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To Be Sure, To Be Sure: Intolerance of Uncertainty Mediates

Symptoms of Various Anxiety Disorders and Depression

Peter M. McEvoy

Centre for Clinical Interventions, Perth

University of Western Australia, Perth

Alison E.J. Mahoney

Clinical Research Unit for Anxiety and Depression, Sydney

The Intolerance of Uncertainty Model was initially developed

as an explanation for worry within the context of generalized

anxiety disorder. However, recent research has identified

intolerance of uncertainty (IU) as a possible transdiagnostic

maintaining factor across the anxiety disorders and depres-

sion. The aim of this study was to determine whether IU

mediated the relationship between neuroticism and symptoms

related to various anxiety disorders and depression in a

treatment-seeking sample (N=328). Consistent with previous

research, IU was significantly associated with neuroticism as

well as with symptoms of social phobia, panic disorder and

agoraphobia, obsessive-compulsive disorder, generalized

anxiety disorder, and depression. Moreover, IU explained

unique variance in these symptom measures when controlling

for neuroticism. Mediational analyses showed that IU was a

significant partial mediator between neuroticism and all

symptom measures, even when controlling for symptoms of

other disorders. More specifically, anxiety in anticipation of

future uncertainty (prospective anxiety) partially mediated the

relationship between neuroticism and symptoms of general-

ized anxiety disorder (i.e. worry) and obsessive-compulsive

disorder, whereas inaction in the face of uncertainty

(inhibitory anxiety) partially mediated the relationshipbetween neuroticism and symptoms of social anxiety, panic

disorder and agoraphobia, and depression. Sobel's test

demonstrated that all hypothesized meditational pathways

were associated with significant indirect effects, although the

mediation effect was stronger for worry thanother symptoms.

Potential implications of these findings for the treatment of

anxiety disorders and depression are discussed.

Keywords: intolerance of uncertainty; anxiety; depression;transdiagnostic; mediation

INTOLERANCE OF UNCERTAINTY(IU) has been broadlydefined as cognitive, emotional, and behavioralreactions to uncertainty that bias informationprocessing and lead to faulty appraisals of height-ened threat and reduced coping (Freeston, Rhaume,Letarte, Dugas, & Ladouceur, 1994). The Intoler-ance of Uncertainty Model (IUM) was initiallydeveloped with reference to generalized anxietydisorder (GAD;Dugas, Letarte, Rhaume, Freeston& Ladouceur, 1995; Freeston et al., 1994), which ischaracterized by excessive and uncontrollable worry(American Psychiatric Association, 1994). Morerecently, however, it has been argued that IU mightbe a transdiagnostic mechanism that contributes to

the maintenance of symptoms across anxiety disor-ders and depression (e.g.,Boelen & Reijntjes, 2009;McEvoy & Mahoney, 2011). If IU is demonstratedto be related to multiple internalizing disorders,this would have important implications for thedevelopment of innovative transdiagnostic treatmentprotocols.

The IUM suggests that individuals with GAD finduncertainty distressing, which leads to the commence-ment of worrying when confronted with an uncertainor ambiguous situation (e.g., What if[something bad]

Available online at www.sciencedirect.com

Behavior Therapy 43 (2012) 533545www.elsevier.com/locate/bt

Address correspondence to Peter M. McEvoy, Ph.D., Centre forClinical Interventions, 223 James Street, Northbridge, Perth,Western Australia, 6003; e-mail:[email protected].

0005-7894/43/533-545/$1.00/0 2011 Association for Behavioral and Cognitive Therapies. Published byElsevier Ltd. All rights reserved.
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happens?). The extent to which these individualsbelieve that worrying can be helpful (e.g., worryingwill help to prevent bad things from happening) willthen determine whether they are motivated tocontinue engaging in worrisome thoughts, which, inturn, leads to anxiety. The IUMoutlines twofeedbackloops. The first suggests that anxiety leads to a

negative problem orientation,which is associatedwith thebelief that problemsarethreateningas well aslow problem-solving confidence, which increases theintensity of worry. The second feedback loop suggeststhat anxiety also leads to cognitive avoidance,whereby the individual is motivated to engage inunhelpful strategies such as thought suppression,distraction, and thought replacement. In the shortterm these strategies might be negatively reinforced bya reduction in worrisome thoughts and anxiety.However, they also prevent underlying threat ap-praisals from being modified, which ultimately resultsin more worrisome thoughts, thereby completing the

cycle. The model acknowledges the impact of lifestressors and mood state, and the end point isexhaustion and demoralization (Behar, DiMarco,Hekler, Mohlman, & Staples, 2009).

