Exposure Therapy for Anxiety Disorders: From Fear Reduction to Fear Enhancement

Exposure Therapy for Anxiety Disorders: From Fear

Reduction to Fear EnhancementMichelle G. Craske, Ph.D.

July, 2012Professor of Psychology

Professor of Psychiatry and Biobehavioral SciencesDirector, UCLA Anxiety Disorders Research Center

UCLA

Exposure TherapyExposure Therapy• Repeated, systematic exposure to feared

stimuli

– In vivo – situations, objects, places, people– Interoceptive – sensations– Imaginal – images and memories

Exposure TherapyExposure Therapy• Exposure-based therapies, with or without

adjunctive coping skills, highly effective for anxiety disorders (e.g., Norton & Price, 2007; Hofmann & Smits, 2008)– Panic disorder/Agoraphobia– Obsessive compulsive disorder– Social anxiety disorder– Specific phobias– Generalized anxiety disorder– Posttraumatic stress disorder

Exposure-Based TherapiesExposure-Based Therapies• However:

– Treatment refusal• ??30% (Issakidis & Andrews, 2004)

– Attrition • 15-30% (Haby et al., 2006)

– Limited-response rates• Non-response rates average 40% to 50% (Loerinc et al., in

submission)

– Fear returns• 19-62% experience return of fear (Craske & Mystkowski,

2006)

• What are the mechanisms of exposure therapy for fears and anxiety disorders?

• How can exposure-based learning be optimized?– To enhance response rate and reduce

relapse rate

QUESTIONSQUESTIONS

RECIPROCAL INHIBITIONRECIPROCAL INHIBITION• Systematic desensitization (Wolpe, 1959)

– relaxation as a counter-conditioner of anxiety

– minimal level of fear responding during SD critical to learning process and outcome

• But; – SD equally effective without relaxation (e.g., McGlynn et al.,

1978)

– Exposure therapy equally effective without coping skills (Norton & Price, 2007; Longmore & Worrell, 2006)

– Flooding therapy, involving high arousal, as effective as graduated exposure (e.g., Foa et al., 2005; Miller, 2002)

EMOTIONAL PROCESSING THEORYEMOTIONAL PROCESSING THEORY (Foa & Kozak, 1986; Foa & McNally, 1996)

Fear Structure

Stimulus Response

Threat Meaning

Within sessionHabituation of fear

Between sessionHabituation of fear

Neutral Meaning

FEAR REDUCTION FEAR REDUCTION

• “Stay in the situation until fear subsides”

• Is fear reduction predictive of outcome?

FEAR REDUCTIONFEAR REDUCTION

• Subjective and physiological responding typically declines across exposure trials

• But, poor predictor of outcome– Regression models (Kozak et al., 1988; Pitman et al.,

1996a,b; Baker et al., 2010; Kircanski et al., 2012; Culver et al., 2012)

– Experimental paradigms: overlearning (Farchione & Craske, 2002)

Within session habituation: Contaminant anxiety (Kircanski, Mystkowski, Mortazavi, Baker & Craske, 2012, J Beh Th & Exp Psych)

FEAR REDUCTION

• Subjective and physiological responding typically declines across exposure trials

• But, poor predictor of outcome– Regression models (Kozak et al., 1988; Pitman et al., 1996a,b;

Baker et al., 2010; Kircanski et al., 2012; Culver et al., 2012)

– Experimental paradigms: overlearning (Farchione & Craske, 2002)

Spider FearsPreBAT

Exposure Trials3 min, 1 min ITIFear < 10 (4.3)*

Overlearning200% more (10.7)*

ControlNo more*

PostBAT

3-week Follow-UpBAT

Farchione & Craske, 2002

FEAR EXPRESSION VS FEAR LEARNINGFEAR EXPRESSION VS FEAR LEARNING

• Expression of fear during or at the end of exposure is not a good marker of learning, as assessed at a later point in time (Craske et al., 2008; Craske et al., 2012)


• Memory research (non-emotional):

– Performance during instruction not a reliable index of learning

– Learning occurs without change in performance and vice versa (Bjork & Bjork, 2006)


• Extinction learning (emotional):

