Can we Treat Neuroticism:
December , 2013: The Evolution of Psychotherapy
David H. Barlow, PhD, ABPP
Professor of Psychology and Psychiatry
Founder and Director Emeritus, Center for Anxiety & Related Disorders Boston
University
DSM IV
Anxiety and Mood Disorders
Substantial phenotypic overlap
High comorbidity
Necessity of NOS diagnoses (mostly GAD)
Subthreshold presentations (mostly OCD, MAD
& SAD)
Higher order dimensions account for covariance
among DSM IV constructs
DSM IV
“Zenith of splitting” (reliably identified but narrow
slices of psychopathology)
DSM-5
“Return to lumping” (based on the deepening
knowledge of underlying dimensions of
psychopathology and supporting brain circuitry)
Metastructure of DSM 5
ANXIETY DISORDERS
Separation Anxiety Disorder
Selective Mutism
Panic Disorder
Agoraphobia
Specific Phobia
Social Anxiety Disorder (Social Phobia)
Generalized Anxiety Disorder
Substance-Induced Anxiety Disorder
Anxiety Disorder Attributable to Another Medical
Condition
Anxiety Disorder Not Elsewhere Classified
Panic Attack
Metastructure of DSM 5
OBSESSIVE-COMPULSIVE AND RELATED DISORDERS
Obsessive-Compulsive Disorder
Body Dysmorphic Disorder
Hoarding Disorder
Trichotillomania (Hair-Pulling) Disorder
Excoriation (Skin-Picking) Disorder
Substance-Induced ObsessiveCompulsive, or Related Disorders
Obsessive-Compulsive, or Related Disorder
Attributable to Another Medical Condition
Obsessive-Compulsive, or Related Disorder
Not Elsewhere Classified
Metastructure of DSM 5
TRAUMA- AND STRESSOR-RELATED DISORDERS
Reactive Attachment Disorder
Disinhibited Social Engagement Disorder
Acute Stress Disorder
Post-traumatic Stress Disorder
Adjustment Disorders
Trauma- or Stressor- Related Disorder Not
Elsewhere Classified
Higher Order Dimensions:
(Temperaments)
• Neuroticism: (Introversion) -- Eysenck
• Behavioral Inhibition System: Behavioral Activation System (BIS-BAS)
-- Gray
• Behavioral Inhibition -- Kagan
• Negative Affect: Positive affect (NA-PA) --Tellegen, Clark, Watson
• Trait anxiety –(Barlow, 1988; Cattell, 1963)
Higher Order Dimensions:
(Temperaments)
Trait Anxiety /Neuroticism / Behavioral Inhibition (A/N/BI)
Behavioral activation / Positive Affect
(BA/P)
-.36*
Positive
Affect
-.28*
-.29*
-.67*
.74*
.18*
.33*
Depression
.65*
.58*
.45*
.50*
Negative
Affect
Generalized
Anxiety
Disorder
.43*
-.22*
.67*
-.11*
Autonomic
Arousal
Brown, T. A., Chorpita, B. F., & Barlow, D. H.,1998.
.76*
.81*
Panic
Disorder/
Agoraphobia
ObsessiveCompulsive
Disorder
.02
.31*
-.02
Social
Phobia
Temporal Course of Temperamental Dimensions
N = 606
75% treated at CARD
o followed for 2 years whether treated or not.
Principal DX: Unipolar Mood, GAD, Social Anxiety
Broad patterns of comorbidity
Brown, T. A., 2007
Conceptualization
All constructs dimensionalized as:
N/BI
BA/P
DEP
SOC
GAD
Generalized Anxiety Disorder
Intake 12MFU 24MFU Time
Model-Implied Trajectories of DSM-IV Disorder Constructs as a
Function of Neuroticism/Behavioral Inhibition. Note. N/BI =
Neuroticism/Behavioral Inhibition. (N=606).
Brown, T. A., 2007
Some results and future questions
BA/P most stable
Largest effect size for N/BI
Disorder effect sizes intermediate
More severe N/BI is associated with smaller tx effects
Do changes in N/BI mediate overall change?
Is the Axis I and II distinction a false dichotomy?
Origins of Trait Anxiety/Neuroticism
Triple Vulnerability Theory
Barlow, D. H., 2000; 2002; Suárez, L., Bennett, S., Goldstein, C., & Barlow, D.H. (2009).
Independent Vulnerabilities
Biological Vulnerability
(heritable contribution to
negative affect)
• “Glass is half empty”
• Irritable
• Driven
Generalized
Psychological
Vulnerability
(sense that events are
uncontrollable/
unpredictable)
Specific Psychological
Vulnerability
(e.g., physical sensations are
potentially dangerous)
• Hypochondriac?
