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

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Exposure Therapy for Anxiety Disorders From Fear
Reduction to Fear Enhancement

• Michelle G. Craske, Ph.D.
• July, 2012
• Professor of Psychology
• Professor of Psychiatry and Biobehavioral
  Sciences
• Director, UCLA Anxiety Disorders Research Center
• UCLA

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Exposure Therapy

• Repeated, systematic exposure to feared stimuli
• In vivo situations, objects, places, people
• Interoceptive sensations
• Imaginal images and memories

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Exposure 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

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Exposure-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)

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QUESTIONS

• 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

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RECIPROCAL 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)

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EMOTIONAL PROCESSING THEORY (Foa Kozak, 1986
Foa McNally, 1996)Fear Structure
Within session Habituation of fear
Stimulus
Response
Threat Meaning
Neutral Meaning
Between session Habituation of fear
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FEAR REDUCTION

• Stay in the situation until fear subsides
• Is fear reduction predictive of outcome?

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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)

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

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Spider Fears Pre BAT
Exposure Trials 3 min, 1 min ITI Fear lt 10 (4.3)
Overlearning 200 more (10.7)
Control No more
Post BAT
3-week Follow-Up BAT
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Farchione Craske, 2002
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FEAR 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)

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FEAR EXPRESSION VS FEAR LEARNING

• 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)

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FEAR EXPRESSION VS FEAR LEARNING

• 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)

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Mechanisms 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)

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PRE-EXPOSURE-------EXPOSURE-----------------------
---------------------POST-EXPOSURE
Time
Context
New Adverse Events
Retrieval Cues
In tact
Excitatory Threat Expectancy
?
Habituation not a central mechanism
Inhibitory Nonthreat Expectancy
No Fear
Fear
Mismatch with expectancy for adverse events
Neural inhibitory regulation vmPFC over amygdala
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INHIBITORY 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?

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ANXIETY 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)

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Craske, Waters, Bergman et al., 2008Behavior
Research Therapy
Control High Risk Anxious
Child No diagnoses N 15 No diagnoses N 13 Anxiety diagnoses N 24
Mother/Father No diagnoses Anxiety diagnoses Mixed group
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Method

• Acquisition phase
• 16 trials
• 8 CS (geometric shape paired with 107db tone)
• 8 CS- (alternate shape presented alone)

Tone
CS
CS-
0 s
7 s 8 s
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16 trials 8 CS (UCS), 8 CS-
8 trials 4 CS , 4 CS-
8 trials 4 CS , 4 CS-
acquisition
extinction
1 week
spontaneous recovery
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Craske, Waters, Bergman et al., 2008Behavior
Research Therapy
Conditioning F(1, 110) 7.88, p lt .001, ß
-.15 Extinction F(1, 55) 6.19, p .003, ß
-.10 Extinction retest F(1, 50) 9.54, p
.003, ß -.09
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ANXIETY 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)

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Craske et al., 2009, 2012
8 context trials
8 baseline trials
8 context trials
8 baseline trials
Safe Danger Phases
Stimulation
5 35
15 45
5 35
15 45
5 35
15 45
5 35
15 45
















0 55 0 55 0
55 0 55 0 55 0
55 0 55 0 55
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• SAFE NO CONTRACTION WILL BE GIVEN

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• DANGER CONTRACTION MAY BE GIVEN
• Count down

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Craske, Waters et al. (2009). Biological
Psychiatry
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Prediction of Onset of Anxiety Disorders
Safe/Danger SR Intercepts Craske et al., 2012 J
of Abnormal Psychology
Before Contraction
After Contraction
plt.05
Effects for ADs above and beyond covarying N,
UDD, danger
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INHIBITORY 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

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Craske et al., 2008 Craske et al., 2012
Not erasure of fear memory-reconsolidation
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Culver, 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

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Culver, Vervliet, Craske, in submission
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)  
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Culver, Vervliet, Craske, in submission
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Culver, Vervliet, Craske, in submission
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Culver, Stephens Craske, in submission
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)
28 Partial Reinforcement Schedule, 6 total CS US pairings 28 Partial Reinforcement Schedule, 6 total CS US pairings 28 Partial Reinforcement Schedule, 6 total CS US pairings 28 Partial Reinforcement Schedule, 6 total CS US pairings
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)
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Culver, Stephens, Craske, in submission
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Culver, Stephens Craske, in submission
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Culver, Stephens Craske, in submission
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Craske et al., 2008 Craske et al., 2012
Not erasure of fear memory-reconsolidation
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VARIABILITY

• 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

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Rowe Craske, 1998, Behaviour Research Therapy
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VARIABILITY

