Posttraumatic Stress Disorder: - Geisinger Health System

Posttraumatic Stress Disorder:
Findings from War & Disaster Studies
Joseph A. Boscarino, PhD, MPH
Senior Investigator-II
The Geisinger Center for Health Research
Geisinger Clinic
Danville, PA
July, 2007
PTSD July 2007.ppt

History of Posttraumatic Stress Disorder
(PTSD)
• Symptoms recognized during Civil War
• Shell shock in World War I
• Combat fatigue in World War II
• Combat neurosis in Korean War
• Acute stress reaction in Vietnam War
• PTSD post-Vietnam War in 1980s – DSM-III
• PTSD expanded in 1990s – DSM-IV

Recognition of PTSD post-Vietnam War
• Returning veterans present adjustment
problems/psychopathology
• Veteran advocates label “Vietnam Veteran
Syndrome” (VVS)
• Advocates lobby to have VVS in recognized
• DSM-III committee of APA agreed but required
compromise
• Compromise was it would be called PTSD &
also apply to rape/abuse victims and
others; Incorporated in DSM-III in 1980

PTSD in US Civil War

PTSD Diagnosis in 1994 – DSM-IV
• A1. Exposure to traumatic event (now broadly
defined & subjective)
• A2. Experienced fear, helplessness, horror
• B. Re-experiences traumatic event
• C. Avoid stimuli associated with event
• D. Experiences hyper-arousal symptoms
• E. Duration of symptoms > 1 month
• F. Symptom cause distress or impairment

Prevalence of Traumatic Event Exposure
• Lifetime experience of qualifying
traumatic even in U.S.: 60-90% 1,2,3,4
• Lifetime prevalence of crime/aggravated
assault: 36% 2
• Prevalence higher in recent surveys
using DSM-IV criteria
1. Norris, FH. 1992. J Conslt Clin Psychol, 60:409-418
2. Resnick, H. 1993. J Consult Clin Psychol, 61:984-991
3. Breslau, N. 1998. Arch Gen Psychiatry, 55:626-632
4. Kessler, R. 1995. Arch Gen Psychiatry, 52:1048-1060

Prevalence of PTSD
• General population prevalence of PTSD in
U.S.: 7.8-9.2% 1,3
• Women twice as likely as men to have lifetime
PTSD 1
• Conditional risk of PTSD after
sexual/aggravated assault: 20-60% 1,2,3
• Conditional risk of PTSD after community
disaster: 3.7 for men and 5.4% for women 1
1. Kessler, R. 1995. Arch Gen Psychiatry, 52:1048-1060
2. Resnick, H. 1993. J Consult Clin Psychol, 61:984-991
3. Breslau, N. 1998. Arch Gen Psychiatry, 55:626-632

PTSD Stressor Model
Exposure
Trauma Exposure
Acute
PTSD Sx Occur after Exposure
Chronic
Long-term Psychological Distress,
PTSD, Co-morbid PTSD, etc.

PTSD and the Brain

PTSD – Potential
biologic mechanisms affected
Hypthalamic-pituitary-adrenal (HPA) system
- e.g.,Cortisol down-regulation
Sympathetic-adrenal-medullary (SAM) system
- e.g., Catecholamine up-regulation
Autonomic nervous (AN) system:
- e.g., Hyper-reactivity/startle response increased
These alterations may directly/indirectly increase
“allostatic” load and may lead to disease in some
individuals

Findings in 2006: PTSD and health
Many Populations Studied:
Disaster & Terrorism Victims, Veterans,
Sexual & Physical Assault Victims, POWs,
Refugees, Concentration Camp Survivors
Many Health Outcomes Examined:
Mental Health Status, Cardiovascular Disease,
Diabetes, GI Disease, CFS, Musculoskeletal
Disease, Neurological Disorders, Chronic Pain,
Somatic Disorders, Lower Functional Status,
Higher Healthcare Use, Mortality