• Nonclinical panic?
• Tendency towards
lack of self-confidence
• Low self-esteem
• Inability to cope
Generalized
Biological
Vulnerability
Polygenic Model of Vulnerability
“Susceptibility genes… represent particular allelic
variations of common genes.”
(Rutter, Moffitt, & Caspi, 2006)
“Gene discovery… is, on its own, unlikely to allow us
to carve nature at its joints.”
(Kendler, 2006)
Generalized
Psychological
Vulnerability
Generalized Psychological Vulnerability
Early disruptive experiences produce a (permanent) sense
(schema) of unpredictability, uncontrollability, and an inability to
cope with potentially threatening events. “Experimental Neurosis” –
Pavlov, Masserman, Liddell (Mineka & Kihlstrom, 1978).
These experiences are associated with stable change in brain
structure and function, including gene expression. (Sapolsky 2007;
Gillespie & Nemeroff, 2007; Spinelli, Chefer, Suomi, Higley, Barr, & Stein, 2009.)
Disruptive early experiences are not restricted to early trauma –
other experiences such as certain parenting styles induce
diminished sense of personal control. (Chorpita & Barlow, 1998.)
Consequence is not any one specific disorder.
STRESS
loss of
control
lack of
prediction
no outlets
for
frustration
chronic
threats
social
subordinance
increased
corticotrophin
-releasing
factor
hypercortisolism
reduced
inhibitory
feedback
Glucocorticoid
Cascade
hippocampal
degeneration
From Sapolsky, 1992 ; 2007; Sapolsky et al., 1997.
damage and
exacerbation of
insults
Effect Sizes (d) for Hypothalamic-PituitaryAdrenocortical Outcomes According to Stress
Cortisol
Daily Output
Daily Output
Nature of threat
D
SE
Physical threat
+0.46
0.07
Social Threat
-0.04
0.11
Traumatic Stressor
+0.51
0.07
Uncontrollable
+0.43
0.06
Potentially controllable
-0.04
0.11
Loss
-0.06
0.07
Shame
+0.07
0.09
Miller, G.E., Chen, E., & Zhou, E. S., 2007.
Diatheses
Synergistic Vulnerabilities
BIOLOGICAL VULNERABILITY
GENERALIZED PSYCHOLOGICAL VULNERABILITY
STRESS
GENERALIZED ANXIETY
Depression
FALSE ALARMS
(PANIC)
Independent Vulnerabilities
Biological Vulnerability
(heritable contribution to
negative affect)
• “Glass is half empty”
• Irritable
• Driven
Generalized
Psychological
Vulnerability
(sense that events are
uncontrollable/
unpredictable)
Specific Psychological
Vulnerability
(e.g., physical sensations are
potentially dangerous)
• Hypochondriac?
• Nonclinical panic?
• Tendency towards
lack of self-confidence
• Low self-esteem
• Inability to cope
Specific Psychological Vulnerabilities
OCD
SOCIAL ANXIETY
“Thinking an evil thought is as bad “Always look your best” (Social
as doing it” (Thought-action fusion evaluation is dangerous and
rigid codes of conduct-excessive
threatening)
responsibility-religiosity)
SPECIFIC PHOBIA
PANIC DISORDER
“If you’re sick-go right to bedavoid strenuous activities”
(Physical symptoms and
sensations are potentially
dangerous)
“Watch out for dogs (snakes,
heights, thunderstorms)”
OTHER DISORDERS
Eating Disorders
Somatoform Disorders
Mediating Emotional
Experiences in Genesis of
Specific Emotional Disorders
Means and Standard Deviations for Stimulus-Naïve Participants
on Measures of Emotional Appraisal and Regulation during the
First Emotion Induction
Measure
Clinical Participants
MES-A
MES-C
SUPP
MRS-R
MRS-M
SELF
WILL
23.37 (5.22)
22.67 (5.43)
3.50 (2.17)
12.28 (5.50)
15.52 (5.03)
5.07 (2.64)
5.72 (2.46)
Nonclinical Participants
26.26 (2.74)*
24.04 (4.72)
2.11 (2.03)*
11.96 (5.57)
15.67 (4.30)
6.33 (2.18)**
6.36 (2.30)
Note. Values are mean scores with standard deviations in parentheses.
MES-A = Meta Evaluation Scale-Acceptability; MES-C = Meta Evaluation Scale-Clarity;
SUPP = Suppression Rating; MRS-R = Meta Regulation Scale-Repair;
MRS-M = Meta Regulation Scale-Maintenance; SELF = Self Efficacy Rating;
WILL = Willingness Rating.