– Fear reduction during or at end of extinction training does not predict responding upon re-test (Bouton et al., 2006; Rescorla, 2006; Plendl, Wolfgang et al., 2010)

Mechanisms of Extinction LearningMechanisms of Extinction Learning

• Habituation not a central mechanism underlying extinction (Davis, 2000)

• Formation of inhibitory associations: – the original CS-US association learned during fear

conditioning is not erased during extinction, but rather is left intact alongside secondary inhibitory learning about the CS-US association (e.g., Bouton & King, 1983; Bouton, 1993)

PRE-EXPOSURE-------EXPOSURE--------------------------------------------POST-EXPOSURE

Excitatory Threat

Expectancy

Inhibitory Nonthreat

Expectancy

?

Time ContextNew

AdverseEvents

Retrieval Cues

No Fear Fear

Habituation not a central mechanism

Mismatch with expectancy for adverse events

Neural inhibitory regulation: vmPFC over amygdala

In tact

INHIBITORY LEARNINGINHIBITORY LEARNING

• How can inhibitory learning be maximized during exposure therapy?

• How can inhibitory learning be maximally retrieved at a later point in time, after completion of exposure therapy?

ANXIETY DISORDERS: DEFICITS IN INHIBITIONANXIETY DISORDERS: DEFICITS IN INHIBITION

• Anxiety disorders characterized by

– elevated excitatory learning (CS+) (Lissek et al., 2005; Craske et al., 2008)

• Amygdala (Milad, 2007, 2009)

– deficits in inhibitory learning (CS- and extinction) (Lissek et al., 2005; Craske et al., 2008; Liao & Craske, in press)

• vmPFC (Milad, 2007, 2009)

– deficits in safety learning (Craske et al., 2009; Craske et al., in press)

Craske, Waters, Bergman et al., 2008Craske, Waters, Bergman et al., 2008Behavior Research & TherapyBehavior Research & Therapy

Control High Risk Anxious

Child No diagnosesN = 15

No diagnosesN = 13

Anxiety diagnosesN = 24

Mother/Father

Nodiagnoses

Anxiety diagnoses

Mixed group

Method

• Acquisition phase:– 16 trials:

• 8 CS+ (geometric shape paired with 107db tone)• 8 CS- (alternate shape presented alone)

0 s 7 s 8 s

ToneCS+

CS-

16 trials8 CS+ (UCS),

8 CS-8 trials

4 CS +, 4 CS-8 trials

4 CS +, 4 CS-

acquisition extinction 1 week spontaneousrecovery

Craske, Waters, Bergman et al., 2008Craske, Waters, Bergman et al., 2008Behavior Research & TherapyBehavior Research & Therapy

Conditioning: F(1, 110) = 7.88, p < .001, β = -.15Extinction: F(1, 55) = 6.19, p = .003, β = -.10Extinction retest: F(1, 50) = 9.54, p = .003, β = -.09

ANXIETY DISORDERS: DEFICITS IN INHIBITIONANXIETY DISORDERS: DEFICITS IN INHIBITION

• Anxiety disorders characterized by

– elevated excitatory learning (CS+) (Lissek et al., 2005; Craske et al., 2008)

• Amygdala (Milad, 2007, 2009)

– deficits in inhibitory learning (CS- and extinction) (Lissek et al., 2005; Craske et al., 2008; Liao & Craske, in press)

• vmPFC (Milad, 2007, 2009)

– deficits in safety learning (Craske et al., 2009; Craske et al., in press)

Craske et al., 2009, 2012Craske et al., 2009, 2012

8 baseline trials 8 context trials 8 baseline trials 8 context trials

15 45

+

5 35

0 55 0 55 0 55 0 55 0 55 0 55 0 55 0 55

+

15 45 5 35

+

15 455 35 15 45 5 35

+ + +++ + + + + ++

+

+

Stimulation

Safe – Danger Phases

SAFE – NO CONTRACTION WILL BE GIVEN

DANGER – CONTRACTION MAY BE GIVEN

Count down

Craske, Waters et al. (2009). Biological Psychiatry

2.5

3

3.5

4

4.5

51

to 4

5 to

8

1 to

4

5 to

8

Dis

tal

Pro

xim

al

Dis

tal

Pro

xim

al

Dis

tal

Pro

xim

al

Dis

tal

Pro

xim

al

1 to

4

5 to

8

1 to

4

5 to

8

Baseline Context Safe Threat Safe Threat Baseline Context

Pre-contraction Post-contraction

Contextual Threat Explicit Threat Contextual Threat

EMG

mag

nitu

de [l

n]