PTSD Consequences among War-Fighters
Joseph A. Boscarino, PhD, MPH
Senior Investigator-II
The Geisinger Center for Health Research
Danville, PA
PTSD_pres 2006.ppt

Veterans Study References
J.A. Boscarino, S.N. Hoffman SN. Consistent association between mixed lateral preference and
PTSD: Confirmation among a national study of 2,490 US Army Vietnam veterans. Psychosomatic
Medicine 69: 2007, 365-369.
J.A. Boscarino. PTSD and Mortality among US Army Veterans 30 Years after Military Service,
Annals of Epidemiology, 16: 2006, 248-256.
J.A. Boscarino. Posttraumatic Stress Disorder and Physical Illness: Results from
Clinical & Epidemiologic Studies. Annals of NY Academy of Sciences 2004; 1030: 141-153.
J.A. Boscarino, J. Chang. Higher Abnormal Leukocyte and Lymphocyte Counts 20 Years after
Exposure to Severe Stress: Research and Clinical Implications. Psychosomatic Medicine 61: 1999,
378-386.
J.A. Boscarino, J. Chang. Electrocardiogram Abnormalities among Men with Stress-Related
Psychiatric Disorders: Implications for Coronary Heart Disease and Clinical Research. Annals of
Behavioral Medicine 21: 1999, 227-234.
J.A. Boscarino. Diseases among Men 20 Years after Exposure to Severe Stress: Implications for
Clinical Research and Medical Care. Psychosomatic Medicine 59: 1997, 605-614.
J.A. Boscarino. Post-Traumatic Stress Disorder, Exposure to Combat, and Lower Plasma Cortisol
among Vietnam Veterans: Findings and Clinical Implications. Journal of Consulting and Clinical
Psychology 64: 1996, 191-201.
J.A. Boscarino. Post-Traumatic Stress & Associated Disorders among Vietnam Veterans: The
Significance of Combat Exposure and Social Support. Journal of Traumatic Stress 8: 1995, 317-36.

Vietnam Experience Study
(diseases 17 Years Post-discharge; N = 2,490)
48,513 Theater
and Era Veterans
1985-86
From 4.9 Million
1985-86
7,924 Theater Vets
Contacted for Phone
Interview (CR=87%)
7,364 Era Vets
Contacted for Phone
Interview (CR=84%)
2,490 Theater Vets
Underwent Examinations
and Tests (CR=75%)
1,972 Era Vets
Underwent Examinations
and Tests (CR=63%)
CR=Completion Rate

Adjusted Plasma Cortisol Concentrations among
Theater Veterans by Combat Exposure (p for trend

PTSD Biology

Logistic Regression Predicting Abnormal ECG for Veterans by
Current PTSD, Complex PTSD & General Anxiety (N=2,490)
PTSD Complex PTSD GAD
ECG Classification OR OR OR
Q-Wave Infarctions (n=30) 4.6** 2.6* 1.5
Arrhythmias (n=209) 1.9 2.0** 1.5
AV Conduction Def. (n=78) 2.9** 1.7 0.4
Any Abnormal ECG (n=365) 2.0** 1.5* 1.6**
(n=) (54) (124) (123)
*p< 0.10 **p< 0.05
Boscarino & Chang. Annals of Behavioral Medicine 21: 1999, 227-234.

Specific Autoimmune Diseases among
Theater Veterans by Complex PTSD (N=2490)
AD Type
Adjusted*
O.R. (O.R. 95% C.I.) p-value
Rheum. Arthritis 5.2 (2.3-11.9)

Logistic Regression: PTSD and Mixed Handedness
plus High Combat Exposure (N=2490)
Adjusted*
Mixed + High Combat O.R. (O.R. 95% C.I.) p-value
Edinburgh +/- 70 2.5 (1.6-3.7)

