1. Effective Rehabilitation of Psychological Injury After MVAs
Richard Bryant
University of New South Wales

2. Outline Injury & Its Effects Current Models The Evidence
How do we do Best Rehabiliation?

3. Effects of Injury
Injury contributes to 12% of world’s burden of disease
WHO: 1 in 5 life-years lost by 2020
1 in 11 people in US treated in ED each year
Psychological factors predict disability beyond effects of physical injury

4. Posttraumatic Stress Disorder (PTSD)
Most common psychiatric disorder after trauma
Includes (DSM-5):
(a) Reexperiencing the trauma (memories)
(b) Avoidance
(c) Alterations in Mood & Cognition
(d) Arousal

5. Treating PTSD Treatment of choice = trauma-focused psychotherapy (CBT)
All guidelines recommend this above meds
BUT only 50% of people improve
Big push to increase this rate above 50%

6. Fear Conditioning Models
A prevailing model of trauma is that fear conditioning occurs during and after trauma
These models arise from earlier animal models of classical conditioning

7. Classical Conditioning
Learning that certain environmental stimuli predict harmful events.
light + shock
Training
Light alone
Testing
FEAR
Freezing
Potentiated Startle
Heart Rate
Blood Pressure
Stress Hormones

8. Fear Conditioning Models
Trauma = Unconditioned Stimulus
Fear = Unconditioned Response
Reminders = Conditioned Stimuli
Reexperiencing = Conditioned Response

9. Neurobiology of conditioned fear
AMYGDALA
Basolateral
Central CS
Sounds
Smells
Images
Tactile sensations
Fear Expression
Freezing
FPS
Heart Rate
Avoidance
Arterial Pressure
CR = FEAR
CS-US US
Pain
Discomfort
Illness
The formation & storage of fear memories are mediated by the amygdala.
The amygdala mediates a central state of fear.

10. Extinction Learning
Refers to new learning that inhibits initial fear conditioning
Rats learn that the light is safe after repeatedly experiencing it without the shock

11. Extinction Learning
For most of us, we undergo extinction learning in the weeks/months after trauma
We learn that the threat is over and we have new experiences that inhibit initial fear responses

12. Trajectory of PTSD
Weeks After Trauma

13. PTSD = Failed Extinction

14. Neurobiological Model of PTSD
MPFC
Reduced MPFC Inhibition
on amygdala underlies
hyperreactivity in PTSD
Amygdala

15. Amygdala and Anterior Cingulate
Multiple fMRI studies conducted
Mixed evidence for increased amygdala in response to fear
Robust evidence for decreased anterior cingulate/medial prefrontal cortex in response to fear in PTSD

16. What is the Evidence?

17. Role of Heart Rate
Heart rate at the time of trauma may reflect strength of fear conditioning (via increased sympathetic activation or reduced parasympathetic activation)
Many studies have assessed the role of heart rate shortly after trauma to index relationship with subsequent PTSD)

18. Higher Initial Heart Rates & PTSD
Adults:
Shalev et al. (1998)
Bryant et al. (2000)
Schnyder et al. (2003)
Zatzick et al. (2004)
Bryant et al. (2002)
Bryant et al. (2004)
Children:
Kassam-Adams et al. (2005)
Bryant et al (2006)
Kenardy et al. (2007)

19. Injury Vulnerability Study
Assessed 1150 patients across 4 hospitals in Australia
Assessed in hospital, 3, 12, & 24, & 72 months
Assessed for Axis 1 disorders

20. PTSD and Acute Heart Rates
Bryant et al., 2008, J Clin Psychiatry

21. PTSD and Acute Respiratory Rate
Bryant et al., 2008, J Clin Psychiatry

22. Panic Attacks in Acute Stress Disorder
Nixon & Bryant, Beh Res Ther, 2003

23. Psychiatric Disorders at 12 Months

24. Fear Circuitry& Heart Rates After Trauma
Bryant et al., 2009, Psych Med

25. Likelihood of Disorder with Elevated Heart Rate
PTSD: 2.29*
Panic Disorder: 2.81*
Agoraphobia: 2.36*
Social Phobia: 2.94*
OCD: 1.11
GAD: 1.06
MDD: 1.13

26. Acute Morphine & PTSD Morphine attenuates norepinephrine production
Morphine limits fear conditioning in rats
We hypothesized that acute morphine in patients may limit PTSD development

27. PTSD & Morphine Dose
Bryant et al., 2009, Biol Psychiatry

28. Fear Conditioning & Risk Factors
Fear conditioning models can explain other findings following trauma
Huge debate in context of Iraq/Afghanistan regarding role of mild brain injury and PTSD
We assessed risk for disorder after mild brain injury