There is considerable evidence that IU is acognitive vulnerability factor for worry (Koerner& Dugas, 2008; Ladouceur, Gosselin, & Dugas,2000; Sexton, Norton, Walker, & Norton, 2003;van der Heiden et al., 2010) and may be animportant maintaining factor for GAD (Behar et al.,2009; Dugas, Gagnon, Ladouceur, & Freeston,1998). IU is consistently associated with worry(e.g.,Berenbaum, Bredemeier, & Thompson, 2008)and has been found to be a more robust predictorthan several other proposed maintaining factors,including positive metabeliefs, negative problemorientation, cognitive avoidance, perfectionism,perceived control, and intolerance of ambiguity(Buhr & Dugas, 2006; Laugesen, Dugas, &Bukowski, 2003). Experimental studies have alsofound reliable associations between IU and worry(Buhr & Dugas, 2009; Ladouceur, Talbot, &Dugas, 1997; Ladouceur et al., 2000; Rosen &Knuper, 2009). IU has been found to distinguishbetween nonclinical worriers and those with GAD

of varying severity (Dugas et al., 2007; Ladouceur,Blais, Freeston, & Dugas, 1998), and van derHeiden et al. (2010) found that the relationshipbetween neuroticism and symptoms of GAD wasmediated by both IU and negative metacognitionsin a clinical sample with primary GAD. Finally,changes in IU are associated with improvements inworry and anxiety symptoms during cognitive-behavioral therapy (CBT; Dugas & Ladouceur,2000; Dugas et al., 2003). Dugas et al. (2010)compared CBT targeting IU to applied relaxation

and wait-list control for GAD. While both activetreatment conditions were more effective than wait-list control, the CBT condition was most effective,particularly in the longer term. In sum, the evidencethat IU motivates engagement in worry is strong.

Evidence has recently been accumulating that IUis also associated with symptoms of other anxiety

disorders and depression. For instance, IU has beenassociated with symptoms of obsessive-compulsivedisorder (OCD). Tolin, Abramowitz, Brigidi, andFoa (2003)found that IU was higher in compulsivecheckers and repeaters, compared to obsessive-compulsive noncheckers and nonanxious controls,andHolaway, Heimberg, and Coles (2006) foundthat IU was equally associated with symptoms ofGAD and OCD, compared to nonanxious controls.Using a mixed sample of compulsive checkers andnonclinical controls, Lind and Boschen (2009)found that IU fully mediated the relationshipbetween responsibility appraisals and checking

behavior. Importantly, IU has also been found topredict OCD symptoms after controlling for moodand worry (Steketee, Frost, & Cohen, 1998), andDugas, Gosselin, and Ladouceur (2001)found thatOCD symptoms and worry were unique predictorsof IU, when controlling for demographics and panicsymptoms.

An association has also been found between IUand social anxiety. IU has been found to explainunique variance in symptoms of social phobia, evenafter controlling for related constructs such as fear ofnegative evaluation, anxiety sensitivity, positive andnegative affectivity, low self-esteem, worry, andneuroticism (Boelen & Reijntjes, 2009; Carleton,Collimore, & Asmundson, 2010). Carleton et al.found that the degree to which one is paralyzed in theface of uncertainty (i.e., inhibitory anxiety subscaleof the Intolerance of Uncertainty Scale [IUS-IA]) wasrobustly, uniquely, and significantly related to socialanxiety symptoms when controlling for positive andnegative affectivity, fear of negative evaluation, andanxiety sensitivity. Furthermore, IU has been foundto be positively associated with changes in socialanxiety over a subsequent 1-week period (Riskind,Tzur, Williams, Mann, & Shahar, 2007) and a

significant predictor of social comparisons (Butzer &Kuiper, 2006).There is also evidence that IU is related to anxiety

sensitivity (AS), which has been implicated in thedevelopment and maintenance of panic disorderand agoraphobia (PD/A). Carleton, Sharpe, andAsmundson (2007)speculated that the associationbetween AS and IU may result from those withPD/A being intolerant of uncertainty about physicalsymptoms of anxiety. This suggestion implies thatalthough trait IU might be more strongly related to

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GAD, IU is nonetheless relevant to the core fear ineach disorder. In contrast,Dugas, Marchand, andLadouceur (2005)found that symptoms of PD/A,as measured by the Bodily Sensations Question-naire and Agoraphobic Cognitions Questionnaire,were not significantly correlated with IU. Theseresearchers also found that patients with PD/A

endorsed the IUS less strongly than those withGAD. However, a nonclinical control was not usedin this study, so it was not possible to determinewhether the mean IUS score for the PD/A group wasstill elevated. Previous studies using the IUS havefound lower means in nonclinical samples withoutGAD symptoms (e.g.,M =43.8,SD =10.8;Freestonet al., 1994) compared to the patients with PD/A inDugas et al.'s study (M =63.2, SD =20.34), whichsuggests that IU may still be elevated in PD/A.