PTSD Symptoms by Combat Exposure & Handedness

Clinical Profile of PTSD Cases (n=124)
among Vietnam Veteran Cohort (N=2490)
• T-lymphocytes counts above normal range (p

PTSD, Inflammation & Disease: Pathogenesis of RA

Trauma and Health: Cardiovascular Disease
Vietnam Veterans: Population Study (Boscarino & Chang, 1999)
- Increase abnormal 12-lead ECGs (e.g., Q-wave infarcts)
WW II & Korean Vets: Population Study (Schnurr et al. (2000)
- Increase in physician-diagnosed arterial disease
• Dutch Resistance Vets: Population Study (Falger et al. 1992)
- Increase in reported angina pectoris
• Ex-POWs: Clinical Study (Corovic et al. 2000)
- Increase in abnormal 12-lead ECGs (e.g., Q-wave infarcts)
• Beirut Civil War Civilians: Clinical Study (Sibai et al. 1989)
- Increase in arteriographic coronary artery disease
Chernobyl Disaster: Population Study (Cwikel et al. 1997)
- Increase in reported heart disease
Childhood Trauma: Population Study (Felitti et al., 1998)
- Increase in adult ischemic heart disease based on exam
• Sexual Assault History: Population Study (Golding 1994)
- Increase in cardiovascular disease symptoms

Vietnam Experience Study
(Deaths 30 Years Post-discharge; N = 15,288)
1985-86
2000
7,924 Theater Vets
Contacted for Phone
Interview (CR=87%)
7,924 Theater Vets
Vital Status Determined
(CR > 95%)
48,513 Theater
and Era Veterans
From 4.9 Million
7,364 Era Vets
Contacted for Phone
Interview (CR=84%)
7,364 Era Vets
Vital Status Determined
(CR > 95%)
1985-86
2000
CR=Completion Rate

Profile of Vietnam Theater vs. Era Veterans
(N=15,288)
Variables Theater Era P-value*
PTSD at interview 10.6 2.9

Profile of PTSD Positive vs. PTSD Negative Veterans
(N=15,288)
Variables Negative Positive P-value
Dead at 2000 at follow-up 4.9 11.8

Cox Regression: Mortality among all Veterans
by PTSD Status (Person-years at risk =229,565)
(N=15,288)
Cause of Death
Adjusted*
H.R. (H.R. 95% C.I.) p-value
All cause (n=820) 2.1 (1.7-2.6)

Cox Regression: Mortality among Era Veterans
by PTSD Status (Person-years at risk = 110,553)
(N=7,364)
Cause of Death
Adjusted*
H.R. (H.R. 95% C.I.) p-value
All cause 2.0 (1.3-3.0) 0.001
CVD 1.2 (0.4-3.4) 0.69
Cancer 0.9 (0.3-3.1) 0.92
External** 2.2 (0.9-5.2) 0.073
*Adjusted for race, age, IQ, military history, smoking history.
** External cause = homicide, suicide, drug overdose,
accidents of undermined intent, etc.
Boscarino. Annals of Epidemiology, 16: 2006, 248-256.

Cox Regression: Mortality among Theater Veterans
by PTSD Status (Person-years at risk = 119,453)
(N=7,364)
Cause of Death
Adjusted*
H.R. (H.R. 95% C.I.) p-value
All cause 2.2 (1.7-2.7)

Veteran study conclusions
• Veterans with current PTSD had for years - since acquired
(mostly) from Vietnam combat - hence, could be causative
for in disease
• Vets were “disease free” at service induction and disease
onset was post service, thus causal ordering correct
• Current lymphocyte, cortisol, hormonal & DTH findings
support the presence of “inflammatory” diseases among
the veterans
• Given above & the controls for bias & confounding, is
plausible PTSD-related stress may cause disease among
veterans
• PTSD-behavioral psychopathogenesis is likely an
additional factor for disease burden & cause of death