Low

Medium

High

Before Contraction After Contraction

Prediction of Onset of Anxiety Disorders: Safe/Danger SR InterceptsCraske et al., 2012 J of Abnormal Psychology

Effects for ADs above and beyond covarying N, UDD, danger

p<.05

INHIBITORY LEARNING IN EXPOSURE THERAPYINHIBITORY LEARNING IN EXPOSURE THERAPY

• How can inhibitory learning be maximized during exposure therapy

• How can inhibitory learning be maximally retrieved at a later point in time, after completion of exposure therapy

• Especially for individuals with anxiety disorders who have deficits in inhibitory learning

Not erasure of fear memory-reconsolidation

Craske et al., 2008; Craske et al., 2012

Culver, Vervliet, & Craske, in submissionCulver, Vervliet, & Craske, in submission

• Mismatch between expectancy of adverse event and its absence of occurrence (Rescorla & Wagner, 1974)

• Deepened extinction – mismatch between expectancy and outcome for more than one stimulus (Rescorla, 2006)– Exposure to public speaking; exposure to

sweating and public speaking


Group Habituation Conditioning Drug Extinction Extinction

Ingestion Phase 1 Phase 2

CSA (4) CSA + US (8) CSA (8) CSA (8)

Single Placebo CSB (4) CSB + US (8) Placebo CSB (8) CS- (8)

CS- (4) CS- (8) CS- (8)

CSA (4) CSA + US (8) CSA (8) CSAB (8)

Compound Placebo CSB (4) CSB + US (8) Placebo CSB (8) CS- (8)

CS- (4) CS- (8) CS- (8)

CSA (4) CSA + US (8) CSA (8) CSA (8)

Single Caffeine CSB (4) CSB + US (8) Caffeine CSB (8) CS- (8)

CS- (4) CS- (8) CS- (8)

CSA (4) CSA + US (8) CSA (8) CSAB (8)

Compound Caffeine CSB (4) CSB + US (8) Caffeine CSB (8) CS- (8)

CS- (4) CS- (8) CS- (8)


Skin Conductance Responses to CSA or CSAB

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Extinction Phase 1 Trial 8 (CSA) Extinction Phase 2 Trial 1 (CSA or CSAB)

Trial

Skin

Con

duct

ance

Res

pons

e

CC CP

SC SP

Figure 29


CSA at Spontaneous Recovery Test

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

CC CP SC SP

Group

Skin

Con

duct

ance

Res

pons

e

**

Figure 33

Group Habituation Conditioning Extinction

Control CS+ (4) CS+ + US (8) CS+ (24)

CS- (4) CS- (8) CS- (24)

Reinforced CS+ (4) CS+ + US (8) CS+ (24)*

CS- (4) CS- (8) CS- (24)

*2:8 Partial Reinforcement Schedule, 6 total CS+ + US pairings

Culver, Stephens & Craske, in submissionCulver, Stephens & Craske, in submission

Partial reinforced trials during extinction are surprising increase salience of CS facilitates learning of CS-noUS on subsequent trials (e.g., exposure to public speaking with occasional ridicule)

CS+ during Extinction

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Trial

Skin

Con

duct

ance

Res

pons

eControl

Reinforced

Figure 7

Culver, Stephens, & Craske, in submissionCulver, Stephens, & Craske, in submission

CS+ during Extinction

-6

-4

-2

0

2

4

6

8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Trial

Expe

ctan

cy R

atin

gControl

Reinforced

Figure 9


CS+ from End of Extinction to Spontaneous Recovery Test

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

End of Extinction Spontaneous Recovery Test

Trial

Skin

Con

duct

ance

Res

pons

eControl

Reinforced

Figure 15



Craske et al., 2008; Craske et al., 2012

VARIABILITYVARIABILITY

• Random and variable practice enhances retrievability of newly learned information (Magill & Hall, 1990)

