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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress SUMMARY On August 2, 1990, Iraq invaded Kuwait, and Operation Desert Storm was launched on January 16, 1991, with an air offensive to liberate Kuwait. On February 24, 1991, the ground war began; by February 28, the war was over, and a ceasefire was signed in April. All U.S. troops who had participated in the ground war had returned home by June 13. About 697,000 U.S. military personnel were deployed to the Persian Gulf during the buildup and the war. Most of them were active-duty military personnel, but 261,871 reservists were called to active duty, and 106,047 of them were deployed to the gulf. The United States is once again engaged in a military conflict in the Middle East. Operation Enduring Freedom (OEF) began on October 7, 2001, in response to the September 11, 2001, terrorist attacks on the United States. Troops are stationed in and around Afghanistan, Southwest Asia, and other locations for military and humanitarian purposes. Operation Iraqi Freedom (OIF) began on March 19, 2003, when U.S.-led coalition forces invaded Iraq. As of November 4, 2006, about 1.4 million U.S. troops had been deployed to the conflicts in OEF and OIF. In response to the growing concern about the physical and psychologic health of the Gulf War veterans from the 1990-1991 conflict, Congress passed two laws in 1998: PL 105-277, the Persian Gulf War Veterans Act, and PL 105-368, the Veterans Programs Enhancement Act. Those laws directed the secretary of veterans affairs to enter into a contract with the National Academy of Sciences (NAS) to review and evaluate the scientific and medical literature regarding associations between illness and exposure to toxic agents, environmental or wartime hazards, and preventive medicines or vaccines in members of the armed forces who were exposed to such agents. PL 105-277 also gave NAS permission to identify “other agents, hazards, or medicines or vaccines to which members of the Armed Forces may have been exposed.” In 1996, the Presidential Advisory Committee on Gulf War Veterans’ Illnesses found that stress was an important contributor to those veterans’ illnesses and encouraged the government to continue its research on stress-related disorders. In response to the above laws, the Institute of Medicine (IOM) has had a program to examine health risks posed by specific agents and hazards to which Gulf War veterans might have been exposed during their deployment. Four reports have examined health effects related to depleted uranium, pyridostigmine bromide, sarin, and vaccines; insecticides and solvents; fuels, combustion products, and propellants; and infectious diseases. A fifth report by IOM evaluated the current health status of Gulf War-deployed veterans compared with their nondeployed counterparts. In recent years, the charge to IOM has been expanded to include not only veterans of the 1990-1991 Gulf War but veterans returning from OEF and OIF. Many of the biologic and
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress chemical exposures and their possible health effects have been considered in previous IOM reports, but the health effects associated with deployment-related stress had yet to be considered. A recent IOM report, Gulf War and Health, Volume 4: Health Effects of Serving in the Gulf War, reviewed the health status of Gulf War-deployed veterans. That report found that veterans of the Gulf War report higher rates of nearly all symptoms than their nondeployed counterparts; a higher prevalence not only of individual symptoms but of chronic multisymptom illnesses was also found among Gulf War-deployed veterans. Multisymptom-based medical conditions reported to occur more frequently among deployed Gulf War veterans include fibromyalgia, chronic fatigue syndrome, and multiple chemical sensitivity. The literature also demonstrates that deployment places veterans at increased risk for symptoms that meet diagnostic criteria for a number of psychiatric illnesses, particularly posttraumatic stress disorder (PTSD), anxiety disorders, depressive disorders, and substance abuse. In light of the 1991 Gulf War and the nature of OEF and OIF, the Department of Veterans Affairs (VA) requested that IOM comprehensively review, evaluate, and summarize the peer-reviewed scientific and medical literature regarding the association between deployment-related stress and long-term adverse health effects in Gulf War veterans. In response to VA’s request, IOM appointed the Committee on Gulf War and Health: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress to conduct the review. COMMITTEE’S INTERPRETATION OF ITS CHARGE Given the committee’s charge from VA—to assess the long-term health effects of deployment-related stress—the committee began by defining the deployment in question as “deployment to a war zone.” Combat is one of the most potent stressors that a person can experience, but as military conflicts have