VOLUME 6
PHYSIOLOGIC, PSYCHOLOGIC, AND PSYCHOSOCIAL EFFECTS OF DEPLOYMENT-RELATED STRESS
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
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Committee on Gulf War and Health: Physiologic, Psychologic, and Psychosocial
Effects of Deployment-Related Stress
Board on Population Health and Public Health Practice
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National
Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National
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were chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract V101(93)P-2155B between the National Academy of Sciences and the
Department of Veterans Affairs. Any opinions, findings, conclusions, or recommendations expressed in this
publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that
provided support for this project.
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Suggested citation:
IOM (Institute of Medicine). 2008. Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial
Effects of Deployment-Related Stress. Washington, DC: The National Academies Press.
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COMMITTEE ON GULF WAR AND HEALTH: PHYSIOLOGIC,
PSYCHOLOGIC, AND PSYCHOSOCIAL EFFECTS OF DEPLOYMENT-
RELATED STRESS
RICHARD MAYEUX, MD, MSc (Chair), Gertrude H. Sergievsky Professor of Neurology,
Psychiatry, and Epidemiology, Sergievsky Center, and Codirector, Taub Institute,
Columbia University
KATHRYN KARUSAITIS BASHAM, PhD, MSW, Professor, Smith College School for
Social Work
EVELYN J. BROMET, PhD, Professor of Psychiatry and Preventive Medicine, State
University of New York at Stony Brook
GREGORY L. BURKE, MD, MSc, Professor and Chair, Public Health Sciences, Wake Forest
University School of Medicine
DENNIS S. CHARNEY, MD, Dean, Anne and Joel Ehrenkranz Professor, Mount Sinai School
of Medicine
MICHAEL DAVIS, PhD, Robert W. Woodruff Professor of Psychiatry, Behavioral Sciences
and Psychology, Emory University
DOUGLAS A. DROSSMAN, MD, Professor of Medicine and Psychiatry and Codirector, UNC
Center for Functional GI and Motility Disorders, University of North Carolina at Chapel
Hill
DWIGHT L. EVANS, MD, Ruth Meltzer Professor and Chair, Psychiatry, and Professor of
Psychiatry, Medicine, and Neuroscience, University of Pennsylvania School of Medicine
VINCENT J. FELITTI, MD, Kaiser Permanente Medical Care Program, San Diego, CA
JANICE L. KRUPNICK, PhD, Professor, Department of Psychiatry, Georgetown University
School of Medicine
WILLIAM B. MALARKEY, MD, Professor of Internal Medicine and Molecular Virology,
Immunology and Medical Genetics and Director, Clinical Research Center, Ohio State
University
BRUCE S. MCEWEN, PhD, Alfred E. Mirsky Professor and Head, Harold and Margaret
Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University
THOMAS G. PICKERING, MD, DPhil, Professor of Medicine, Columbia University
JERROLD F. ROSENBAUM, MD, Psychiatrist-in-Chief, Massachusetts General Hospital, and
Stanley Cobb Professor of Pyschiatry, Harvard Medical School
B. TIMOTHY WALSH, MD, William and Joy Ruane Professor of Pediatric
Psychopharmacology, College of Physicians and Surgeons, Columbia University, and
Chief, Division of Clinical Therapeutics, New York State Psychiatric Institute
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CONSULTANTS
KERRY L. KNOX, PhD, Associate Professor, Department of Psychiatry and Community and
Preventive Medicine, University of Rochester School of Medicine and Department of
Veterans Affairs, Director, VISN 2 Center for Excellence at Canandaigua
CAROL NORTH, MD, VA North Texas Health Care System and Department of Psychiatry,
University of Texas Southwestern Medical Center at Dallas
MIRIAM DAVIS, Independent Medical Writer, Silver Spring, MD
STAFF
CAROLYN FULCO, Scholar
ROBERTA WEDGE, Senior Program Officer
SANDRA GOODBODY, Senior Program Officer
PETER JAMES, Senior Program Associate
DEEPALI M. PATEL, Senior Program Associate
MICHAEL SCHNEIDER, Senior Program Associate
DAVID J. TOLLERUD, Program Assistant
DANIELLE K. STOLL, Program Assistant
DAMIKA WEBB, Research Assistant
RENEE WLODARCZYK, Senior Program Assistant
NORMAN GROSSBLAT, Senior editor
ROSE MARIE MARTINEZ, Director, Board on Population Health and Public Health Practice
HOPE HARE, Administrative Assistant
vi
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REVIEWERS
This report has been reviewed in draft form by persons chosen for their diverse
perspectives and technical expertise in accordance with procedures approved by the National
Research Council’s Report Review Committee. The purpose of this independent review is to
provide candid and critical comments that will assist the institution in making its published
report as sound as possible and to ensure that the report meets institutional standards of
objectivity, evidence, and responsiveness to the study charge. The review comments and draft
manuscript remain confidential to protect the integrity of the deliberative process. We wish to
thank the following for their review of this report:
Elissa S. Epel, Department of Psychiatry, University of California, San Francisco
Manning Feinleib, Department of Epidemiology, The Johns Hopkins University
Edgar Garcia-Rill, Center for Translational Neuroscience, Department of Neurobiology &
Developmental Sciences, University of Arkansas for Medical Sciences
Danny O. Jacobs, Department of Surgery, Duke University Medical Center
Karen A. Matthews, Western Psychiatric Institute & Clinic, University of Pittsburgh School of
Medicine
Eric J. Nestler, Department of Psychiatry, The University of Texas Southwestern Medical
Center at Dallas
William E. Schlenger, Abt Associates, Inc.
Robert D. Sparks, TASER Foundation
Ezra S. Susser, Department of Epidemiology, Columbia University
Daniel S. Weiss, Department of Psychiatry, University of California, San Francisco
Nancy Fugate Woods, School of Nursing, University of Washington
Although the reviewers listed above have provided many constructive comments and
suggestions, they were not asked to endorse the conclusions or recommendations, nor did they
see the final draft of the report before its release. The review of this report was overseen by Dr.
Charles E. Phelps, University of Rochester, and Dr. Harold C. Sox, American College of
Physicians/Annals of Internal Medicine. Appointed by the National Research Council and the
Institute of Medicine, they were responsible for making certain that an independent examination
of this report was carried out in accordance with institutional procedures and that all review
