatment processes. A substantial amount of evidence suggests exposure con-ducted in vivo and/or imaginally to feared stimuli is a necessary component of treat-ment for anxiety disorders (Marks, 1987). Meduna (1947) was the first to use CO2 asan exposure treatment for anxiety neurosis. Since that time the repeated presentationof CO2 (range: 35%–65% CO2) has been employed as a fear reduction strategy in ex-posure-based treatments, primarily for PD (e.g., Haslam, 1974; Latimer, 1977; La-Verne, 1953; Meduna, 1954; Slater & Leavy, 1966; van den Hout, van der Molen,Griez, Lousberg, & Nansen, 1987; Wolpe, 1954). The majority of the CO2 treatmentstudies indicate that the repeated presentation of CO2 in safe contexts can reduce anxi-ety in the laboratory, and to a lesser extent in naturalistic settings (Wolpe, 1958). In


fact, CO2 has been found to reduce the frequency of panic attacks, panic-related fears,and in some instances, agoraphobic avoidance in PD patients (Beck & Shipherd,1997; van den Hout, van der Molen, Griez, Lousberg, & Nansen, 1987). Despite thepromising findings of the CO2 treatment studies, these investigations are typically un-controlled, involve small sample sizes, and do not include any follw-up assessment.Thus, conclusions regarding the efficacy of CO2 as an exposure technique are limitedat the present time.

A number of theoretical propositions have been suggested to account for fear re-duction during CO2 exposure, including reciprocal inhibition, habituation, extinc-tion, cognitive schemata, and opponent-processes, although none are without limita-tions (see Eifert et al., 1992). Recently, Beck and colleagues have suggested that theremight be two distinct change processes related to fear responding to 35% CO2—habit-uation and sensitization. This conclusion is related to the finding that PD patientsclassified as “nonhabituators” based upon their self-reported postinhalation anxietyduring a session of repeated presentations of 35% CO2, show less anxiety during sub-sequent exposure compared to PD patients classified as “habituators” (Beck,Shipherd, & Zebb, 1997). These findings are consistent with early suggestions thatthose who profit most from exposure are persons who demonstrate habituationwithin an exposure session (Borkovec & Sides, 1979). In addition to within-session ha-bituation, at least two other psychological mechanisms related to fear reduction maywarrant further investigation in CO2 treatment studies. First, those who react with ele-vated anxiety during exposure are most likely to show later reductions in anxious re-sponding (Lang, Melamed, & Hart, 1970). In contrast, persons who respond with lessanxiety and physiological activation are less likely to benefit from treatment (Lang etal., 1970). Second, research suggests that it is those who show a decrease in their ini-tial reaction to feared stimuli on subsequent sessions (i.e., across-session habituation)that are most responsive to exposure treatment (Foa & Chambless, 1978).

CONCLUSIONS, IMPLICATIONS, AND FUTURE DIRECTIONS

Based upon our critical analysis of the existing VH and CO2 literature, a number ofconclusions are warranted in regard to the psychological factors/processes involvedwith challenge responding. We first discuss the conclusions for the primary method-ological and interpretive issues of this research, and then address the major conclu-sions for the conceptual issues.

Methodological and Interpretative Issues/Conclusions

There are a number of methodological issues specific to research using VH and CO2

that affect interpretations of the existing studies. These methodological issues gener-ally pertain to how the large majority of researchers have measured psychological fac-tors/processes and bodily arousal, the relative frequency of exposure to challenge,and the procedural tactics used.

First, existing VH and CO2 studies rely extensively on self-report measures to assesspsychological factors and processes. Although questionnaires typically are suitable forassessing psychological factors (i.e., thematic content of thought), they are not equallysuitable for assessing psychological processes (Beck & Emery, 1985). Specifically,questionnaires cannot adequately assess process-related issues (i.e., continues types of


cognitive change), particularly when administered only pre-post challenge (Sheehy,Kamon, & Kiser, 1982). For example, although people that differ on the ASI (high vs.low) respond differently to challenge, it is not known how this dispositional differenceemerges on-line during the challenge itself (McNally, 1999). Additionally, question-naires have other limitations such as method-content confounds when they are usedas the sole index of psychological factors (Cone, 1998).