evolved to include more guerilla warfare and insurgent activities, restricting the definition of deployment-related stressors to combat may fail to acknowledge other potent stressors experienced by military personnel in a war zone or in the aftermath of combat. Those stressors include constant vigilance against unexpected attack, the absence of a defined front line, the difficulty of distinguishing enemy combatants from civilians, the ubiquity of improvised explosive devices, caring for the badly injured or dying, duty on the graves registration service, and being responsible for the treatment of prisoners of war. Deployment stressors associated with armed conflict include not only combat stressors but noncombat stressors. Non-combat-related stressors that might be experienced by deployed personnel are separation from family, friends, and colleagues; loss of or reduction in income; and concern over employment status when deployment ends. Therefore, the committee considered that military personnel deployed to a war zone, even if direct combat was not experienced, have the potential for exposure to deployment-related stressors and that the emotional and physical reactions of military personnel to those stressors can vary widely. COMMITTEE’S APPROACH TO ITS CHARGE The committee’s charge was the comprehensive review, evaluation, and summary of the peer-reviewed scientific and medical literature regarding the association between deployment-related stress and long-term adverse health effects in Gulf War veterans. Specifically, the committee was to study the physiologic, psychologic, and psychosocial effects of stress. Noted in
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress the committee’s charge is that the study’s findings are applicable not only to veterans of the 1991 Gulf War but to veterans of OEF and OIF. To evaluate associations between deployment-related stress and adverse effects, the committee considered all studies that identified health effects found in military personnel deployed to a war zone. Deployment to a war zone would be used as a surrogate for deployment-related stress. The potential health effects considered included not only physiologic effects but psychologic effects, such as depression and PTSD, and psychosocial effects, such as marital conflict and incarceration. The committee also considered studies of deployed veterans with combat-related PTSD and associated health effects because PTSD can result only after exposure to a traumatic stressor and a war zone is rife with potentially traumatic events. In conducting its deliberations, the committee considered studies of veterans of World War II, the Korean War, the Vietnam War, the 1991 Gulf War, and OEF and OIF. The committee sought to characterize and weigh the strengths and limitations of the available evidence regarding the association between deployment to a war zone and specific adverse health effects. The English-language scientific literature was searched to identify health effects in military veterans from World War II to the conflicts in Afghanistan and Iraq. Although most of the literature focused on U.S. military veterans, veterans from other countries were included. Over 3000 potentially relevant references were retrieved and assessed. The committee used only peer-reviewed published literature as the basis of its conclusions. Committee members read each study critically and considered its relevance and quality. The committee did not collect original data, nor did it perform any secondary data analysis. The committee also did not address policy issues—such as decisions regarding compensation, potential costs of compensation, or any broader policy implications of its findings—nor did it examine treatment approaches for any health effects. EVALUATION CRITERIA When the committee had obtained the studies that met its inclusion criteria, it was necessary to establish which papers would constitute the foundation of its conclusions. In its review of the literature, the committee divided the available studies into two categories: primary and secondary. Primary Studies The committee used primary studies as the basis of its evaluation and conclusions. A primary study demonstrates rigorous methods; for example, it includes details of its methods, has an appropriate control or reference group, has a sample size of at least 100, has the statistical power to detect effects, and includes reasonable adjustments for confounders. Ideally, it has information regarding a specific health effect and exposure. To consider a study as primary, the committee insisted that the health effect be diagnosed or confirmed by a clinical evaluation, specific laboratory test, hospital records, or other medical record or, for a psychiatric outcome, by standardized interviews. Primary studies included comparisons of veterans deployed to a war zone with their nondeployed counterparts and studies that evaluated health effects in veterans with deployment-related or combat-related PTSD.