* p < .02
** p < .05
Campell-Sills, Barlow, Brown, & Hofmann, 2006.
Panic Attack
Interoceptive and Other Forms of Conditioning
Interoceptive conditioning happens
– Intestinal distension  10% CO2 to trachea
 Hypercapnic respiratory changes as CR
– Pentobarbital  morphine
USs can signal other USs
Small things can signal bigger versions of the same thing
– Small alcohol dose signals bigger alcohol dose
– Small morphine dose signals bigger morphine dose
– Early onset cues signal later aspects of the same event
Barlow, 1988; Bouton, Mineka, & Barlow, 2001.
Model of the Persistence of Emotional Distress Featuring Perceived Acceptability of
Emotions and Emotional Suppression
Emotion
perceived as
intolerable/
unacceptable
Efforts to
suppress
Suppression
Fails
No suppression
Mood recovers
naturally
Negative
affect
Emotion
perceived as
tolerable/
acceptable
Campell-Sills & Barlow, 2007.
Examples of Avoidance Strategies
Behavioral and Interoceptive Avoidance
Avoidance Strategy
Situational avoidance/escape
Avoidance/escape from phobic situations (e.g., crowds,
parties, elevators, public speaking, theaters, animals)
Subtle behavioral avoidance
Avoidance of eye contact (e.g., wearing sunglasses)
Avoidance of sensation-producing activities (e.g.,
physical exertion, caffeine, hot rooms)
Avoidance of “contaminated” objects (e.g., sinks,
toilets, doorknobs, money)
Perfectionistic behavior at work or home
Procrastination (avoidance of emotionally salient tasks)
Repetitive or ritualistic behaviors
Compulsive acts (e.g., excessive checking, cleaning)
Disorder Often Associated
PD/A, SOC, SPEC
SOC
PD/A
OCD
GAD, SOC, OCD
GAD, DEP
OCD
Examples of Avoidance Strategies
Cognitive and Emotional Avoidance
Avoidance Strategy___________________________Disorder Often Associated
Cognitive avoidance/escape
Dissociation (depersonalization, derealization)
PDA, PTSD
Distraction (e.g., reading a book, watching television
GAD, DEP, PD/A
Avoidance of thoughts or memories about trauma
PTSD
Effort to prevent thoughts from coming into mind
OCD, PTSD
Worry
GAD
Rumination
DEP
Thought Suppresion
All Disorders
Safety Signals
Carrying a cell phone
PD/A, GAD
Holding onto “good luck” charms
OCD
Carrying water or empty medication bottles
PD/A
Having reading materials always on hand
SOC, GAD
Carrying self-protective materials (e.g. mace, siren)
PTSD
Brown & Barlow, 2009.
Case Example
53 year-old white male teacher – “PM”
Traffic accident 6 months earlier
– Intrusive recollections and re-experiencing (injured wife’s face, sound of impact
“crisp like a CD player”)
– Amnesia for events surrounding accident
– Startle response
US Air Force in Vietnam
– Recollections and re-experiencing
– Avoid war cues
– Emotional numbing, nightmares, difficulty sleeping, detachment from others (no
longer present)
Diagnosi
s
health
PTSD 6
Anx NOS 5 (GAD) worries about performance,
Brown & Barlow, 2009.
Proposed DSM 5 (or 6) Dimensional Diagnosis of a
Case with PTSD
Temperament
Brown & Barlow, 2009.
Mood
Focus of Anxiety
Avoidance
Multi-dimensional emotional
disorders inventory (MEDI)
Present Status: A Crossroad
Effective treatment, but plenty of room for improvement
Too many distinct protocols–manuals
Protocols still relatively complex-restricting disseminations
Development of a
Transdiagnostic
Unified
Treatment
Unified Protocol: A Modular Approach
Module 1: Motivation Enhancement for Treatment Engagement
(1 session)
Module 2: Psychoeducation and Treatment Rationale (1-2 sessions)
Module 3: Emotional Awareness Training (1-2 sessions)
Module 4: Cognitive Appraisal and Reappraisal (1-2 sessions)
Module 5: Emotion Driven Behaviors (EDBs) and
Emotional Avoidance (1-2 sessions)
Module 6: Interoceptive Awareness and Tolerance (1-2 sessions)
Module 7: Situational Exposures (3-6 sessions)
Module 8: Relapse Prevention (1 session)
Barlow et al., 2011
Putative Mechanism of Action
Reduction of experiential emotional avoidance and
associated extinction of anxiety and distress
triggered by intense emotional experiences
Proportion Achieving Responder Status and High EndState Functioning:
ADIS-IV Principal Diagnosis CSR
Study Condition
Post- Treatment / WL
6-Month Follow-Up
N
%Treatment
Responders
% HES
Fx
N
%Treatment
Responders
% HES
Fx
UP Treatment
22
55%
55%
20
75%
75%
WL Control
10
0%
0%
Note: HES Fx= High End-State Functioning.