Sexton et al. (2003) investigated a hierarchicalmodel with neuroticism leading to IU and AS, which,in turn, lead to symptoms of OCD, health anxiety,

panic disorder (Beck Anxiety Inventory [BAI]), andworry. Neuroticism was considered to be a higher-order factor common to all anxiety disorders thatarose from genetic influences and early childhoodlearning, whereas IU and AS were considered to besecond-order and potentially disorder-specific fac-tors. Path analysis showed that in the hypothesizedmodel neuroticism made direct contributions to theprediction of panic symptoms, OCD symptoms, andworry, supporting the theory that neuroticism is aglobal vulnerability factor that directly influencesmultiple anxiety manifestations. Neuroticism alsodirectly influenced AS and IU, which were purportedto be specific vulnerability factors. AS made directcontributions to the prediction of panic symptoms,health anxiety, and OCD symptoms, whereas IUonly made a direct contribution to worry. Thesefindings suggest that IU may be a specific vulnera-bility factor for worry rather than a common factoracross anxiety disorders. However, there are alter-native explanations for this finding and furtherquestions remain to be answered. First, Sexton etal.'s study includeda nonclinical student sample,so itis unclear whether the findings would generalize to aclinical sample with more severe psychopathology.

Second, the sample size was relatively small (N=91),which may have underpowered the analyses to detectimportant effects. Third, symptoms were limited topanic, health anxiety, OCD, and worry, so it isunclear whether IU could contribute to the predictionof symptoms related to other emotional disorderssuch as social phobia and depression.

There is accumulating evidence that IU is alsoassociated with depression, although the relativestrength of this association compared to thatbetween IU and symptoms of other disorders has

been variable. In an undergraduate sample,Dugas,Schwartz, and Francis (2004)found that while IUwas more strongly associated with worry thandepression, both worry and depression explainedunique variance in IU. In an analog sample withvarying degrees of somatic and cognitive GADsymptoms,Buhr and Dugas (2002) found that IU

wasnotmore strongly associated with worry thandepression or anxiety symptoms. Interestingly, de

Jong-Meyer, Beck, and Riede (2009) found that in acommunity sample IU was more strongly correlatedwith depression than anxiety symptoms, and that IUcontinued to be significantly associated with de-pression when controlling for metacognitive beliefs.In a dysphoric sample included in the same study,however, although IU was significantly correlatedwith depression symptoms, it did not explain uniquevariance above and beyond metacognitive beliefs.Importantly, van der Heiden et al. (2010) found thatthe relationship between neuroticism and depres-

sion symptoms was mediated by both IU andnegative metacognitions in a clinical sample. Thus,IU appears to be associated with depressionsymptoms, although the strength of this associationrelative to other symptoms and cognitive constructshas varied across studies.

In sum, IU appears to be associated with a broadarray of anxiety and depressive disorders and thusmay represent an important transdiagnostic main-taining factor (Starcevic & Berle, 2006). However,there are several limitations of existing studies.First, most studies have used nonclinical samples,bringing into question the generalizability of thefindings to treatment-seeking individuals withvarious anxiety and depressive disorders. Second,some studies focus on the relative strength ofendorsement of IU across diagnostic or analoggroups (i.e., compare group means), rather thanexamining the relative contribution of IU to symp-toms across disorder-related symptoms or testingmeditational models. Although individuals withGAD might endorse measures of IU more stronglythan other disorder groups, IU may nonetheless be animportant contributor to symptoms of other disor-ders. Third, many studies have examined IU within

the context of a single diagnostic group or withdiagnosis-specific symptom measures, which pre-cludesexamination of IU as a transdiagnosticprocess.This study sought to address these limitations byusing a large mixed-diagnosis clinical sample to testwhether IU mediates the relationship between neu-roticism andsymptoms of GAD, PD/A, social phobia,OCD, and depression. Moreover, recent research hassuggested that different aspects of IU are associatedwith symptoms of different anxiety and depressivedisorders, so this study also sought to examine

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whether these differences extended to mediationeffects between neuroticism and symptoms.

Specifically, Carleton, Norton, and Asmundson(2007) found that a 12-item version of the IUS(Freeston et al.,1994) providedthe best fit tothe datafrom two undergraduate samples, and that the totalscore correlated with worry, symptoms of GAD,

depression, and anxiety. This version of the IUS iscomprised of two subscales, namely, prospectiveanxiety (IUS-PA) and inhibitory anxiety (IUS-IA).Prospective anxiety relates to fear and anxiety inanticipation of uncertainty, whereas inhibitoryanxiety relates to inaction in the face of uncertainty.A recent study with a treatment-seeking samplefound that the IUS was significantly associated withdiagnosis-related symptoms for PD/A, social phobia,OCD, GAD, and depression, even when controllingfor all other symptom measures and neuroticism(McEvoy & Mahoney, 2011). Moreover, the IUS-PAwas uniquely associated with symptoms of GAD and

OCD, whereas the IUS-IA was uniquely associatedwith symptoms relating to the phobic disorders(social phobia, PD/A) and depression. The only otherstudy using this version of the IUS in a clinical samplealso found that inhibitory anxiety, but not prospec-tive anxiety, was uniquely associated with socialanxiety symptoms (Carleton et al., 2010). Together,these findings suggest that individuals with GAD andOCD particularly fear future uncertainty, which isconsistent with the fact that worry and obsessions areoften future oriented (i.e., anticipatory). In contrast,those with phobic disorders and depression aremore paralyzed in the face of uncertainty, which isconsistent with the fact that phobic disorders anddepression are associated with inaction and with-drawal (i.e., inhibition). Thus, IU was found to be atransdiagnostic phenomenon, although differentaspects of IU were related to different symptoms ofinternalizing disorders.