World Trade Center Disaster Study

Study Contributors
• Joseph Boscarino, PhD, MPH – Study Director
• Richard Adams, PhD
• Charles Figley, PhD
• Sandro Galea, MD, DrPH
• Heidi Resnick, PhD
• Edna Foa, PhD
• Joel Gold, MD
• Michael Bucuvalas, PhD
• David Vlahov, PhD

WTCD Study References
J.A. Boscarino, RE Adams, CR Figley, S Galea, EB Foa. Fear of Terrorism and Preparedness in New York
City 2 Years after the Attacks: Implications for Disaster Planning and Research. J Pubic Health Manag. &
Practice. 12: 2006, 501-509.
J.A. Boscarino, R.E. Adams, C.R. Figley. Worker Productivity and Outpatient Service Use after the September
11 th Attacks. American Journal of Industrial Medicine 49: 2006.
R.E Adams, J.A. Boscarino. Predictors of PTSD and Delayed-PTSD after Disaster: The Impact of Exposure
and Psychological Resources. Journal of Nervous and Mental Disease 194: 2006 485-493.
J.A. Boscarino, R.E. Adams, E. Foa, P. Landrigan. A Propensity Score Analysis of Brief Worksite Crisis
Interventions after the World Trade Center Disaster. Medical Care 44: 2006, 454-462.
J.A. Boscarino, R.E. Adams, S. Galea. Alcohol use in New York after the Terrorist Attacks: A Study of the
Effects of Psychological Trauma on Drinking Behavior. Addictive Behaviors 31: 2006, 606-621.
R.E. Adams, J.A. Boscarino, S. Galea. Social and Psychological Resources and Health Outcomes after a
Community Disaster. Social Science and Medicine 60: 2006, 176-188.
J.A. Boscarino, RE Adams. Disparities in Mental Health Treatment following the World Trade Center Disaster:
Implication for Mental Health Care and Services Research. J Traumatic Stress 18: 2005, 287-97.
R.E. Adams, J.A. Boscarino. Differences in Mental Health Outcomes among Whites, African Americans, and
Hispanics Following a Community Disaster. Psychiatry 68: 2005, 250-265.
R.E. Adams, JA. Boscarino. Stress and Well-being in the Aftermath of the World Trade Center Attack: The
Continuing Effects of Community-wide Disaster. Journal of Community Psychology 32: 2005, 175-190.

WTCD Study References
J.A. Boscarino, R.E. Adams, C.R. Figley. Mental Health Service Use 1-Year after the World Trade
Center Disaster: Implications for Medical Care. General Hospital Psychiatry 26: 2004, 346-358.
D. Vlahov, S. Galea, H. Resnick, J. Ahern, J.A. Boscarino, M. Bucuvalas, J. Gold, D. Kilpatrick.
Increased use of Cigarettes, Alcohol, and Marijuana among Manhattan residents after the
September 11 th Terrorists Attacks. American Journal of Epidemiology 155: 2002, 988-996.
J.A. Boscarino, C.R. Figley, R.E. Adams, S. Galea, H. Resnick, A.R. Fleischman, M. Bucuvalas, J.
Gold. Adverse Reactions of Study Persons recently Exposed to Mass Urban Disaster. Journal
of Nervous and Mental Disease 192: 2004, 515-524.
J.A. Boscarino, S. Galea, R.E. Adams, J. Ahern, H. Resnick, D. Vlahov. Mental Health Service and
Psychiatric Medication Use in New York City after the September 11, 2001, Terrorist Attack.
Psychiatric Services 55: 2004, 274-283.
J.A. Boscarino, C.R. Figley, R.E. Adams. Fear of Terrorism in NY after the September 11 Attacks:
Implications for Emergency Mental Health and Preparedness. International Journal of
Emergency Mental Health 5: 2003, 199-209.
J.A. Boscarino, S. Galea, J. Ahern, H. Resnick, D. Vlahov. Psychiatric Medication Use among
Manhattan Residents following the World Trade Center Disaster. Journal of Traumatic Stress
16: 2003, 301-306.