Effects on NA – UP Version 2.0
Significant effect of time on NA
(F1,13=10.55, p<.001)
Clinical significance of change in NA:
– Pre-treatment – 27% patients achieved
scores within normal range
– Post-treatment – increased to 67% (as
compared to 56% in study 1)
– 6-month follow-up – increased further to 82%
Ellard et al., 2012
Post-Training Amygdala
1
Training
No Training
Activation
0.5
0
-0.5
-1
-1.5
Accept
Suppress
Worry
Post-Training vmPFC
0.2
0
-0.2
Activation
-0.4
-0.6
-0.8
-1
-1.2
-1.4
Training
No Training
-1.6
Accept
Suppress
Worry
Post-Training sgACC
2
1.5
1
Activation
0.5
0
-0.5
-1
-1.5
Training
No Training
-2
Accept
Suppress
Worry
Mechanisms of Antidepressant Drug Treatment
Harmer, Goodwin, & Cowen, 2009
Take Home Messages
• “Splitting” no longer supported empirically or clinically
• Higher-order temperaments better account for:
• Description of emotional disorders
• Origins of Emotional Disorders
• Developing treatments distill common principles to treat
transdiagnostic temperamental features
Thank You
David H. Barlow, PhD, ABPP
Center for Anxiety and Related Disorders, Boston University
www.bu.edu/card
617-353-9610
References
Barlow, D. H. (1988). Anxiety and its disorders: The nature and treatment of anxiety and panic. New York, NY US: Guilford
Press.
Barlow, D. H. (2000). Unraveling the mysteries of anxiety and its disorders from the perspective of emotion theory.
American Psychologist, 55(11), 1247-1263.
Barlow, D. H. (2002). Anxiety and its disorders: The nature and treatment of anxiety and panic (2nd ed.). New York: The
Guilford Press.
Barlow, D.H., Ellard, K.K., Fairholme, C.P., Farchione, T.J., Boisseau, C.L. Allen, L.B. & Ehrenreich-May, J. (2011). The
unified protocol for transdiagnostic treatment of emotional disorders: Client workbook. New York, NY: Oxford University
Press.
Barlow, D.H., Farchione, T.J., Fairholme, C.P., Ellard, K.K., Boisseau, C.L. Allen, L.B. & Ehrenreich-May, J. (2011). The
unified protocol for transdiagnostic treatment of emotional disorders: Therapist guide. New York, NY: Oxford University
Press.
Bouton, M. E., Mineka, S., & Barlow, D. H. (2001). A modern learning theory perspective on the etiology of panic disorder.
Psychological Review, 108(1), 4-32.
Brown, T. A. (2007). Temporal course and structural relationships among dimensions of temperament and DSM-IV anxiety
and mood disorder constructs. Journal of Abnormal Psychology, 116(2), 313-328.
Brown, T. A., Campbell, L. A., Lehman, C. L., Grisham, J. R., & Mancill, R. B. (2001). Current and lifetime comorbidity of
the DSM-IV anxiety and mood disorders in a large clinical sample. Journal of Abnormal Psychology, 110(4), 585-599.
Brown, T. A., Chorpita, B. F., & Barlow, D. H. (1998). Structural relationships among dimensions of the DSM-IV anxiety
and mood disorders and dimensions of negative affect, positive affect, and autonomic arousal. Journal of Abnormal
Psychology, 107(2), 179-192.
Brown, T. A., Di Nardo, P. A., Lehman, C. L., & Campbell, L. A. (2001). Reliability of DSM-IV anxiety and mood disorders:
implications for the classification of emotional disorders. Journal of Abnormal Psychology, 110(1), 49-58.
References (continued)
Campbell-Sills, L., & Barlow, D. H. (2007). Incorporating Emotion Regulation into Conceptualizations and Treatments of
Anxiety and Mood Disorders. In J. J. Gross (Ed.), Handbook of emotion regulation. (pp. 542-559). New York, NY US:
Guilford Press.
Campbell-Sills, L., Barlow, D. H., Brown, T. A., & Hofmann, S. G. (2006a). Acceptability and suppression of negative
emotion in anxiety and mood disorders. Emotion, 6(4), 587-595.