• 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

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Acrophobia Final Height in BAT
Autonomic arousal and subjective distress did NOT
habituate in Varied Group
Lang Craske, 2000, Behaviour Research Therapy
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Kircanski, Mystkowski, Mortazavi, Baker Craske,
2012 J of Beh Ther Exp Psych
Contaminant Anxiety Pre BAT
Random Variable 3 sessions
Block Massed 3 sessions
Post BAT
2 Week Follow-Up BAT
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Exposure Session RV Group BM Group
Session 1
Session 2
Session 3
Look at close (7 min.) Spread on body (7 min.)
Look at close (2 min.) Spread on body (12 min.)
Look at close (7 min.) Spread on body (7 min.)
Spread on body (6 min.) Look at close (8 min.)
Look at close (7 min.) Spread on body (7 min.)
Look at close (12 min.) Spread on body (2 min.)
Same number of exposure tasks (total and with
each item), and total minutes of exposure
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SUDS during exposure (third day)Kircanski,
Mystkowski, Mortazavi, Baker Craske, 2012
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SUDS for novel BAT itemsKircanski, Mystkowski,
Mortazavi, Baker Craske, 2012
d.20
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HR for novel BAT itemsKircanski, Mystkowski,
Mortazavi, Baker Craske, 2012
d.37
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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
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Public Speaking Fear Emotional Variability
Throughout Exposure, R2.12(Culver, Stoyanova,
Craske, 2012)
Above and beyond starting fear, peak fear, ending
fear, fear habituation
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VARIABILITY 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)

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Craske et al., 2008 Craske et al., in press
Not erasure of fear memory-reconsolidation
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Extinction and Affect Labeling
Extinction primarily medial PFC believed to
inhibit amygdala at recall of extinction
(Sotres-Bayon, Cain, Le Doux, 2006)
Affect Labeling Disruption Theory (Lieberman,
2007)
Increased Activation of the RVLPFC
Improved management of negative affect
Decreased Amygdala Activity
Language in response to emotional stimuli
Activation of the Medial Prefrontal Cortex (mPFC)
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Healthy Controls (within group)(Tabibnia,
Lieberman Craske, 2008, Emotion)
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Healthy Controls (within group)(Tabibnia,
Lieberman Craske, 2008, Emotion)
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Healthy Controls (within group)(Tabibnia,
Lieberman Craske, 2008, Emotion)
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Spider Fearful (between group)(Tabibnia,
Lieberman Craske, 2008, Emotion)
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Spider Fearful (between group)(Tabibnia,
Lieberman Craske, 2008, Emotion)
irrelevant
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Role of VLPFC-MPFC Healthy controls(Tabibnia,
Craske, Lieberman, in submission)
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Role of VLPFC-MPFC healthy controls(Tabibnia,
Craske, Lieberman, in submission)
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Affect 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

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

Reappraisal

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.
Distraction

Exposure-Alone

E.g., There is a table in front of the
couch in my den.
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Labeling superior to reappraisal Labeling akin
to acceptance
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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
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CBT vs ACTArch, 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

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Treatments

• 12 sessions tailored to the principal anxiety
  disorder

CBT ACT
Psychoeducation Rationale control Psychoeducation Rationale relinquish control
Breathing 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
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Arch, J. J., Eifert, G. H., Davies, C., Plumb, J.
C., Rose, R. D., Craske, M. G., in press, JCCP
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
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ModeratorsMood disorder comorbidity
Significant Mood comorbidity x Group interaction
p .01
p lt .01
NS
p .05
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Moderators Anxiety sensitivity
Significant Group x ASI2 interaction
NS
NS
NS
p lt .05
p lt .01
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Moderators Experiential Avoidance
Significant AAQ2 x Group interaction at 12-mo
NS
NS
NS
p lt .05
p lt .01
High experiential avoidance
Low experiential avoidance
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DESIGN
Craske et al., in prep
Baseline Screen ADIS Lab Tasks Questionnaires fMRI
12 Weeks
CBT
ACT
WL
Session By Session Mediator Measures
Post ADIS Lab Tasks Questionnaires fMRI
Follow-up ADIS Lab Tasks Questionnaires
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PARTICIPANTS
INCLUSION CRITERIA Principal diagnosis of Social
Anxiety Disorder 18-45 years of age Right
handed English speaking
EXCLUSION CRITERIA Substance abuse/dependence
last 6 months Serious medical conditions Severe
depression or active suicidality History of
bipolar, psychosis, MR, brain damage History of
psychiatric hospitalizations in last 5 years
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OUTCOME MEASURES
ADIS-IV CSR Social Anxiety ADIS-IV CSR
Most Severe Comorbid Disorder Additional
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
Inventory ACQ (Anxiety Control Questionnaire)
DIAGNOSTIC
QUESTIONNAIRES
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Laboratory Assessment

• Spatial cueing
• IAPS
• Hyperventilation (first and second)
• Public speaking

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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)

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Conclusion

• 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

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Conclusion

• 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)

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Conclusion

• Comparison between treatment packages (CBT and
  ACT) useful but does not expand out understanding
  of exposure mechanisms
• Need for more mechanistic research