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress Secondary, or Support, Studies Secondary studies were less rigorous in their methods; for example, a study might have a small sample, not include a physician’s examination or other appropriate evaluation method, or rely only on veterans’ self-reports of symptoms or diseases. They might have been population-based surveys of veterans’ responses to mailed questionnaires. The committee used those types of studies to support findings based on primary studies. CATEGORIES OF ASSOCIATION The committee agreed to base its conclusions on the categories of association that have been used by previous Committees on Gulf War and Health and other IOM committees that evaluated vaccine safety, effects of herbicides used in Vietnam, and indoor pollutants related to asthma. The categories are described below. Sufficient Evidence of a Causal Relationship Evidence is sufficient to conclude that there is a causal relationship between deployment to a war zone and a specific health effect in humans, and the evidence is supported by experimental data on humans or animals. The evidence fulfills the guidelines for sufficient evidence of an association (below) and satisfies several of the guidelines used to assess causality: strength of association, dose-response relationship, consistency of association, and temporal relationship. Sufficient Evidence of an Association Evidence is sufficient to conclude that there is an association; that is, a consistent association has been observed between deployment to a war zone and a specific health effect in human studies in which chance and bias, including confounding, could be ruled out with reasonable confidence. For example, several high-quality studies report consistent associations, are sufficiently free of bias, and include adequate control for confounding. Limited but Suggestive Evidence of an Association Evidence is suggestive of an association between deployment to a war zone and a specific health effect in human studies, but the body of evidence is limited by the inability to rule out chance and bias, including confounding, with confidence. At least one high-quality study reports a positive association that is sufficiently free of bias and includes adequate control for confounding, and other corroborating studies provide support for the association but are not sufficiently free of bias, including confounding. Alternatively, several studies of lower quality might show a consistent association, and the results are probably not due to bias, including confounding.
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress Inadequate/Insufficient Evidence to Determine Whether an Association Exists Evidence is of insufficient quantity, quality, or consistency to permit a conclusion regarding the existence of an association between deployment to a war zone and a specific health effect in humans. Limited/Suggestive Evidence of No Association Evidence is consistent in not showing a positive association between deployment to a war zone and a specific health effect after exposure of any magnitude. A conclusion of no association is inevitably limited to the conditions, magnitudes of exposure, and length of observation in the available studies. The possibility of a very small increase in risk after exposure cannot be excluded. LIMITATIONS OF VETERAN STUDIES Few of the studies reviewed by the committee measured combat exposure or the level of stress experienced by military personnel during deployment to a war zone. Even in the studies that did assess combat exposure, using questionnaires or scales, researchers asked whether an exposure occurred (for example, had a soldier fired on the enemy) rather than the degree to which the veteran may have found the experience to be stressful. Few studies attempted to determine the effects of repeated or combined exposures, such as exposure to extreme heat, to chemical protective gear, and to shooting at an enemy. Another limitation of many of the studies was their retrospective design, which resulted in an inability to distinguish whether a health effect existed before or was a consequence of deployment. Further limitations include the use of self-report questionnaires to assess health effects and exposure; such questionnaires can lead to recall bias with regard to exposures or to inaccuracies in reporting health effects. For those reasons, the committee weighted more heavily the studies that included an examination by a health professional or other appropriate evaluation method. Similarly, for psychiatric disorders, such as PTSD, some studies relied only on symptom checklists to indicate the presence of the disorders rather than on a proper diagnostic examination by a health professional. Many studies had a selection bias in that health effects were assessed in veterans who were in treatment groups, such as inpatients or outpatients at PTSD clinics, or were selected from registries of veterans established by VA. In addition, sufficient time might not have passed since deployment to detect the development of some health outcomes, for example, cancer or heart disease, particularly in OEF and OIF veterans. DEPLOYMENT-RELATED STRESSORS Exposure to combat has been described as one of the most intense stressors that a person can experience; for many people, combat is the most traumatic event of their life. Deployment stressors in the Persian Gulf War included being in the vicinity of a Scud missile explosion, contact with prisoners of war or dead animals, direct combat duty, witnessing the death of a person, being exposed to dismembered bodies or maimed soldiers, coming under small-arms fire, having artillery close by, and fear of being wounded. It was found that military personnel in the Gulf War were at greatest risk for stress when their work was hazardous and