comments were carefully considered. Responsibility for the final content of this report rests
entirely with the author committee and the institution.
vii
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CONTENTS
ACRONYMS............................................................................................................................... xiii
PREFACE ................................................................................................................................... xvii
SUMMARY.....................................................................................................................................1
Committee’s Interpretation of Its Charge ...................................................................................2
Committee’s Approach to Its Charge..........................................................................................2
Evaluation Criteria ......................................................................................................................3
Categories of Association ...........................................................................................................4
Limitations of Veteran Studies ...................................................................................................5
Deployment-Related Stressors ....................................................................................................5
The Stress Response....................................................................................................................6
Posttraumatic Stress Disorder .....................................................................................................6
Health Effects..............................................................................................................................7
Summary of Conclusions ............................................................................................................7
Recommendations .......................................................................................................................9
1 INTRODUCTION ....................................................................................................................11
Demographics ...........................................................................................................................12
Committee’s Interpretation of Its Charge .................................................................................13
Committee’s Approach to Its Charge........................................................................................14
Organization of the Report........................................................................................................15
References .................................................................................................................................16
2 CONSIDERATIONS IN IDENTIFYING AND EVALUATING THE LITERATURE .........17
Identification of the Literature ..................................................................................................17
Types of Evidence.....................................................................................................................18
Inclusion Criteria.......................................................................................................................23
Additional Considerations.........................................................................................................24
Considerations in Assessing the Strength of Evidence .............................................................25
Categories of Association .........................................................................................................26
Limitations of Veteran Studies .................................................................................................28
Summary ...................................................................................................................................28
References .................................................................................................................................29
3 DEPLOYMENT-RELATED STRESSORS .............................................................................31
Stressors During Combat ..........................................................................................................32
Noncombat Stressors.................................................................................................................35
Anticipation of Deployment to a War Zone..............................................................................36
Military Sexual Assault and Harassment ..................................................................................37
Living Conditions .....................................................................................................................38
Environmental and Chemical Stressors ....................................................................................39
Reserve and National Guard Troops .........................................................................................39
Peacekeepers .............................................................................................................................40
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x CONTENTS
Women ......................................................................................................................................41
Conclusions ...............................................................................................................................43
References .................................................................................................................................43
4 THE STRESS RESPONSE.......................................................................................................49
Central Role of the Brain ..........................................................................................................50
Modifiers of the Stress Response..............................................................................................56
Chronic Stress and Health.........................................................................................................59
Conclusions ...............................................................................................................................66