29. Psychiatric Disorder & MTBI
Bryant et al., 2010, Am J Psychiatry

30. PTSD: 1.57* MDD: 1.38 Agoraphobia: 1.50 Panic Disorder: 1.34
Adjusted Odds Ratio of Developing a Psychiatric Disorder if MTBI Present (controlling for ISS, Trauma Type)
PTSD: *
MDD:
Agoraphobia: 1.50
Panic Disorder: 1.34
Social Phobia: 1.71*
GAD: *
Any Disorder: 1.50

31. Possible Mechanism:
Much evidence that PTSD characterized by impaired medial prefrontal cortex
This network critical in regulating emotions
Damage to prefrontal networks common in MTBI
This may render patients vulnerable to emotional disorders
Bryant, 2008, New Eng J Med

32. Role of Sleep Impairment
We assessed sleep functioning in the 2 weeks prior to injury
Bryant et al., 2010, Sleep

33. PTSD: 2.56 MDD: 2.17 Agoraphobia: 3.40 Panic Disorder: 4.07
Adjusted Odds Ratio of Developing a Psychiatric Disorder if Prior Sleep Disturbance
PTSD:
MDD:
Agoraphobia: 3.40
Panic Disorder: 4.07
Social Phobia: 2.19
OCD:
MDD:

34. Possible Mechanism Sleep loss impedes extinction learning in humans
Sleep loss associated with decreased mPFC connectivity and increased amygdala
Sleep loss prior too trauma may impede neural networks required for extinction

35. Delayed-Onset PTSD Trajectories of PTSD are complex
Delayed-onset PTSD refers to PTSD that commences 6 months after trauma
Redefined in DSM-5
We identified those who had no PTSD at 3 months and compared them to those who had some PTSD at 3 months …. what was the relationship to PTSD at 24 months

36. Predictors of PTSD Severity at 24 Months
No PTSD at 3 Months
PTSD at
3 Months
Gender -
Prior Dx X
Initial Heart Rate
MTBI
Type of Trauma
Baseline PTSD Severity
Days in Hospital
Number of Stressors Since Trauma

37. Changing PTSD Status

38. Trajectories of PTSD

39. Why Do Only Some People Develop PTSD?
An outstanding issue in the field is why do only some people develop PTSD?
Conditioning models would suggest that all people should be conditioned
But only a minority develop PTSD
There is a need for assessment of people before trauma exposure to determine risk factors

40. A Prospective Study of Firefighters
To determine risk factors, we assessed 85 firefighters during cadet training PRIOR TO TRAUMA EXPOSURE
Assessed on startle & conditioning/extinction paradigm
We then assessed them within 12 months of trauma exposure

41. Participant Characteristics
Pretrauma: n = 85 No PTSD
1 month: n = 71 No PTSD
6 months: n = 70 No PTSD
4 Years: n = % PTSD

43. Startle Paradigm
Administered 15 consecutive auditory tones
100DB
Measured SCR & EMG response

44. What Predicts Acute Stress?
Guthrie & Bryant, 2005 Am J Psychiatry

45. Conditioning/Extinction Paradigm
CS +
CS-

46. Extinction Learning Predicts Posttraumatic Stress (6 months)
Guthrie & Bryant, 2006, Psychosom Med

47. Injury Patients are not Random
Much evidence that injured patients have greater trauma histories
Prior trauma increases risk for injury
Further, history of mental disorder increases risk for injury (intentional and unintentional)
63% of our sample had psych history (MUCH higher than population rate)

48. Risk Factors Extinction learning involves mPFC in animals and humans
We studied 250 individuals with structural MRI
Those who suffered early life stress (e.g., child abuse) had small anterior cingulate
ACC implicated in emotion regulation
Cohen et al., 2006, Biol Psychiatry

49. Risk Factors
Possible that structural deficits predispose some of us to negative responses to trauma
These predispositions may result from genetic or early life stress events
May contribute to subsequent exposure to injuries, accidents, traumas
Diathesis-stress process may result in inadequate management of fear if we are exposed to trauma

50. What About Treatment?

51. Cognitive Behaviour Therapy
Based on exposure therapy
Proximity to reminders and learning that they not dangerous
Aims to achieve extinction learning

52. Do Brain Regions Involved in Extinction Learning Predict Response to CBT?

53. Structural MRI 13 PTSD participants had structural MRI
Then received 8 sessions of CBT
Bryant et al., 2008, J Psychiatry & Neuroscience