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress they anticipated exposure to chemical warfare; the risk increased with time spent in the field and exposure to the dead and wounded. Another stressor was the feeling that they were deserting their families at a time of need. In OEF and OIF, many of the stressors are more reminiscent of the Vietnam War than of the 1991 Gulf War or World War II. With the defeat of the Iraqi Army and later sectarian violence, U.S. troops have been subjected to guerilla warfare and terrorist actions from civilian insurgents and militias, particularly the use of improvised explosive devices. Soldiers must be constantly on guard, and all civilians must be viewed with caution. Department of Defense (DoD) surveys of Army soldiers and Marines stationed in Iraq found that exposure to combat was the critical determinant of a soldier’s or Marine’s mental health. THE STRESS RESPONSE A person exposed to a stressor, deployment-related or not, may experience a stress response. The word stress is used in many contexts and has a variety of meanings. It is often used to describe a situation characterized by real or perceived threats, but it is also commonly used to refer to the body’s response to such threats. Thus, stress has been used both to describe the environmental events (the stressors) that trigger responses and to refer to the resulting changes (stress response) that occur in the brain and the rest of the body. The stress response is a coordinated set of interactions among multiple organ systems in the body, including the brain, gut, heart, liver, immune system, thyroid, adrenals, pituitary, gonads, bone, and skin. In response to a stressor, the body initiates an acute stress response. Acute stress responses are usually adaptive, preparing the body for “fight or flight.” After exposure to the stressor has ended, the acute stress response subsides, and the body returns to its normal state. However, if the body’s reactions persist after the stressor has ended, a chronic stress response can develop, which can be maladaptive and result in feelings of anxiety and lack of control and chronic health effects. Stressors can also lead to adverse psychosocial effects—such as marital conflicts and homelessness—concurrently with or after the development of health effects. Whether the stress response leads to adverse health effects either in the short term (hours to days) or in the long term (months to years) is determined by a number of factors, including the intensity and duration of the stressful experience, the effects of previous stressors, and risk factors (such as genetic susceptibility or a history of a psychiatric disorder) and protective factors (such as military training or supportive family and social environment). Thus, each person’s response to stress can be modified on the basis of the specific deployment-related stressors, the complex nature of the stress response, and risk and protective factors. POSTTRAUMATIC STRESS DISORDER It is widely recognized that soldiers can suffer psychologic consequences during and after combat. After the Vietnam War, research demonstrated that many veterans, particularly those exposed to severe war-related trauma, and such other traumatized populations as Holocaust survivors, suffered from chronic psychologic problems that often resulted in social and occupational dysfunction. The constellation of symptoms that has come to be known as PTSD is an anxiety disorder whose occurrence is precipitated by exposure to a traumatic event. PTSD
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress was formally recognized as a psychiatric diagnosis in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), published in 1980. Characterized by symptoms of hyperarousal, numbing or avoidance, and re-experiencing of the traumatic event, PTSD may be evident shortly after exposure to a traumatic event or may take years for the veteran to have sufficient symptoms to meet the diagnostic criteria; once developed, the symptoms may persist for many years. PTSD, or symptoms associated with it, has been reported in veterans of World War II, the Korean War, the Vietnam War, the Gulf War, and OEF and OIF. The prevalence of PTSD in veterans increases as combat exposure increases, in some cases showing a dose-response relationship. PTSD is also highly comorbid with other psychiatric disorders, particularly major depression, general anxiety, and substance-use disorders. The presence of comorbid disorders increases the difficulty of diagnosing PTSD. PTSD is also associated with increased reporting of symptoms, medical conditions, and poor health in veterans. The DSM-IV requires that a diagnosis of PTSD include “clinically significant distress and/or impairment in social, occupational, and/or other important areas of functioning.” Veterans with PTSD report more disability and impaired functioning than those without PTSD. Although military personnel may be exposed to identical stressors during their deployment to a war zone, their short-term and long-term responses to those stressors will vary. The variation is due to a host of individual risk factors and protective factors that influence the likelihood of long-term health effects after the exposures. The committee found that combat and being physically wounded were among the most significant risk factors for PTSD or other psychiatric disorders. Other important risk factors include childhood maltreatment, the presence of a pre-existing psychiatric disorder, poor social support on returning home, negative coping styles, being a member of a minority group, and lack of hardiness. Protective factors include better education, higher military rank, having a stable family life, and having a sense of control. HEALTH EFFECTS The committee reviewed numerous epidemiologic studies to arrive at conclusions about association. It weighed the strengths and limitations of all the epidemiologic studies and reached its conclusions by interpreting the data in the entire body of reviewed literature. It assigned each health outcome being considered to one of the five categories of association according to the specific criteria set forth above. The committee also considered health effects of PTSD. Its findings about the strength of the associations between deployment to a war zone, as a surrogate for deployment-related stress, and various health effects are summarized in Table S-1. SUMMARY OF CONCLUSIONS Table S-1 provides a summary of the committee’s conclusions for each health effect discussed in the report by category of association. No health effects were found for two categories of association, sufficient evidence of a causal relationship and limited/suggestive evidence of no association. Of all the long-term health effects reviewed, the strongest findings were on psychiatric disorders, including PTSD, anxiety, and depression. Alcohol abuse, suicide and accidental death in the early years after deployment, and marital and family conflict also appear to be adverse sequelae of deployment-related stress.