References .................................................................................................................................66
5 POSTTRAUMATIC STRESS DISORDER .............................................................................75
Diagnosis and Clinical Features................................................................................................76
Prevalence .................................................................................................................................78
Course .......................................................................................................................................81
Comorbidity and Disability.......................................................................................................84
Risk and Protective Factors.......................................................................................................86
Neurobiology ............................................................................................................................94
Conclusions .............................................................................................................................100
References ...............................................................................................................................100
6 HEALTH EFFECTS ...............................................................................................................115
Organization of This Chapter..................................................................................................115
Cancer .....................................................................................................................................117
Endocrine Diseases .................................................................................................................133
Psychiatric Disorders ..............................................................................................................142
Substance-Use Disorders ........................................................................................................158
Neurobehavioral and Neurocognitive Effects.........................................................................167
Chronic Fatigue Syndrome .....................................................................................................174
Sleep Disturbances ..................................................................................................................179
Cardiovascular Diseases .........................................................................................................183
Respiratory System Diseases ..................................................................................................197
Digestive System Disorders ....................................................................................................204
Skin Disorders.........................................................................................................................214
Fibromyalgia and Chronic Widespread Pain ..........................................................................222
Reproductive Effects...............................................................................................................229
Suicide and Accidental Death .................................................................................................237
Symptom Reporting ................................................................................................................248
References ...............................................................................................................................261
7 PSYCHOSOCIAL EFFECTS.................................................................................................283
Marital and Family Conflict....................................................................................................283
Homelessness ..........................................................................................................................299
Incarceration............................................................................................................................304
Employment ............................................................................................................................308
References ...............................................................................................................................312
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CONTENTS xi
8 CONCLUSIONS AND RECOMMENDATIONS .................................................................317
Quality of the Studies..............................................................................................................317
Overview of Health Effects.....................................................................................................318
Recommendations ...................................................................................................................321
References ...............................................................................................................................321
INDEX .........................................................................................................................................323
Tables
TABLE S-1 Summary of Findings Regarding the Association Between Deployment to a War
Zone and Specific Health and Psychosocial Effects............................................................8
TABLE 3-1 Combat Experiences Reported by Members of the U.S. Army and Marine Corps
After Deployment to Iraq or Afghanistan............................................................................34
TABLE 3-2 Stressors Experienced by U.S. Forces in the Gulf War...........................................37
TABLE 3-3 Percentage of Active-Duty vs Reserve and National Guard Troops, by War .........40
TABLE 5-1 Prevalence of Traumatic Events and PTSD in Men and Women............................78
TABLE 5-2 Estimated Prevalence of PTSD in U.S. Military Populations .................................82
TABLE 6-1 Cancer ......................................................................................................................128
TABLE 6-2 Endocrine Diseases..................................................................................................141
TABLE 6-3 Psychiatric Disorders ...............................................................................................153