Drawing from the methods of experimental cognitive psychology, researchers havefound that anxiety disorders are characterized by a number of specific types of cogni-tive process abnormalities, particularly interpretative, attentional, and memory biasesfor threatening information (e.g., McNally, 1995). By using these cognitive methodol-ogies in challenge studies, researchers may be in a better position to understand howthese psychological process dimensions (i.e., automatic responses) are produced andmaintained (e.g., Zvolensky, Eifert, Lejuez, & McNeil, 1999). Aside from protectingagainst reporting biases and recall errors, these methodologies also have the advan-tage of being able to be administered on-line. Thus, these methodologies may be par-ticularly helpful in isolating change at the cognitive level of analysis during time peri-ods in which certain processes are most “active” (Eifert et al., 1999).

Second, few serious attempts have been made to understand how anxiety modulatesover time (Lejuez, Zvolensky, & Eifert, 1999). This limitation hinders our understand-ing of the nature of anxiety in that anxiety disorders, by definition, are characterizedby repeated instances of emotional distress. Thus, researchers may erroneously have as-sumed that a single exposure to the provocation agent is sufficient to tap a presumedpsychological disposition related to anxious responding. In a related way, LeDouxand colleagues have emphasized that extinction of a fear response requires the samebiological processes as the acquisition of a fear response (i.e., active learning process;LeDoux, 1995). Thus, by providing more frequent exposure to anxiety-provokingagents, researchers may be in a better position to isolate how anxious and fearful re-sponding is acquired, maintained, and reduced.

Third, few researchers have distinguished between peripheral and central somaticactivity. Research suggests peripheral indices of arousal often are poorly correlatedwith physiological changes (LeDoux, 1995). Thus, perhaps the lack of clear evidencein regard to bodily changes differentiating between groups during panic induction isdue to the lack of direct assessment of central arousal (e.g., EEG). If true, researcherswill help clarify how processes at the psychological and physiological/neuropsychologi-cal levels of analysis intersect by employing more direct assessment of central arousal.

Finally, differences in administration methods and procedures impede precise in-terpretations of the role of psychological factors/processes. Specifically, the extent towhich a variety of methodological variables such as administration procedures (e.g.,single-blind vs. double-blind) and preparations (e.g., gas masks vs. breathing canopy;gas concentration) contribute to different degrees of anxious responding is notknown. Further, these differences may be even more pronounced when different res-piratory provocation methods are employed. For example, Rapee (1995) has sug-gested that there may be a greater degree of control over breathing processes duringVH compared to CO2, partially accounting for the lower rates of panic during VH. Asanother example, the degree of researcher involvement with challenge administra-tion may affect response to challenge; administering CO2 in a single-blind fashionmay be less fear-evoking compared to a double-blind protocol. Researchers will needto directly assess the impact of these issues in order to make more accurate compari-sons across research sites.


Taken together, they key methodological/procedural issues in the existing provoca-tion research naturally restrict our interpretations of the role of psychological variablesin anxious responding. By addressing these methodological issues, it will be possible toshed more light on how information about bodily sensations is processed (McNally,1999). We now turn to the major conclusions regarding the influence of psychologicalprocesses related to anxious and fearful responding during states of bodily arousal.

Conceptual Issues/Conclusions Dealing with Psychological Processes

There are a number of major conclusions from this review that can be offered in termsof explicating the psychological factors/processes involved with anxious responding.

First, although people do not uniformly respond to challenges, the vast majoriy ofclinical and nonclinical individuals do experience anxiety and panic-like symptoms(Eifert et al., 1999). For example, both persons with and without anxiety disorders ex-perience elevated anxiety and arousal in response to VH and CO2 (Forsyth et al.,1999). Both strategies also produce panic in persons with elevated fears of bodilyarousal, physical danger (e.g., suffocation), and other negative expectensies (e.g., go-ing crazy) (Antony et al., 1997). Further, when researchers take into consideration in-terindividual differences in response to challenge, rates of panic attacks are all themore apparent (Forsyth et al., 1999). Thus, it seems reasonable to conclude that VHand CO2 serve as a valid laboratory analogue of anxiety and panic-related responding(Margraf et al., 1986).