This study sought to extend these findings bytesting whether IU mediates the relationship be-tween the general vulnerability factor of neuroti-cism and symptoms of various anxiety disordersand depression. Guided by the findings ofMcEvoyand Mahoney (2011) and Carleton et al. (2010), it

was hypothesized that the IUS-PA would mediatethe relationship between neuroticism and symp-toms of GAD and OCD. It was further expectedthat the IUS-IA would mediate the relationshipbetween neuroticism and symptoms of socialanxiety, PD/A, and depression.

Method

participants

Participants (N=328, 54% women) were referredto a specialist anxiety disorders treatment service by

general practitioners or psychiatrists. At the initialassessment participants completed the standardquestionnaire battery and were diagnosed via asemistructured clinical interview with a consultantpsychiatrist. Diagnoses from the Composite Inter-national Diagnostic InterviewAuto (CIDI-Auto;World Health Organization, 1997) were available

for 106 of the participants to provide an indicationof the frequency of anxiety and affective disorders.The proportions of these patients meeting criteriafor each diagnosis were panic disorder with orwithout agoraphobia (PD/A)=52%, GAD=50%,social phobia= 45%, specific phobia= 27%,OCD=21%, PTSD=7%, major depressive disor-der (MDD) = 43%, bipolar disorder= 4%, anddysthymic disorder= 11%. The mean number ofdiagnoses was 3.2 (SD =1.96), with 76% havingtwo or more diagnoses, 59% with three or more,and 42% having four or more. Considering thosewith the disorders most closely related to the five

symptom measures in this study (social phobia,GAD, PD/A, OCD, MDD), the most commoncomorbid disorder for those with social phobia wasGAD (74%), followed by PD/A (67%), MDD(48%), and OCD (23%). For PD/A, the mostcommon comorbid diagnosis was GAD (52%),followed by social phobia (51%), MDD (47%),and OCD (26%). For GAD the most commoncomorbid disorder was social phobia (67%),followed by PD/A (62%), MDD (44%), and OCD(27%). For OCD the most common comorbiddiagnosis was PD/A (74%), followed by GAD(63%), social phobia (47%), and MDD (42%).Finally, the most common comorbid diagnosis forMDD was PD/A (67%), followed by GAD (51%),social phobia (50%), and OCD (24%). Mean agewas 34.1 years (SD =11.76). Twenty-three percentof the sample had completed high school, 32%were married or in de facto relationships, 59%never married, and 9% were separated or divorced.

measures

Composite International DiagnosticInterviewAuto

The CIDI-Auto was used to assess the presence ofanxiety and depressive disorders in the currentsample. The CIDI-Auto is a computerized, self-reported, structured diagnostic interview for mentaldisorders according to International Classificationof Diseases (ICD-10;World Health Organization,1993) and the DSM-IV (American PsychiatricAssociation, 1994). It has demonstrated proceduralvalidity against expert clinical diagnoses (Peters &Andrews, 1995) and has good reliability (Andrews& Peters, 1998; Wittchen, 1994).


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Intolerance of Uncertainty ScaleThe original English version of the IUS (Buhr &Dugas, 2002) is composed of 27 items and measuresnegative beliefs about and reactions to uncertainty(e.g., Uncertainty makes life intolerable). Internalconsistency (= .94) and testretest reliability (r =.74over 5 weeks) are good (Buhr & Dugas, 2002).

Evidence of discriminant, convergent, content, andcriterion validity have been reported in multiplepopulations (Buhr & Dugas, 2002, 2006; Carleton,Norton, et al., 2007; Norton, 2005). The 12-itemversion has been found to be highly correlated(r =.96) with the full version in two studies withboth undergraduate (Carleton, Norton, et al.,2007) and clinical samples (McEvoy & Mahoney,2011), and is comprised of two subscales: IUS-PAand IUS-IA. The IUS-PA measures anxiety inanticipation of uncertainty (e.g., I always wantto know what the future has in store for me),whereas the IUS-IA measures inhibition of action or

experience (e.g., When it's time to act, uncertaintyparalyzes me).

Penn State Worry QuestionnaireThe Penn State Worry Questionnaire (PSWQ;Meyer, Miller, Metzger & Borkovec, 1990) i s awidely used 16-item measure of worry with excellentinternal consistency (=.86 .95) and goodtemporal stability (r =.92 over 8 to 10 weeks andr =.74 .93 over4 weeks; Meyer et al., 1990; Molina& Borkovec, 1994). The measure has demonstratedevidence of construct validity in clinical and com-munitypopulations (e.g., Brown, Antony, & Barlow,

1992; van Rijsoort, Emmelkamp, & Vervaeke,1999).