Previous studies of
persons after disasters
• Most research focused on persons directly
affected
• Few studies examined outcomes in a
large-scale population study
• Major Research Question in Our Study:
Were post-disaster interventions
beneficial?

Study design
• Wave 1 Random-digit-dial phone surveys 1-year
after (N=2,368) –> adults only
• Over-sample of persons who had treatment after
WTC disaster (~ 80%)
• 45-minute mental health/trauma survey used
• Wave 2 phone survey 1-year after W1 (2 years
post-disaster)
• Re-interviewed 71% of W1 respondents in W2
• Wave 1 + Wave 2 longitudinal data = 1,681
persons

Study sampling frame – 5 NYC boroughs
sampled probability proportionate to size
(N = 2,368)

Study measures
• Main Dx and service measures from
National Co-morbidity Study*
• Intervention exposure assessed
‣Determined if respondent attended intervention
after WTC disaster
‣Where sessions were conducted
‣Number of sessions attended
‣Clinical focus of sessions
‣Perceptions of how helpful sessions were
*RC Kessler, et al. The Epidemiology of Major Depression. JAMA 2003;
289: 3095-3105.

Study outcomes measures
• Outcomes assessed:
‣ PTSD past year (DSM-IV)
‣ Depression past year (DSM-IV)
‣ Binge Drinking past year (6+ drinks)
‣ Alcohol Dependency past year (CAGE)
‣ SF-12 functional status
‣ BSI-18: Somatization, Global Severity Index
‣ Worker Productivity
‣ Outpatient mental & health services use
‣ Non-traditional services use.

Sample characteristics of w1 & w2
compared to 2000 U.S. Census for NYC
Characteristics US Census % Weighted W1
Sample %
Age
18-24
13.2
15.2
25-34
22.5
24.0
35-44
20.8
22.2
45-54
16.7
18.7
55-64
11.3
10.0
65+
15.5
9.8
Weighted W2
Sample %
12.7
21.3
22.1
20.3
12.0
11.7
Race
White
African American
Asian
Hispanic
Other
38.7
23.0
10.1
24.7
3.6
39.2
26.3
5.2
25.7
3.5
43.0
26.0
4.6
24.1
2.4

Prevalence of PTSD and Depression in NYC
4 and 12 months after September 11
PTSD/Depression 4 Months (Sx) 12 Months (Dx)
PTSD Ever 15.3 8.2
PTSD Since 9/11 9.1 5.3
PTSD Past 6 months -- 3.4
Depression Since 9/11 7.8 8.2
Peri-Event Panic Attack 16.7 10.8

Mental health service use 1-year before vs.
1-year after disaster in NYC (N=2,368)
Percent
20
15
10
5
Pre-Disaster
Post-Disaster
0
Pysch.
Psychiat.
Other MD
MH Counsel.
Soc. Wrk.
Minister
Self-Help
Boscarino, et al. General Hospital Psychiatry 26: 2004, 346-358.
Any Visits

WTC disaster event exposure
assessment
Rescue Effort
Saw Inperson
Fear of Injury/Death
Relative/Friend Killed
Lost Possessions
Lost Job
8.3%
7.8%
3.2%
33.4%
35.6%
40.7%
JA Boscarino et al. Mental Health Service Use 1-Year after the World Trade Center
Disaster: Implications for Medical Care. General Hospital Psychiatry 26: 2004, 346-358.

Exposure to WTC disaster and
mental health visits/medication use – W1
(all comparisons significant at p

Prevalence of PTSD and depression by
Exposure to WTC disaster - wave 1 (N=2,368)
Percent
20
15
10
5
0
PTDS Past Year
4.9
3.8
Low
Exposure
6.6
4.3
Moderate
Exposure
Depression Past Year
10.9
6.0
High
Exposure
18.4
12.6
(both p

% Increased Drinking by Exposure
to WTC Disaster Events
Increase 2+ Drinks/Day
Increase 2+ Days Drinking
25
20
Increased drinks/day p0.05
15
10
5
0
Low
Exposure
Moderate
Exposure
High
Exposure
Very High
Exposure
Boscarino et al. Alcohol use in NY after the terrorist attack. Addictive Behaviors 2006;31:606-621.