TABLE 6-4 Substance-Use Disorders .........................................................................................164
TABLE 6-5 Neurobehavioral and Neurocognitive Effects .........................................................171
TABLE 6-6 Chronic Fatigue Syndrome ......................................................................................178
TABLE 6-7 Cardiovascular Diseases ..........................................................................................195
TABLE 6-8 Respiratory System Diseases...................................................................................202
TABLE 6-9 Digestive System Disorders.....................................................................................211
TABLE 6-10 Skin Disorders .......................................................................................................220
TABLE 6-11 Fibromyalgia and Chronic Widespread Pain.........................................................228
TABLE 6-12 Reproductive Effects ............................................................................................234
TABLE 6-13 Suicide and Accidental Death................................................................................245
TABLE 6-14 Symptom Reporting...............................................................................................259
TABLE 7-1 Marital and Family Conflict ....................................................................................295
TABLE 7-2 Homelessness...........................................................................................................303
TABLE 7-3 Incarceration ............................................................................................................307
TABLE 7-4 Adverse Employment Outcomes .............................................................................311
TABLE 8-1 Summary of Findings Regarding the Association Between Deployment to a War
Zone and Specific Health and Psychosocial Effects............................................................319
Boxes and Figures
BOX 4-1 Physiologic Changes During the Stress Response .......................................................50
BOX 5-1 DSM-IV Diagnostic Criteria for Posttraumatic Stress Disorder...................................77
BOX 6-1 Case Definition of Chronic Fatigue Syndrome............................................................174
FIGURE 1-1 Schematic depiction of the relationship between deployment to a war zone and
adverse health and psychosocial effects. .............................................................................15
FIGURE 4-1 Stress-response pathways. .....................................................................................52
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xii CONTENTS
FIGURE 4-2 How chronic stress can affect behavior and health................................................55
FIGURE 4-3 Chronicity of stressors............................................................................................57
FIGURE 4-4 The brain-gut axis and IBS. ...................................................................................65
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ACRONYMS
ACTH Adrenocorticotrophic hormone, corticotropin
APA American Psychiatric Association
ASI Anxiety sensitivity index
AUDIT Alcohol use disorder identification test
BIRLS Beneficiary identification record locator subsystem
BNST Bed nucleus of the stria terminalis
BSS Body-system symptom
CAPS Clinician-Administered PTSD Scale
CCEP Comprehensive Clinical Evaluation Program
CDC Centers for Disease Control and Prevention
CES Combat Exposure Scale
CFS Chronic fatigue syndrome
CHD Coronary heart disease
CI Confidence interval
CIDI Composite International Diagnostic Interview
CNS Central nervous system
COPD Chronic obstructive pulmonary disease
CRH Corticotropin-releasing hormone
CSF Cerebrospinal fluid
CSMs Cerebrospinal malformations
CTS Conflict Tactics Scale
CVLT California Verbal Learning Test
DIS Diagnostic Interview Schedule
DMDC Defense Manpower Data Center
DoD Department of Defense
DSM Diagnostic and Statistical Manual of Mental Disorders III or IV
GAD Generalized anxiety disorder
GI Gastrointestinal
HDL High-density lipoprotein
HPA Hypothalamus-pituitary-adrenal
HU13 Health Utilities Index Mark 3
HVVP Hawaiian Vietnam Veterans Project
IBS Irritable bowel syndrome
ICD International Statistical Classification of Diseases and Related Health
Problems
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xiv ACRONYMS
IEDs Improvised explosive devices
IOM Institute of Medicine
km Kilometer
MDD Major depression disorder
MHAT Mental Health Advisory Team
MHM Military History Measure
MMPI Minnesota Multiphasic Personality Inventory
MPI Martial Problem Index
MRI Magnetic resonance imaging
MSAs Metropolitan statistical areas
NART National Adult Reading Test
NAS National Academy of Sciences
NCHS National Center for Health Statistics
NCO Noncommissioned officer
NCS National Comorbidity Survey
NHANES National Health and Nutrition Examination Survey
NHL Non-Hodgkin’s lymphoma
NSVG National Survey of the Vietnam Generation
NVVRS National Vietnam Veterans Readjustment Study
OEF Operation Enduring Freedom
OIF Operation Iraqi Freedom
OR Odds ratio
PASAT Paced Auditory Serial Addition Test
PB Pyridostigmine bromide
PIR Proportional incidence rate
PMR Proportional morbidity ratio
PPI Parental Problem Index
PTSD Posttraumatic stress disorder
RR Relative risk
SCID Structured Clinical Interview for DSM-III or IV
SE Standard error
SF-36 36-Item Medical Outcomes Study Short-Form
T3 Triiodothyronine
T4 Thyroxine
TSH Thyroid-stimulating hormone
UK United Kingdom
UN United Nations
VA Department of Veterans Affairs
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ACRONYMS xv
VES Vietnam Experience Study
VET Registry Vietnam-Era Twin Registry
vs Versus
WAIS-R Wechsler Adult Intelligence Scale-revised
WCST Wisconsin Card Sorting Test
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PREFACE
Deployment to a war zone has a profound impact on the lives of many of the troops who
are deployed to foreign soil and on their family members. Needless to say, numerous stressors
are associated with deployment, from terrifying concerns about surviving, being taken prisoner,
and being tortured to the horrific possibility of seeing friends die, being maimed, and handling
dead bodies. Less traumatic but more pervasive stressors include anxiety about home life, such
as loss of a job and income, impacts on relationships, and absence from family.