Body Sensations Questionnaire and AgoraphobicCognitions QuestionnaireThe Body Sensations Questionnaire (BSQ) and theAgoraphobic Cognitions Questionnaire (ACQ;Chambless, Caputo, Bright, & Gallagher, 1984)are established self-report measures of symptomsassociated with PD/A. The scales measure thephysical sensations and thoughts respondentstypically experience when they are nervous orfrightened. Internal consistency (=.80 and .87

for ACQ and BSQ, respectively) is good, andevidence of temporal stability and construct validityhave been well provided (see Chambless, Beck,Gracely, & Grisham, 2000; Chambless & Gracely,1989; Chambless et al., 1984).

Beck Depression InventoryIIThe Beck Depression InventoryII (BDI-II; Beck,Steer, & Brown, 1996) is a 21-item measure of theseverity of depression symptoms experienced duringthe previous fortnight. Internal consistency (=.92)

and testretest reliability (r =.93 over 1 week) areestablished (Beck et al., 1996), and evidence forconstruct validity has been demonstrated (e.g.,Dozois, Dobson, & Ahnberg, 1998; Osman, Kopper,Barrios, Gutierrez, & Bagge, 2004).

Social Phobia Scale and Social Interaction Anxiety

ScaleThe Social Phobia Scale (SPS) and the SocialInteraction Anxiety Scale (SIAS;Mattick & Clarke,1998) are widely used, 20-item measures ofperformance and interaction anxiety, respectively.The SPS describes situations in which the person isthe focus of attention and observed by others, suchas eating, drinking, and writing. The SIAS containsitems reflecting cognitive, affective, and behavioralreactions to interactional situations, such as ner-vousness when speaking to authority, mixing withpeople, and talking to an attractive person of theopposite sex. The 5-point response scale for both

scales is not at all, slightly, moderately, very, orextremelycharacteristic of me. Internal reliabilitiesfor the SPS (=.89) and SIAS (=.93) are highwithin clinical samples and these scales have beenshown to be sensitive to change (Cox, Ross,Swinson, & Direnfeld, 1998; Mattick, Peters, &Clarke, 1989).

Eysenck Personality QuestionnaireNeuroticismSubscaleThe 23-item neuroticism subscale of the EysenckPersonality Questionnaire (EPQ-N; Eysenck &Eysenck, 1975) was used in the current study.Data demonstrating reliability and validity of theEPQ-N are extensive (e.g., see Barrett, Petrides,Eysenck, & Eysenck, 1998; Caruso, Witkiewitz,Belcourt-Dittloff, & Gottlieb, 2001).

Padua InventoryWashington State UniversityRevisionThePadua InventoryWashington State UniversityRevision(PI;Burns, 1995) is a widely used 39-itemself-report measure of OCD symptoms. Each item(e.g., I feel my hands are dirty when I touchmoney) is rated on a 5-point scale according to thedegree of disturbance caused by the thought orbehavior from 0 (not at all) to 4 (very much).Although subscale scores are available, the totalscore was used in the current study. Evidence ofconstruct, convergent, and discriminant validity hasbeen demonstrated (Burns, Keortge, Formea, &Sternberger, 1996; Jnsdttir & Smri, 2000).

procedure

Patients referred to a specialist anxiety disordersclinic completed a standard battery of question-naires during their initial assessment, including the


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PSWQ, .14, 95% CI [.09.21]; PI, .05, 95% CI[.02.10]; BSQ/ACQ, .04, 95% CI [.01.07];SPS/SIAS, .10, 95% CI [.05.16]; and BDI, .06,95% CI [.03.11]. In these models the indirecteffect for the PSWQ was only significantly strongerthan that for the BSQ/ACQ, but not the othersymptom measures. As a final conservative test theindirect effects were calculated again controlling forall symptom measures and effects remained statis-tically significant for the PSWQ, .09, 95% CI[.04.14]; PI, .02, 95% CI [.0001.06]; BSQ/ACQ,.02, 95% CI [.003.05]; SPS/SIAS, .05, 95% CI[.01.10]; and BDI, .09, 95% CI [.05.14]. In these

models no indirect effect was significantly strongerthan any other.

DiscussionIU has traditionally been examined within thecontext of GAD and worry. However, recentresearch suggests that IU may be an importantcontributor to symptoms across the anxiety disordersand depression. This is the first study to examinewhether IU mediated the relationship betweenneuroticism and symptoms of social phobia, PD/A,GAD, OCD, and depression in a single treatment-seeking clinical sample. Moreover, this study sought

EPQ-N

Inhibitory

Anxiety

PSWQ

.49*

.49*

Prospective

AnxietyPIsqrt

ACQ/BSQ

SPS/SIAS

BDI-II

.39*

.28*

.34*

.34* (.51*)

.21* (.40*)

.23* (.36*)

.27* (.38*)

.38* (.56*)

.36*

.23*

FIGURE 1 Meditational model. Mediational pathways are bolded, whereas direct effects of neuroticism on symptoms are not. Beta

coefficients in parentheses are direct effects of neuroticism on the respective symptom measure, prior to controlling for the mediator.