Differences in receiving crisis
interventions at work by demographics
Characteristic
Gender
Male
Female
Race
White
African American
Hispanic
Other
(N=180)
Received
Intervention
(p = ns)
37.7
62.3
(p = ns)
45.7
20.1
27.0
7.2
Boscarino, et al. Medical Care, 2006;44:454-462.
(N=1,501)
No
Intervention
46.8
53.2
42.7
26.4
23.9
7.0

Percent
% Received crisis intervention at
work by exposure to WTC disaster
25
20
15
10
5
0
10% NYC adults had postdisaster
crisis interventions
- 7% had at worksite
1.5
Low
Exposure
Received Intervention
5.4
Moderate
Exposure
11.6
High
Exposure
(p

Number of crisis sessions
received at work – wave 1 (n=180)
17%
44%
One
Two to
Three
Four or
More
39%
Boscarino, et al.
Medical Care 2006;44:454-462.

Log-odds ratio showing positive effect
of counseling at follow-up – covariate adjusted
0.5
Log odds ratios
0
-0.5
-1
-1.5
-2
-2.5
Binge
Alc Dep
Partial PTSD
Depression
Somatization
Anxiety
Global Impair
One
2 to 3
No sessions = reference category
Boscarino, et al. Medical Care 2006;44:454-462.

Delayed PTSD post-WTCD and Percent experiencing 2+
stressful life events in past 2 years
80%
78% 79%
70%
60%
50%
40%
44%
54%
39%
58%
Year 1
Year 2
30%
20%
14%
18%
10%
Resilient
n=1494
Remitters
n=92
Delayed
n=66
Acute
n=28
Adams, Boscarino. Predictors of PTSD & delayed-PTSD after disaster. J Nervous and Mental Disease 2006;194:485-93.`

Delayed PTSD post-WTCD and percent experiencing
Low self-esteem in past 2 years
90%
80%
70%
64%
71%
78%
71%
60%
50%
40%
30%
35%
30%
47%
54%
Year 1
Year 2
20%
10%
Resilient
Remitters
Delayed
Acute
n=1495
n=92
n=66
n=28
Adams, Boscarino. Predictors of PTSD & delayed-PTSD after disaster. J Nervous and Mental Disease 2006;194:485-93.

PTSD and Genetics

Search for Genetics of PTSD

Genetic basis of PTSD
• One-third of PTSD variation due to genetics:
• Serotonin transporter gene (SCL6A4)
• Dopamine transporter & D 2 D 4 receptor genes
• Monamine Oxidase A (MAOA) gene
• Norepinephrine gene
• Neuropeptide Y & Substance P genes
• Neurobiologic factors associated w/ PTSD:
• Mixed lateral handedness
• Lower Intelligence
• ADHD
• NSS

Results of allelic variations for serotonin
transporter gene (SLC6A4) x environmental exposure
(A. Caspi, et al. Science 2003; 301: 386-391)

Current status of PTSD research
• Search for PTSD genes underway
• Advances in PTSD measures being made
• Psychobiology of PTSD emerging
• Impact of PTSD involves other major
psychopathology
• Studies of effectiveness of brief treatments
• Treat PTSD early & prevent disease/death?

Multifactoral PTSD Outcome Model:
Potential Causal Pathways to Disease Outcomes
Heredity & Shared
Environment
Implications
• Multi-level Analyses
• Longitudinal Framework
• Biologic Factors
• Behavioral Analyses
Psych Trauma
Exposure
Health Status
Behavior
Biological
Alterations
PTSD