• Increases storage strength (Bjork & Bjork, 2992)• Stimulus fluctuation theory - more retrieval cues (Bjork &

Bjork, 1992)• Generalization - generates a rule that captures the

invariance among tasks (Schmidt & Bjork, 1992)

• In contrast, traditional exposure based treatments employed blocked and constant practice

Rowe & Craske, 1998, Behaviour Research & Therapy

• Lang & Craske, 2000– Acrophobia

– Blocked = repeat exposure to same height four times, in the same manner, before proceeding to the next height

– Random = move randomly from one height to the next, and approach in multiple ways

VARIABILITYVARIABILITY

Acrophobia: Final Height in BAT

Lang & Craske, 2000, Behaviour Research & TherapyAutonomic arousal and subjective distress did NOT habituate in Varied Group

Contaminant AnxietyPreBAT

PostBAT

2 Week Follow-UpBAT

Random Variable

3 sessions

BlockMassed

3 sessions

Kircanski, Mystkowski, Mortazavi, Baker & Craske, 2012J of Beh Ther & Exp Psych

Exposure Session RV Group BM Group

Session 1

Session 2

Session 3

Same number of exposure tasks (total and with each item), and total minutes of exposure

Look at close (7 min.)…Spread on body (7 min.)





Spread on body (6 min.)…Look at close (8 min.)

SUDS during exposure (third day)Kircanski, Mystkowski, Mortazavi, Baker & Craske, 2012

SUDS for novel BAT itemsKircanski, Mystkowski, Mortazavi, Baker & Craske, 2012

d=.20

HR for novel BAT itemsKircanski, Mystkowski, Mortazavi, Baker & Craske, 2012

d=.37

Contaminant Fear: Emotional Variability Throughout Exposure, R2 = .19

(Kircanski, Mystkowski, Mortazavi, Baker & Craske, 2012)

Above and beyond starting fear, peak fear, ending fear, fear habituation

Public Speaking Fear: Emotional Variability Throughout Exposure, R2=.12(Culver, Stoyanova, & Craske, 2012)

Above and beyond starting fear, peak fear, ending fear, fear habituation

VARIABILITY IN FEARVARIABILITY IN FEAR

• Variability in fear (ups and downs) throughout exposure may enhance long-term outcome because:

– Emotional state as retrieval cue or context (Bjork & Bjork, 1992, 2006; Bouton et al., 2006)

– Repeated opportunities to disconfirm expectancies for negative outcomes (i.e., deepened extinction; Rescorla, 2006)

– Engagement (vs avoidance) throughout exposure and flexible responding to cues (vs rules)


Craske et al., 2008; Craske et al., in press;

Extinction and Affect LabelingExtinction and Affect Labeling

Language in

response to

emotional

stimuli

Increased

Activation of the

RVLPFC

Decreased

Amygdala

Activity

Improved managem

ent of negative

affectActivation of the Medial Prefrontal

Cortex (mPFC)

Extinction: primarily medial PFC believed to inhibit amygdala at recall of extinction (Sotres-Bayon, Cain, & Le Doux, 2006)

Affect Labeling: Disruption Theory (Lieberman, 2007)

Healthy Controls (within group)(Tabibnia, Lieberman & Craske, 2008, Emotion)

+

3.5 sec 2.5 sec 5, 6, or 7 sec

BOMB

ExposureOnly

NegativeLabel(Irrelevant)

Day 1

NegativeLabel(Relevant)

NeutralLabel(Relevant)

FACE

BLOOD

3.5 sec 2.5 sec 5, 6, or 7 sec

3.5 sec 2.5 sec 5, 6, or 7 sec

3.5 sec 2.5 sec 5, 6, or 7 sec


6 sec 5, 6, or 7 sec

ExposureOnly


Day 8


NeutralLabel(Relevant)

NovelPictures






0.25

0.30

0.35

0.40

0.45

0.50

Exposure Only Negative LabelIrrelevant

Negative LabelRelevant

Neutral LabelRelevant

Novel

SCR

(µSi

emen

s)

Day1Day8

p < 0.05

p < 0.05 p < 0.0005 p < 0.01 p = n.s.