BSQ= Bodily Sensations Questionnaire, ACQ = Agoraphobic Cognitions Questionnaire, PSWQ = Penn State Worry Questionnaire,

SIAS=Social Interaction Anxiety Scale, SPS=Social Phobia Scale, PIsqrt=Padua Inventory square root, BDI-II=Beck Depression InventoryII,

EPQ-N= Eysenck Personality Questionnaire Neuroticism subscale. * pb .001

Table 4

Sobel's Test of Mediation Effects

Criterion Indirect Effect SE Z StandardizedIndirect Effect

95% CI % of Variancea

[LL, UL]

PSWQ .58 .10 5.81** .18 [.12, .24] 20%

PIsqrt .07 .02 3.64* .03 [.01, .05] 9%

BSQ/ACQ .46 .10 4.36** .04 [.02, .05] 9%

SPS/SIAS .96 .17 5.79** .05 [.04, .07] 13%

BDI-II .59 .11 5.49** .05 [.03, .07] 17%

Note. BSQ=Bodily Sensations Questionnaire, ACQ=Agoraphobic Cognitions Questionnaire, PSWQ=Penn State Worry Questionnaire,

SPS= Social Phobia Scale, SIAS= Social Interaction Anxiety Scale, PIsqrt= Padua Inventory square root, BDI-II= Beck Depression

Inventory. CI= Confidence Interval, LL= Lower Limit, UL= Upper Limit.a Percent of variance in the criterion variable explained by the indirect effect. * pb .01, **pb .001.


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to determine whether two aspects of IU, namelyprospective and inhibitory anxiety, would mediatedifferent disorder-related symptoms.

The hypothesis that IU would mediate therelationship between neuroticism and symptomsof GAD (PSWQ) and OCD (PIsqrt) was partiallysupported, with prospective anxiety partially me-

diating this relationship, explaining 20% and 9%of the variance in these measures, respectively.Likewise, the hypothesis that IU would mediate therelationship between neuroticism and symptoms ofsocial phobia (SPS/SIAS), PD/A (BSQ/ACQ), anddepression (BDI-II) was also supported, with inhib-itory anxiety partially mediating this relationship,explaining, 13%, 9%, and 17% of the variance inthese measures, respectively. The magnitude of theindirect effects reduced somewhat when controllingfor other symptom measures, suggesting that theindirect effects could be partially accounted for bythe covariance in symptom measures. Importantly,

however, the indirect effects remained statisticallysignificant, even when controlling for all othersymptom measures. This finding suggests that thepartial mediation effects across the disorder-relatedsymptom measures could not be fully explained bycomorbid symptoms.

It is noteworthy that IU was a significantlystronger mediator for worry than the other symp-toms. A substantial body of previous research hasfound a strong and robust relationship between IUand worry and this was replicated here. Our findingis consistent with IU being more important in themaintenance of worry than some of the coresymptoms of other anxiety disorders and depressionthat were measured in this study. An alternativeexplanation for this finding is that IU, being acognitive construct, is more strongly related to worrybecause it is a cognitive symptom, compared tomeasures such as the BSQ, which measures physicalsymptoms of anxiety. However, the ACQ and PI alsomeasure cognitive constructs related to agoraphobiaand OCD, respectively. Yet another alternative isthat IU is most strongly associated with the PSWQbecause both constructs are strongly related to theunderlying cognitive construct of repetitive negative

thinking (RNT) in particular. There is considerableevidence that constructs tapping into RNT, such asworry, rumination, and postevent processing, sharemany qualities (Ehring & Watkins, 2008; McEvoy,Mahoney, & Moulds, 2010), despite them beingexamined almost exclusively within the anxiety,depression, and social phobia literatures, respective-ly. Indeed, it has been argued that these constructsmay be more similar than different, with temporalorientation (i.e., future vs. past focus) being the onlyreplicated difference (Ehring & Watkins, 2008), and

therefore that RNT is a transdiagnostic cognitiveconstruct (Harvey, Watkins, Mansell, & Shafran,2004). While the relationship between IU and worryhas been well documented, the relationships betweenIU and other forms of RNT require furtherinvestigation, especially in diagnostically heteroge-neous samples. If IU is strongly related to the

underlying construct of RNT, then it may be morestrongly associated with worry, depressive rumina-tion, and postevent processing, compared to otherphysical, emotional, behavioral, and even cognitivesymptoms, irrespective of diagnosis. Future researchcould examine this possibility by testing whether IUmediates the relationship between neuroticism andvarious measures of RNT to a similar degree.Furthermore, if IU leads to RNT, then RNT maymediate the relationship between IU and othersymptoms of anxiety and depressive disorders.Taken together, such findings would argue that IUis a relatively specific vulnerability factor for RNT,

rather than necessarily being particular to GAD.Consistent with this possibility, Yook, Kim, Suh, andLee (2010)found that IU was correlated with bothworry and depressive rumination in a clinical samplewith MDD and/or GAD. Furthermore, meditationalanalyses showed that worry partially mediated therelationship between IU and anxiety symptoms, andrumination fully mediated the relationship betweenIU and depression.

