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Neurobiology, Diagnosis & Treatment of PTSD & TBI in Veterans
1. Diana Glendinning, Ph.D.
Department of Neuroscience and Cell Biology
Rutgers, Robert Wood Johnson Medical School
Anthony Tobia, MD
Department of Psychiatry
Rutgers, Robert Wood Johnson Medical School
Mei T. Liu, Pharm.D., BCPP
Department of Psychiatry, Jersey City Medical Center
Neurobiology, Diagnosis and Treatment of
Post-traumatic Stress Disorder and TBI in
Veterans
5. Post-traumatic Stress Disorder
An estimated 7.7 million U.S. adults have PTSD during
any given year. This may arise from any type of
traumatic experience.
Lifetime prevalence of 8-10%
Females are at higher risk for PTSD (10% vs. 5%)
PTSD can occur at any age
Trauma history increases vulnerability
Individual history increases vulnerability
US Department of Veterans Affairs:
http://www.ptsd.va.gov/professional/PTSD-overview/epidemiological-facts-ptsd.asp
6. Estimated Lifetime prevalence in Veterans: about 30%
of men and women who have spent time in a war zone
experience PTSD.
Estimates by war:
• 23% of Veterans of the Operation Enduring Freedom/Operation
Iraqi Freedom *
• 10% from the Gulf War
• 30% of Vietnam Veterans
Prevalence of PTSD in Veterans
*
8. TBI/PTSD Link and the Military*
• TBI: 19% of all those returning from Iraq
• 44% of returnees from Iraq who reported TBI with LOC
and post concussive symptoms 3 to 4 months after re-
deployment met criteria for PTSD
• 27% with altered consciousness met criteria for PTSD
• 16% with other injuries met criteria for PTSD
• 9% with no injuries met criteria for PTSD
* Hoge C et al. (2008) Mild Traumatic Brain Injury in U.S. Soldiers Returning from Iraq. New Eng J of Med 358(5): 453-63
9. Diana Glendinning, Ph.D.
Department of Neuroscience and Cell Biology
Rutgers, Robert Wood Johnson Medical School
Neurobiology of
Post-traumatic Stress
Disorder
13. Emotional-fear learning occurs in the amygdala.
The hippocampal formation stores other features of
memory (spatial features, environment)
Sensory inputs
FEAR
Trauma or Pain
Stress
26. Rutgers, The State University of New Jersey
Posttraumatic Stress Disorder
Anthony Tobia, MD
Associate Professor
Department of Psychiatry
Rutgers Robert Wood Johnson Medical School
28. Pretraumatic Factors
Female gender
Family history of mental disorder
Younger adult age at the at time
of trauma
Children and adolescents have
lower rates1
Childhood emotional problems by
6 years of age
Premorbid mental disorders
Lower SES
Lower intelligence
Lower education
Childhood adversity
Cultural characteristics
Minority/ethnic status
Lack of social support
1. May reflect previous criteria were insufficiently developmentally informed
Bio Psycho Social
29. • Severity of trauma
• Perceived life threat
• Personal injury
• Interpersonal violence
• Dissociation
• Being a perpetrator
• Witnessing atrocities
• Killing the enemy
Peritraumatic Factors (psychosocial)
30. Psychological
• Negative appraisals
• Inappropriate coping
strategies
• Development of ASD
Social
• Subsequent exposure to
cues
• Subsequent adverse life
events
• Financial losses
• Other losses
• Lack of social support
Posttraumatic Factors (psychosocial)
31. Posttraumatic Stress Disorder (PTSD)
http://www.ptsd.va.gov/ DSM-5
Ø Can occur after you
have been through a
traumatic event
(something terrible
and scary that you
see, hear about, or
that happens to you):
Ø Terrorist attack
Ø Combat exposure
Ø Serious accidents
• Exposure to actual or
threatened death,
serious injury or sexual
violence
• Experienced directly,
witnessed or indirectly
32. Posttraumatic Stress Disorder (PTSD)
http://www.ptsd.va.gov/
Ø During a traumatic
event, you think that
your life or others' lives
are in danger.
Ø You may feel afraid or
feel that you have no
control over what is
happening around you.
• How the individual
experienced event no
longer defining
• Removed from DSM
• Peritraumatic social
factor
DSM-5
33. Comorbidity
http://www.ptsd.va.gov/ DSM-5
Ø Feelings of
hopelessness, shame,
or despair
Ø Depression or anxiety
Ø Drinking or drug
problems
Ø Physical symptoms or
chronic pain
Ø Employment problems
Ø Relationship problems,
including divorce
• 80% more likely than
controls” to have
comorbidity
• Co- occurrence of
PTSD and TBI in recent
wards is 48%
35. Reliving the event
(Re-experiencing symptoms)
• You may have bad
memories or
nightmares.
• You even may feel like
you're going through
the event again (this is
called a flashback).
• Dissociative sx such as
nightmares, flashbacks
• Ongoing psychological
distress at exposure
• NE/sympathetic/
physiological reactivity
on exposure
• Thoughts and
memories that are
recurrent, intrusive,
distressing
http://www.ptsd.va.gov/ DSM-5
One or more intrusion:
36. Avoiding situations that remind you of the
event
• You may try to avoid
situations or people
that trigger memories
of the traumatic event.
• You may even avoid
talking or thinking
about the event.
• Avoidance
• External
– People
– Places
• Internal (things)
– Memories
– Thoughts
– Feelings
http://www.ptsd.va.gov/ DSM-5
37. Negative changes
in beliefs and feelings
http://www.ptsd.va.gov/
DSM-5
Two or more:
• The way you think
about yourself and
others may change
because of the trauma.
• You may feel fear, guilt,
or shame.
• Or, you may not be
interested in activities
you used to enjoy.