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress The committee found limited but suggestive evidence of an association between deployment-related stress and chronic fatigue syndrome, fibromyalgia and chronic widespread pain, gastrointestinal symptoms, skin disorders, incarceration, drug abuse, and increased symptom reporting, unexplained illness, and chronic pain. Finally, it should be repeated that the committee was charged with reviewing scientific data, not with making recommendations regarding VA policy. TABLE S-1 Summary of Findings Regarding the Association Between Deployment to a War Zone and Specific Health and Psychosocial Effects Sufficient Evidence of a Causal Association Evidence from available studies is sufficient to conclude that there is a causal relationship between deployment to a war zone and a specific health effect in humans. The evidence is supported by experimental data and fulfills the guidelines for sufficient evidence of an association (below). The evidence must be biologically plausible and satisfy several of the guidelines used to assess causality, such as strength of association, dose-response relationship, consistency of association, and temporal relationship. No effects. Sufficient Evidence of an Association Evidence from available studies is sufficient to conclude that there is a positive association. That is, a consistent positive association has been observed between deployment to a war zone and a specific health effect in human studies in which chance and bias, including confounding, could be ruled out with reasonable confidence. For example, several high-quality studies report consistent positive associations, and the studies are sufficiently free of bias and include adequate control for confounding. Psychiatric disorders, including PTSD, other anxiety disorders, and depressive disorders. Alcohol abuse. Accidental death in the early years after deployment. Suicide in the early years after deployment. Marital and family conflict. Limited but Suggestive Evidence of an Association Evidence from available studies is suggestive of an association between deployment to a war zone and a specific health effect, but the body of evidence is limited by the inability to rule out chance and bias, including confounding, with confidence. For example, at least one high-quality study reports a positive association that is sufficiently free of bias, including adequate control for confounding, and other corroborating studies provide support for the association (corroborating studies might not be sufficiently free of bias, including confounding). Alternatively, several studies of lower quality show consistent positive associations, and the results are probably not due to bias, including confounding. Drug abuse. Chronic fatigue syndrome. Gastrointestinal symptoms consistent with functional gastrointestinal disorders, such as irritable bowel syndrome or functional dyspepsia. Skin disorders. Fibromyalgia and chronic widespread pain. Increased symptom reporting, unexplained illness, and chronic pain. Incarceration.
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Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress Inadequate/Insufficient Evidence to Determine Whether an Association Exists Evidence from available studies is of insufficient quantity, quality, or consistency to permit a conclusion regarding the existence of an association between deployment to a war zone and a specific health effect in humans. Cancer. Diabetes mellitus. Thyroid disease. Neurocognitive and neurobehavioral effects. Sleep disorders or objective measures of sleep disturbance. Hypertension. Coronary heart disease. Chronic respiratory effects. Structural gastrointestinal diseases. Reproductive effects. Homelessness. Adverse employment outcomes. Limited/Suggestive Evidence of No Association Evidence is consistent in not showing a positive association between deployment to a war zone and a specific health effect after exposure of any magnitude. A conclusion of no association is inevitably limited to the conditions, magnitudes of exposure, and length of observation in the available studies. The possibility of a very small increase in risk after deployment cannot be excluded. No effects. RECOMMENDATIONS The committee recommends that DoD conduct predeployment and postdeployment screening for medical conditions, including psychiatric symptoms and diagnoses, and for psychosocial status to help collect direct evidence about the causal nature of the effects of deployment-related stress. Predeployment screening would also help to identify at-risk personnel who might benefit from targeted intervention programs during deployment and would establish a baseline against which later health and psychosocial effects could be measured after deployment. Postdeployment screening and assessment would provide data that could be analyzed to determine the long-term consequences of deployment-related stress and would allow VA and DoD to implement intervention programs to assist deployed veterans in adjusting to postdeployment life. Such assessments should be made shortly after deployment and should identify those exposures most stressful to the veteran. The assessments should be made at regular intervals thereafter (such as every 5 years) to identify the long-term health and psychosocial effects. The committee further recommends that any longitudinal assessments also be conducted in a representative group of nondeployed veterans to allow appropriate comparisons between deployed and nondeployed veterans regarding health and psychosocial effects.
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