Despite the fact that in this study IU mediated therelationship between neuroticism and worry moststrongly, IU also significantly mediated this relation-ship for all other symptom measures. These resultsare consistent with previous research finding signif-icant associations with symptoms related to panicdisorder (Carleton, Sharpe, et al., 2007; Dugas et al.,2001), social phobia (Boelen & Reijntjes, 2009;Carleton et al., 2010; Riskind et al., 2007), OCD(Holaway et al., 2006; Lind & Boschen, 2009; Tolinet al., 2003), and depression (de Jong-Meyer et al.,2009; Dugas et al., 2004; van der Heiden et al.,2010). Importantly, some of these previous studieshave found that IU is uniquely associated withsymptom measures even after controlling for otherfactors theoretically posited to also contribute to

symptoms, such as metacognitions, cognitive avoid-ance, negative problem orientation, fear of negativeevaluation, perfectionism, responsibility appraisals,anxiety sensitivity, positive and negative affectivity,self-esteem, and other symptom measures. Notwith-standing these findings, it is important for futurestudies to examine the degree to which IU explainsunique variance in symptoms across the internalizingdisorders, above and beyond other maintainingfactors articulated in diagnosis-specific and indeedtransdiagnostic models. For instance, it may be that


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the variance explained by IU in the BSQ and ACQhere is better explained by a combination of otherconstructs in well-established models of panicdisorder, such as anxiety sensitivity, catastrophicmisinterpretations of physical sensations, copingself-efficacy, avoidance, and the use of safety-seekingbehaviors (e.g., Casey, Oei, & Newcombe, 2004;

Clark, 1986).Another avenue for future research is to investi-

gate IU in relation to areas of core concern acrossdiagnoses, rather than as a trait variable.Carleton,Sharpe, et al. (2007)speculated that the associationbetween anxiety sensitivity and IU may be anintolerance of uncertainty regarding the meaning ofphysical symptoms of anxiety. For instance, it maybe that individuals with PD/A are particularlyintolerant of the possibility that an increase intheir heart rate might signal an impending heartattack, and that this specific vulnerability might bemore strongly related to panic symptoms than trait

IU. Likewise, an individual with social phobia maybe particularly intolerant of uncertainty aboutpotential social catastrophes. If IU were assessedin relation to diagnosis-specific fears, then theassociations may be stronger than those found inthis study.

In contrast to our findings, several studies havefound evidence against a strong unique associationbetween panic disorder symptoms and the IUS. In asample with noncomorbid panic disorder, Dugaset al. (2005) found that IU was not significantlyassociated with the same measures of panicsymptoms that were used in this study. Likewise,de Jong-Meyer et al. (2009) found that IU andmetacognitions were associated with worry butnot with panic sensations, as measured by the BAI.The BAI is predominantly a measure of somaticsymptoms of anxiety that has been found to bemore strongly related to panic disorder than otheranxiety disorders (Cox, Cohen, Direnfeld, &Swinson, 1996). Consistent with our findings,Sexton et al. (2003) found that IU mediated therelationship between neuroticism and worry andthat neuroticism had a direct relationship withOCD, panic, and worry. In contrast to our findings,

however, IU did not mediate the relationship foreither OCD or panic symptoms.There are a few potential explanations for the

discrepancy between these findings and our results.First,Dugas et al.'s (2005), de Jong-Meyer et al.'s(2009), and Sexton et al.'s (2003) studies hadsubstantially smaller sample sizes (N=45, 71, and91, respectively), thus having considerably lesspower to detect true associations than the currentstudy did (n =319). Second, having a larger samplemay have reduced the influence of range attenua-

tion effects on the strength of associations. Third,our sample was highly comorbid, which may haveresulted in us identifying associations not found inDugas et al.'s diagnostically pure sample. It isarguable that the high level of comorbidity in oursample is more typical of real-world clinics and thusour findings more generalizable to clinical popula-

tions. de Jong-Meyer et al.'s sample comprised ofdysphoric individuals recruited by advertisementsand no diagnostic information was reported, andSexton et al. used an unselected sample of under-graduate students. Fourth, rather than using a totalscore, we examined the relationship betweendifferent aspects of IU and symptoms (prospectiveand inhibitory anxiety), which may have increasedour chances of detecting an effect. Thus, it appearsthat in large, comorbid treatment-seeking samples,IU may be more strongly related to a broader arrayof symptoms. However, it is possible that if we hadincluded a measure of AS in our model, IU would

no longer mediate the relationship between neurot-icism and panic symptoms.