Campbell-Sills, L., Barlow, D. H., Brown, T. A., & Hofmann, S. G. (2006b). Effects of suppression and acceptance on
emotional responses of individuals with anxiety and mood disorders. Behaviour Research and Therapy, 44(9), 1251-1263.
Cattell, R. B. (1963). The nature and measurement of anxiety. Scientific American, 208, 96-104.
Chorpita, B.F. & Barlow, D.H. (1998). Perceived control as a mediator of family environment in etiological models of
childhood anxiety. Behavior Therapy, 29, 457-476.
Ellard, K. K., Fairholme, C. P., Boisseau, C. L., Farchione, T. J., & Barlow, D. H. (2010). Unified Protocol for the
transdiagnostic treatment of emotional disorders: Protocol development and initial outcome data. Cognitive and Behavioral
Practice.
Fairholme, C. P., Boisseau, C. L., Ellard, K. K., Ehrenreich, J. T., & Barlow, D. H. (2010). Emotions, emotion regulation, and
psychological treatment: A unified perspective. In A. M. Kring & D. M. Sloan (Eds.), Emotion regulation and
psychopathology: A transdiagnostic approach to etiology and treatment. (pp. 283-309). New York, NY US: Guilford Press.
Farchione, T.J., Fairholme, C.P., Ellard, K.K., Boisseau, C.L., Thompson-Hollands, J., Carl, J.R., Gallagher, M. & Barlow, D.
H. (In press).The unified protocol for the transdiagnostic treatment of emotional disorders: A randomized controlled trial.
Behavior Therapy.
Gillespie, C. F., & Nemeroff, C. B. (2007). Corticotropin-releasing factor and the psychobiology of early-life stress. Current
Directions in Psychological Science, 16(2), 85-89.
Harmer, C. J., Goodwin, G. M., & Cowen, P. J. (2009). Why do antidepressants take so long to work? A cognitiveneuropsychological model of antidpressant drug action. British Journal of Psychiatry, 195, 102-108.
Jacobson, N. S., & Truax, P. (1991). Clinical significance: A statistical approach to defining meaningful change in
psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12–19.
References (continued)
Kendler, K. S. (2006). Dr. Kendler replies. The American Journal of Psychiatry, 163(12), 2198-2198.
Miller, G. E., Chen, E., & Zhou, E. S. (2007). If it goes up, must it come down? Chronic stress and the hypothalamic-pituitaryadrenocortical axis in humans. Psychological Bulletin, 133(1), 25-45
Mineka, S., & Kihlstrom, J. F. (1978a). Unpredictable and uncontrollable events: a new perspective on experimental neurosis.
Journal of Abnormal Psychology, 87(2), 256-271.
Mineka, S., & Kihlstrom, J. F. (1978b). Unpredictable and uncontrollable events: A new perspective on experimental neurosis.
Journal of Abnormal Psychology, 87(2), 256-271.
Rutter, M., Moffitt, T. E., & Caspi, A. (2006). Gene-environment interplay and psychopathology: Multiple varieties but real
effects. Journal of Child Psychology and Psychiatry, 47(3), 226-261.
Sapolsky, R. M. (1992). Stress, the aging brain, and the mechanisms of neuron death. Cambridge, MA US: The MIT Press.
Sapolsky, R. M. (2007). Stress, Stress-Related Disease, and Emotional Regulation. In J. J. Gross (Ed.), Handbook of emotion
regulation. (pp. 606-615). New York, NY US: Guilford Press.
Sapolsky, R. M., Alberts, S. C., & Altmann, J. (1997). Hypercortisolism associated with social subordinance or social isolation
among wild baboons. Archives of General Psychiatry, 54(12), 1137-1143.
Spinelli, S., Chefer, S., Suomi, S. J., Higley, J. D., Barr, C. S., & Stein, E. (2009). Early-life stress induces long-term
morphologic changes in primate brain. Archives of General Psychiatry, 66(6), 658-665.
Suárez, L. M., Bennett, S. M., Goldstein, C. R., & Barlow, D. H. (2009). Understanding anxiety disorders from a 'triple
vulnerability' framework. In M. M. Antony & M. B. Stein (Eds.), Oxford handbook of anxiety and related disorders. (pp. 153172). New York, NY US: Oxford University Press.
Wilamowska, Z.A., Thompson-Hollands, J., Fairholme, C.P., Ellard, K.K., Farchione, T.J., & Barlow,
D.H. (2010). Conceptual background, development, and preliminary data from the unified protocol for transdiagnostic
treatment of emotional disorders. Depression and Anxiety, 27, 882-890. doi: 10.1002/da.20735