Spider Fearful (between group)(Tabibnia, Lieberman & Craske, 2008, Emotion)

+

3.5 sec 2.5 sec 5, 6, or 7 sec

WAR

ExposureOnlyGroup

NegativeLabelGroup

Day 1

NeutralLabelGroup

PET

3.5 sec 2.5 sec 5, 6, or 7 sec

3.5 sec 2.5 sec 5, 6, or 7 sec

--------------------------------------------------------

--------------------------------------------------------

Day 1

Day 1

Spider Fearful (between group)(Tabibnia, Lieberman & Craske, 2008, Emotion)

0.25

0.30

0.35

0.40

0.45

0.50

Exposure Only Negative Label Neutral Label

SCR

(µSi

emen

s)

Day1Day8 ExposedDay8 Novel

p < 0.0005 p < 0.05 p < 0.07

p < 0.01

irrelevant

Role of VLPFC-MPFC: Healthy controls(Tabibnia, Craske, & Lieberman, in submission)

+

BOMB

ExposureOnly


Day 1: fMRI


ControlNeutralPictures

+

BLOOD

3.5 sec 2.0 sec 0.5 sec

3.5 sec 2.0 sec 0.5 sec

3.5 sec 2.0 sec 0.5 sec

3.5 sec 2.0 sec 0.5 sec

Role of VLPFC-MPFC: healthy controls(Tabibnia, Craske, & Lieberman, in submission)


ExposureOnly


Day 8: Psychophysiology


ControlNeutralPictures

NovelNegativePictures





Affect LabelingAffect Labeling• Tabibnia, Lieberman & Craske (2008): affect labeling enhanced fear

attenuation at follow-up (skin conductance response and heart rate) relative to fixation cross

• Tabibnia, Craske & Lieberman (in submission): neural correlates during affect labeling predict skin conductance one week later:

NegRel v. Jitter (text)

-0.20

-0.15

-0.10

-0.05

0.00

0.05

0.10

0.15

0.20

-2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0

RVLPFC activity

SCR

chan

ge (µS

iem

ens)

r = -0.66

NegRel v. Jitter (text)

-0.20

-0.15

-0.10

-0.05

0.00

0.05

0.10

0.15

0.20

-2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0

MPFC activity

SCR

chan

ge (µS

iem

ens)

r = -0.69

Affect Labeling in Exposure SessionsKircanski, Lieberman & Craske (in press) Psych Science

Labeling Reappraisal

Distraction

Exposure-Alone

E.g., “Sitting in front of the ugly spider makes me very nervous.”

E.g., “Sitting in front of the little spider is not dangerous for me.”

E.g., “There is a table in front of the couch in my den.”

-1

-0.5

0

0.5

1SC

R Ch

ange

Immediate Post-Test to One-Week Post-Test

Affect LabelingReappraisalDistractionExposure-Alone

0

0.5

1

1.5

2

Num

ber o

f Add

ition

al S

teps

Co

mpl

eted

Immediate Post-Test to One-Week Post-Test

Affect Labeling

Reappraisal

Distraction

Exposure-AloneLabeling superior to reappraisal

Labeling akin to acceptance

Brief Acceptance and Commitment Therapy and Exposure for Panic Disorder: A pilot study.Alicia E. Meuret1, Michael P. Twohig2, David Rosenfield1, Steve C. Hayes3, & Michelle G. Craske 4

CBT vs ACT:Arch, J. J., Eifert, G. H., Davies, C., Plumb, J. C., Rose, R.

D., & Craske, M. G., in press, JCCP

Inclusion Criteria:• met DSM-IV-TR diagnostic criteria for one or more anxiety disorders with a

Clinician Severity Rating (CSR) ≥ 4 on the Anxiety Disorders Interview Schedule-IV

• Ages 18-60• Medication-free or stabilized on medication• Not undergoing other psychotherapy