There are several limitations to this study that mustbe considered. First, the mediation effect through IUexplained a relatively small proportion of variance inall symptom measures. Therefore, although IUshould be targeted in treatment when indicated,IU is likely to be only one of many importantmaintaining factors. Future research should include abroader array of proposed maintaining factors tobetter understand the relative contribution of, andinteractions with, IU across emotional disorders.Second, given that this data was cross-sectional, nocausal conclusions can be made. However, experi-mental research demonstrating that IU reliablycontributes to worry increases our confidence in thepossibility of a causal relationship (Buhr & Dugas,2009; Ladouceur et al., 1997, 2000; Rosen &Knuper, 2009). It is important for future experi-mental and intervention studies to demonstrate thatIU exacerbates symptoms, and that increasingtolerance for uncertainty ameliorates symptoms,across emotional disorders. It is also likely that therelationship between IU and symptoms is reciprocal,which is another avenue for future empirical

evaluation. Third, structured diagnostic assessmentswere not completed by all participants, which mayhave resulted in the inclusion of individuals who didnot meet criteria for an anxiety or depressivedisorder. However, given the high level of symptomsand comorbidityin the subsample that completed theCIDI-Auto, it is likely that almost all participantswould have met criteria for at least one disorder.

Notwithstanding these limitations, the findingsof this study have several important theoretical andtreatment implications. First, IU is emerging as a


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probable transdiagnostic maintaining factor forsymptoms of various anxiety and depressive disor-ders. While our findings provide support for the IUMas it relates to GAD, this model may also provideexplanatory power for other disorders. As such,existing diagnosis-specific and transdiagnosticmodels of internalizing disorders may need to more

clearly articulate how IU interacts with otherproposed maintaining mechanisms. Second, ourfindings provide some indication of the relativecontribution of IU across the disorders, which couldfacilitate treatment matching. For instance, CBT withthe goal of increasing tolerance of uncertainty shouldbe a core feature of treatments for GAD (e.g., seeDugas et al., 2010; Ladouceur et al., 2000). Likewise,our results suggest that IU should be targeted intreatments for all other anxiety disorders anddepression, although it may occupy a smallerproportion of therapeutic time. It is important torecognize that worry can be a feature of any

internalizing disorder and that, as in the presentsample, the diagnosis of GAD is common intreatment-seeking populations. Thus, clinicianswould be well served to fully assess IU in anyindividual presenting with elevated levels of worry,andconsider includingit as an importantmaintainingmechanism in the case formulation. Future researchinvestigating the relationship between IU and otherforms of RNT (e.g., depressive rumination, posteventprocessing) would be informative. A recently devel-oped transdiagnostic measure of RNT (McEvoyet al., 2010) that was demonstrated to have uniqueassociations with a broad array of emotions (anxiety,depression, anger, shame, general distress) may beuseful to further investigate transdiagnostic relation-ships between RNT and IU.

Finally, treatment may also be informed by thefinding that intolerance of prospective uncertaintypartially mediated the relationship between neurot-icism and symptoms associated with GAD andOCD, whereas inhibition in the face of uncertaintypartially mediated this relationship for symptoms ofsocial anxiety, PD/A, and depression. Specifically, itmight be most important to increase tolerance tofuture uncertainty for GAD and OCD, perhaps

with strategies such as focusing attention on thehere and nowrather than future-oriented worry,with the explicit intention to accept and exposeoneself to future unpredictability (e.g., take a waitand see approach). In contrast, the focus for thephobic disorders and depression might be on actionin the face of uncertainty, by reducing actions thatprevent exposure to uncertainty (e.g., ceasing theuse of avoidance and safety-seeking behaviors) andactively engaging in actions that directly confrontuncertainty (e.g., increasing engagement in sponta-

neous activities). Such strategies, in conjunctionwith a rationale for increasing tolerance of uncer-tainty, could be easily incorporated into existingCBT protocols.

Evidence that IU is a transdiagnostic maintainingfactor is accumulating. Consistent with this body ofresearch, our study demonstrated that different

aspects of IU mediated the relationship betweenneuroticism and a broad array of disorder-relatedsymptoms in a treatment-seeking sample. Futureresearch simultaneously testing multiple theoreticallyprescribed mediators across the internalizing disor-ders would be useful to identify the relativecontributions of each one to various manifestationsof psychopathology. If IU continues to explainunique variance in symptoms across the anxietyand depressive disorders in such models, it would beconfirmed as a robust transdiagnostic maintainingfactor. It is conceivable that, together with researchon other transdiagnostic mechanisms, these findings

could guide the development of a transdiagnostictreatment protocol that efficiently and effectivelyimpacts on symptoms of primary and comorbidconditions.

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