Second, consistent with cognitive-behavioral theories of anxiety disorders, bodily sen-sations common to high arousal appear to be necessary, but not necessarily sufficient,for an elevated anxious response (Munjack, Brown, & McDowell, 1993; van der Molenet al., 1986). Indeed, it is primarily when somatic sensations are experienced as person-ally threatening that they will be anxiety-evoking (Clark, 1993; Margraf & Ehlers, 1989).A number of findings support the moderating effects of fear of bodily sensations, in-cluding that persons with and without anxiety disorders respond with heightened anxi-ety to challenge if they dislike and/or fear the potential negative consequences ofarousal (Holloway & McNally, 1987; Merckelbach et al., 1993; Perna et al., 1994). Addi-tionally, experimental manipulations that increase physical threat result in elevated anx-iety (Rapee et al., 1986). As concerns about physical sensations commonly occur in per-sons with PD, blood-injection-injury, situational, natural environment, and height-specific phobias (Craske, Mohlman, Yi, Glover, & Valeri, 1995; van den Hout, van derMolen, Griez, & Lousberg, 1987), these particular types of threat-related concerns likelyaccount, in part, for the lack of differences in challenge response between certain diag-nostic groups (Antony et al., 1997; Craske & Sipsas, 1992).

In a related way, the relative degree of congruity of one’s concerns about the fearedsensations is an important individual difference dimension, such that elevated anxietyis primarily produced when triggered by specific fear cues that are most similar and sa-lient to their fear. For example, the ASI and Suffocation Fear Scale (SFS) that eachmeasure specific concerns about heightened autonomic arousal are better predictorsto VH relative to trait anxiety (Eke & McNally, 1996; McNally & Eke, 1996; Rapee &Medoro, 1994). This finding is consistent with Lang’s (1987) bioinformational theoryof fear responding that suggests individuals will exhibit greater fear to personally rele-vant fear material. A more direct test of this hypothesis could be attained in the futureby matching individuals on personally relevant response elements and evaluating theirresponse to challenge. Such information is important to the continued evaluation of


theoretical accounts of anxious and fearful responding, and perhaps may demon-strate how the challenge paradigm could be used for clinical assessment purposes.

Finally, existing challenge research suggests that controllability, predictability, andsafety signals serve a mediating role between the onset of bodily arousal and anxiousresponding. That is, lower levels of control, prediction, or safety during episodes of so-matic activity increase anxiety, particularly for persons who fear bodily sensations(Carter et al., 1995; Zvolensky, Eifert, Lejuez, & McNeil, 1999). For example, Telch,Silverman, and Schmidt (1996), in a theoretically important study of control over caf-feine challenge, found that the mediational effects of perceived control were appar-ent for individuals who feared anxiety sensations, but not for individuals with littlefear of such sensations. The Telch et al. findings and those of related studies (Zvolen-sky et al., 1998) are consistent with most stress-diathesis conceptualizations of anxietydisorders (e.g., Barlow et al., 1996). Despite the relative degree of consistency in thesefindings, it is important to note that the direction of the relation between perceivedphysical threat, controllability, predictability, and safety has yet to be explicated; spe-cifically, diminished controllability, predictability, and safety may increase physicalthreat levels, vice versa, or some other variable (e.g., disgust, perceived physicalhealth) may account for these results. To more closely examine the relation betweenphysical threat and these other theoretically-relevant psychological process variablesin the future, researchers will need to assess state (e.g., “how threatened do you feel,right now?”) rather than trait physical threat levels. Indeed, trait-like threat measuressuch as the ASI may be not be sensitive enough to tap episodic physical threat changes,particularly when employed in a single session study.

Overall, VH and CO2 are promising paradigms to evoke anxiety and panic respond-ing in clinical and nonclinical populations, although this research is still in an earlystage of development. Contemporary models of anxiety and panic indicate that anx-ious responding is comprised of a heterogenous array of psychological dimensions in-cluding automatic and voluntary processes (e.g., beliefs, attentional biases, memorybiases; Barlow et al., 1996; Mineka & Zinbarg, 1996). In order to explicate the relativeextent to which each of these dimensions may serve as vulnerability factors for anxietypathology, researchers will need to directly examine the processes as well as thematiccontent of psychological variables in the “closed system” of a challenge studies (Mc-Nally, 1999). In this way, the magnitude of the influence of specific psychological pro-cesses can be compared to one another as well as with other vulnerability factors atother levels of analysis (e.g., genetics, developmental events). For example, by study-ing these variables in a simultaneous fashion, it will be possible to better determinehow risk on one dimension (e.g., elevated AS) is affected by risk/non-risk on anotherdimension (e.g., presence or absence of attentional bias) in regard to the emergenceof heightened anxiety and perhaps pathology.

Acknowledgments—This research was supported, in part, from a Sigma Xi Researchgrant awarded to the first author.

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A REVIEW OF PSYCHOLOGICAL FACTORS ...of the factors/processes involved with anxious responding at the psychological level of analysis can be developed and integrated with biological