Exclusion Criteria:• history of psychiatric hospitalization in the past 5 years• serious medical conditions/pregnancy• active suicidal ideation and/or severe depression• history of a psychotic disorder, bipolar disorder, mental retardation, or organic

brain damage• substance abuse or dependence within the last 6 months

Treatments

• 12 sessions tailored to the principal anxiety disorder

CBT ACTPsychoeducation & Rationale

= controlPsychoeducation & Rationale

= relinquish controlBreathing retraining Mindfulness & acceptance

Cognitive restructuring Mindfulness & acceptance

Interoceptive exposure Willingness, mindfulness & acceptance of internal cues

Naturalistic and in vivo exposure

Willingness to accept anxiety while moving in direction that is consistent with life values

Shows reliable CSR change1 and Does not meet clinical diagnostic criteria (CSR ≤ 3) Assessment

CBT ACT 2 p Post-treatment 51.0% (25/49) 44.7% (17/38) .34 .56

6-month 59.5% (22/37) 44.4% (12/27) 1.41 .24

12-month 50.0% (16/32) 54.5% (12/22) .11 .74

1 Reliable change required the following minimum improvement values from pre-treatment (see Supplementary Materials for computational details): principal disorder clinical severity rating (CSR) = 2.75

Arch, J. J., Eifert, G. H., Davies, C., Plumb, J. C., Rose, R. D., & Craske, M. G., in press, JCCP

Moderators:Moderators:Mood disorder comorbidityMood disorder comorbidity

p < .01

p = .01

NS

p = .05

Significant Mood comorbidity x Group interaction

Moderators: Anxiety sensitivityModerators: Anxiety sensitivity

NS

NS p < .05

p < .01

NS

Significant Group x ASI2 interaction

Moderators: Experiential AvoidanceModerators: Experiential Avoidance

Significant AAQ2 x Group interaction at 12-mo

NS

p < .01

NS NSp < .05

High experiential avoidance Low experiential avoidance

DESIGNBaselineScreenADIS

Lab TasksQuestionnaires

fMRI

12 Weeks

CBT ACT WL

PostADIS


fMRI

Follow-upADIS


Ses

sion

By

Ses

sion

Med

iato

r M

easu

res

Craske et al., in prep

PARTICIPANTS

INCLUSION CRITERIAPrincipal diagnosis of Social Anxiety Disorder

18-45 years of ageRight handed

English speaking

EXCLUSION CRITERIASubstance abuse/dependence last 6 months

Serious medical conditionsSevere depression or active suicidality

History of bipolar, psychosis, MR, brain damageHistory of psychiatric hospitalizations in last 5 years

OUTCOME MEASURES

ADIS-IV CSR Social AnxietyADIS-IV CSR Most Severe Comorbid DisorderAdditional Treatment

Symptoms - SIAS (Social Interaction Anxiety Scale) - SPS (Social Phobia Scale) - LSAS-SR (Liebowitz Social Anxiety Scale-Self-Report) - SSPI (Self Statements During Public Speaking)Acceptance - FFMQ (Five Faces Mindfulness Questionnaire) - MMAS (Mindful Attention Awareness) - AAQ-16 ( Acceptance and Action Questionnaire)Quality of Life InventoryACQ (Anxiety Control Questionnaire)

DIAGNOSTIC

QUESTIONNAIRES

Laboratory Assessment

• Spatial cueing

• IAPS

• Hyperventilation (first and second)

• Public speaking

fMRI tasks

• Affect labeling (faces)

• Video clips of facial expressions and matching verbal statements (pos, neg, neutral):– (1) imagine that these people are saying this to you – (2) notice (accept) emotional response – (3) decrease emotional response

• Observe self giving speech

• Prepare to give speech after fMRI (pre only)

• Cyberball task (post only)

ConclusionConclusion• The long term success of exposure

therapy depends on strength and retrievability of inhibitory associations and underlying neural regulation

• Fear reduction within exposure therapy has little to do with long term outcomes

ConclusionConclusion• Exposure outcomes enhanced by strategies

such as– increased number of phobic stimuli (increases fear

arousal)– occasional negative outcomes (sustained fear

arousal)– variability of stimuli and emotional response

(sustained fear arousal)– affect labeling of emotions and stimuli (akin to

acceptance based approaches)

ConclusionConclusion• Comparison between treatment packages

(CBT and ACT) useful but does not expand out understanding of exposure mechanisms

• Need for more mechanistic research

Documents

Exposure Therapy for Anxiety Disorders: From Fear Reduction to Fear Enhancement