The effects of deployment-related stressors on a veteran’s health during and after
deployment are numerous. When sudden and life-threatening stressors are encountered, the body
will typically react with an acute “flight or fight” response that subsides when the stressor goes
away. If the stressor or the acute response persists, the body may react with a more prolonged
stress response that can lead to harmful long-term effects on health. The focus of this report, by
the Institute of Medicine (IOM) Committee on Gulf War and Health: Physiologic, Psychologic,
and Psychosocial Effects of Deployment-Related Stress, is the long-term effects of deployment-
related stress. What happens to military personnel when they are subjected to the many stressors
that occur in a war zone?
The U.S. Department of Veterans Affairs and Congress have secured the assistance of
IOM in evaluating the scientific literature regarding an association between deployment-related
stressors and health effects. Congress’s request regarding the possible association between illness
and exposure to stressors in the Gulf War is similar to its approach after the Vietnam War to
exposure to Agent Orange and after the 1991 Persian Gulf War to exposure to numerous biologic
and chemical agents. Although seemingly straightforward conceptually, this task has proved to
be much more difficult than previous studies. The committee discussed how to define
deployment-related stress, the types of stressors encountered, and how they might be assessed or
measured.
In this report, the committee equated deployment-related stress with being deployed to a
war zone, although it recognized that not everyone deployed to a war zone would respond to
stressors in the same way and that not everyone would necessarily find a particular event
stressful. The reaction to deployment-related stressors would depend on numerous factors that
were present before, during, and after deployment. Stressors that people experienced in
childhood, their interactions with friends and family, and whether they were wounded during
deployment would all play a role in the nature of the response. The committee also understood
that some military personnel would have minor reactions and transient health effects, some
would have severe reactions and more chronic health effects, and some would go on to develop
posttraumatic stress disorder (PTSD), which could be associated with additional health effects.
That approach is detailed in the committee’s report.
The committee deliberated for many months and met 14 times. It reviewed all the studies
of health effects in veterans deployed to a war zone and found that most studies did not measure
the stressors of war (although that was not required for inclusion in the committee’s analysis),
and that the ones that did measure deployment-related stress were most often related to PTSD.
The committee noted that although experimental data from studies in animals indicated
xvii
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xviii PREFACE
numerous health effects associated with various types of stressors, the human literature is much
more challenging to interpret.
I am deeply appreciative of the hard work of our committee members: Kathryn Basham,
Evelyn Bromet, Gregory Burke, Dennis Charney, Michael Davis, Douglas Drossman, Dwight
Evans, Vincent Felitti, Janice Krupnick, William Malarkey, Bruce McEwen, Thomas Pickering,
Jerrold Rosenbaum, and Timothy Walsh, and of our expert consultants Carol North, Kerry Knox,
and Miriam Davis. The committee would like to thank Jack Gorman for his thoughtful input.
Although the committee developed conclusions independently of input from IOM staff, we
deeply appreciate their hard work and attention to detail and the extensive research that they
conducted to ensure that we had all the information that we needed from the outset. It has been a
privilege and a pleasure to work with the IOM staff directed by Roberta Wedge and Carolyn
Fulco. Without them, this report would not have been possible. Most of all, our committee
appreciates the veterans who have served in this country’s wars. It is for them that we do this
work, and we hope that this report will inform those who have given so much to our nation.
Richard Mayeux, MD, MSc (Chair)
Sergievsky Professor of Neurology, Psychiatry, and Epidemiology
Director, Sergievsky Center; Codirector, Taub Institute
College of Physicians and Surgeons
Columbia University