• Hard time experiencing
positive emotions
• Out of body experience:
Feelings of detachment
• Negative emotional states
• Organism s cognitions about
the cause of trauma distorted
• Recall of important aspects...
• Impaired
• Negative beliefs exaggerated
• Reduced interest (anhedonia)
38. Feeling keyed up
(Hyperarousal)
http://www.ptsd.va.gov/
DSM-5
Two or more arousal:
• You may be jittery, or
always alert and on the
lookout for danger.
• Or, you may have
trouble concentrating
or sleeping.
• Hypervigilance
• Early morning
awakenings
• Reduced concentration
• Outbursts of anger or
irritability
• Exaggerated startle
• Self-destructive
behavior
39. Rutgers, The State University of New Jersey
Don’t avoid honorin’ heroes!!!
42. Cognitive Behavioral Therapy (CBT)
• Most effective treatment for PTSD
• Learn skills to understand how trauma changed your
thoughts and feelings
• Exposure therapy (variant): talk about your trauma
repeatedly until memories are no longer upsetting
• You also go to places that are safe, but that you have
been staying away from because they are related to the
trauma
43. Movement Desensitization and Reprocessing
(EMDR)
• Involves focusing on sounds or hand movements while
you talk about the trauma
44.
45. The Role of the Psychiatrist (biological)
• Guidelines
• The art of medicine
• You are treating a person, not a cookbook
46. Overview
Clinical Focus
Alcohol
or
Substance
Use Disorder
Short-term
(6-8 weeks)
Long-term
(>8 weeks)
No • Clonazepam
• Alprazolam prn
• Paroxetine or
Sertraline1
• Gabapentin or
Lamotrigine
(adjunct)
Yes • Atypical AP (SGA)2
• Antihistamine prn
• Paroxetine or
Sertraline1
• Gabapentin or
Lamotrigine
(adjunct)
1. If first-line agents are ineffective, try Fluoxetine, Venlafaxine (A) or Mirtazapine (B)
2. Off-label use of sedating SGA (Quetiapine or Olanzapine)
47. Rutgers, The State University of New Jersey
Mei T. Liu, Pharm.D., BCPP
Psychiatry Clinical Pharmacist
Jersey City Medical Center
RWJBarnabas Health
Pharmacological Treatment Options
of Post-traumatic Stress Disorder
48. PTSD Treatment
• No evidence of support pharmacological
treatment to prevent ASD or PTSD
• Treatment can be divided into 3 categories:
– Evidence-based psychotherapies
– Evidence-based pharmacotherapies
– Adjunctive or supplemental treatment
VA/DoD Clinical Prac?ce Guideline. Management of Post-Trauma?c Stress
Guideline Summary. Version 2. 2010.
51. PTSD Treatment
Initial
treatment
• Psychotherapy or SSRI or SNRI
• Reassess at 2 – 4 weeks
Step 1
• Access and address adherence
• Increase dose and/or add psychotherapy if
patient is not already on it
• Switch to another SSRI or SNRI and /or add
psychotherapy
• Reassess at 4 – 6 weeks from initial
treatment
VA/DoD Clinical Prac?ce Guideline. Management of Post-Trauma?c Stress Guideline
Summary. Version 2. 2010.
52. PTSD Treatment
Step 2
• Add psychotherapy and/or switch to
mirtazapine
• Reassess at 8 – 12 weeks from initial
treatment
Step 3
• Switch to alternative step 2 or to TCA or
nefazodone or MAOI
• Add psychotherapy
• Reassess at > 12 weeks from initial
treatment
Add prazosin at any ?me for sleep or nightmare
Consider referral to specialty care at any ?me during treatment
53. Pharmacotherapy of co-morbid PTSD and TBI
• Limited evidence to guide treatment in pa?ents
with co-morbid PTSD and TBI
• Issues to consider
– Cogni?ve and other sequelae of TBI that my interfere with
treatment
– Overlapping symptoms between PTSD and TBI
– Tradeoff between adverse effects versus benefit profiles when
treatment for one condi?on can be poten?ally harmful for
another
HowleU JR, Stein MB. Chapter 16. Post-Trauma:c Stress Disorder: Rela:onship to Trauma:c
Brain Injury and Approach to Treatment. Transla?onal Research in Trauma?c Brain Injury. Boca
Raton (FL): CRC Press/Taylor and Francis Group; 2016.
hUps://www.ncbi.nlm.nih.gov/books/NBK326723/
54. Pharmacotherapy of co-morbid PTSD and TBI
• Start with lower doses due to sensi?vity to side
effects in pa?ent with TBI
• Standard approach in using an?depressants
• An?convulsants for treatment mood disorders,
impulsive anger, irritability, and aggression
• Use low dose an?psycho?cs for psycho?c symptoms
– May help with reexperiencing and hyperarousal
Tanev et al. Brain Injury 2014;28(3):261-270.
55. Pharmacotherapy of co-morbid PTSD and TBI
• S?mulants for fa?gue and aUen?on problems
– May worsen hyperarousal in PTSD
• Medica?ons that may cause cogni?ve deficit
associated in TBI
– An?psycho?cs, an?convulsants, anxioly?cs, and an?cholinergic
medica?ons
• Monitor for adverse effects such as sleep
disturbances, seizures, gait and balance problems,
and deficits in sensory processing
HowleU JR, Stein MB. Chapter 16. Post-Trauma:c Stress Disorder: Rela:onship to Trauma:c
Brain Injury and Approach to Treatment. Transla?onal Research in Trauma?c Brain Injury.
Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016.
hUps://www.ncbi.nlm.nih.gov/books/NBK326723/
McAllister TW, Zafonte R, et al. Neuropsychopharmacology 2016;41:1191-1198.