55. Structural MRI
Size of rostral ACC significantly predicted treatment response (even controlling for initial PTSD severity)
Consistent with animal and human studies of this region underpinning extinction learning

56. Can fMRI Predict Response to CBT?

57. Fear Face Paradigm
Participants viewed subliminal presentation of fearful faces and neutral faces during fMRI (n = 14)
Given 8 session of CBT
Bryant et al., 2008, Psychol Med

59. Results
Bilateral activation of amygdala predicted poor treatment response
CBT requires management of anxiety elicited during therapy
Maybe people who cannot manage anxiety (reflected in amygdala activation) don’t use CBT well

60. Genetics & Treatment Outcome: 5HTT
Short allele of 5HTT reduces serotonin expression
Short allele linked to (a) anxiety, (b) PTSD, (c) excessive amygdala response to fear, & (d) fear conditioning
Does it influence response to CBT?

61. Genetics & Treatment Outcome: 5HTT
45 PTSD patients treated with CBT
DNA obtained
Focused on short/long allele

62. Treatment Response in 5HTT
Bryant et al., 2009 Biol Psychiatry

63. Genetics & Treatment Outcome: BDNF
BDNF mediates LTP & involved in associative learning
BDNF depletion = poor extinction
Injecting BDNF into IL PFC enhances extinction
BDNF Met allele = reduced secretion of BDNF
Carriers of Met allele = reduced MPFC activation during extinction learning

64. Genetics & Treatment Outcome: BDNF
65 PTSD patients treated with CBT
DNA obtained
BDNF measured

65. Treatment Response in BDNF
Felmingham et al, under review

66. Can CBT Enhance
Extinction Networks?

67. Fear Face Paradigm
Participants viewed fearful faces and neutral faces during fMRI (n = 8)
Given 8 session of CBT
Re-scanned 6 months after treatment (n = 8)
Felmingham et al. (2007), Psych Science

69. Results
A significant negative correlation between change in total CAPs score and right rostral ACC activity from pre to post-treatment (r = -.8, p<.01)
This suggests that as PTSD reduces, rostral ACC activity increases

70. Emotion Regulation Training
Exposure elicits distress
One possible strategy is to manage this distress more efficiently
Preparing patients to manage their distress prior to exposure may enhance treatment
Types of trauma focused therapy?
Talk a bit about Cloitre’s study.

71. Therapy CBT CBT + Skills Sx 1: Psychoeducation
Sx 2-5: Review week. Non-directional input.
Sx: 6 CT, IE introduced
Sx 7: IV introduced
Sx 8-11: CT, IE, IV
Sx 12: Relapse Prevention
Sx 1: Psychoeducation Sx 2-5: Emotion Regulation Training Sx: 6 CT, IE introduced Sx 7: IV introduced Sx 8-11: CT, IE, IV Sx 12: Relapse Prevention
Clinical Psychologists
12 once-weekly sessions

72. Types of Emotional Regulation Training
Emotional Tolerance
Breathing retraining
Panic Management
Anger Management
67% emotional tolerance
34% breatihng retraining
26% PMR
Panic
14%
Anger 10%
Depression (activity scheduling) , substance use (urge surfing) modules also options
Audio of therapy rated by 5 independent CBT clinicians
No CBT participants received any emotional regulation components

73. Treatment Retention
CBT and CBT/Skills had comparable pre-exposure sessions
CBT/Skills (M = 5.97) had more exposure sessions than CBT (M = 4.24) participants
67% emotional tolerance
34% breatihng retraining
26% PMR
Panic
14%
Anger 10%
Depression (activity scheduling) , substance use (urge surfing) modules also options
Audio of therapy rated by 5 independent CBT clinicians
No CBT participants received any emotional regulation components

74. CAPS (PTSD)

75. Follow-Up Between Condition Effect Sizes
CAPS
.43*
BDI
.22
BAI
.38*
PTCI-World
.12*

76. Distress Rating Session CBT CBT/Skills 1 61 66 2 65 63 3 68 4 69 71 567 6 72 7 49 8 55 9 51 10 57 60 11 54 46 12 50 35

77. Conclusions
Preparing people with PTSD using Emotional Regulation Training resulted in:
(a) less dropout,
(b) greater reduction in PTSD, anxiety, negative thinking about the world

78. Summary
Psychological factors can lead to marked rehab obstacles and disability
Occurs as result of pre-existing, trauma-related, and ongoing problems
Effects go beyond PTSD
Identifying who needs help is a key barrier
Treatments that address the range may be needed