1 Veterans Health Administration, Department of Veterans Affairs, Washington, DC.
2 Veterans Health Administration, Department of Veterans Affairs, East Orange, NJ.
3 Food and Drug Administration, Department of Health and Human Services, Rockville, MD.
Received for publication April 26, 2002; accepted for publication August 19, 2002.
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ABSTRACT |
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fatigue syndrome, chronic; Persian Gulf syndrome; stress disorders, post-traumatic; veterans
Abbreviations: Abbreviations: CFS, chronic fatigue syndrome; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised; PTSD, post-traumatic stress disorder.
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INTRODUCTION |
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The symptoms most commonly reported by Gulf veterans include fatigue, muscle/joint pain, headache, difficulty concentrating, memory loss, sleep disturbance, and skin rash (13). Some veterans fulfill the clinical case criteria for illness resembling chronic fatigue syndrome (CFS), an interpretation that has been confirmed in several studies (15, 16). One epidemiologic study of Gulf veterans seeking health care found that 16.8 percent of veterans reported symptoms consistent with CFS (17), while another small population-based study found an estimated minimum prevalence of 2.2 percent (18). All of these rates are significantly higher than the rate seen in nonveterans (19).
The fact that the prevalence of CFS is so much higher among veterans deployed to the Persian Gulf suggests two possible etiologic factors: 1) some environmental factor specific to the Gulf region and 2) the stress of deployment and combat. The availability of data on the Gulf War veteran population has allowed us to evaluate the role of stress in the development of CFS.
One commonly acknowledged indicator of life-threatening stress is the presence of post-traumatic stress disorder (PTSD). In an evaluation of 76 health-care-seeking Gulf veterans who fulfilled the published case definition for CFS (15) or its less severe variant, idiopathic chronic fatigue, 50 percent were also found to have PTSD (20). Moreover, a population study of Gulf veterans indicated that those with PTSD had significantly more somatic complaints than those without PTSD (21).
In 1995, the Department of Veterans Affairs initiated a health survey entitled "National Health Survey of Gulf War Era Veterans and Their Families," designed to compare the health of a population-based, stratified random sample of 15,000 US troops deployed into the Gulf region with that of 15,000 troops deployed elsewhere (22). We aimed to estimate and compare the prevalence of two symptom-based medical conditions, PTSD and CFS, in these two groups of veterans. Furthermore, we evaluated the etiologic role of deployment-related stress on the development of these conditions.
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MATERIALS AND METHODS |
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A stratified random sampling method was adopted to ensure that each subgroup was adequately represented among the 15,000 Gulf veterans and 15,000 non-Gulf veterans. The entire population of troops deployed to the Gulf area was stratified by gender (male and female), unit component (active, reserve, and National Guard), and branch of service (Army, Navy, Air Force, and Marine Corps). Women and those who served in reserve or National Guard units were oversampled so that one fifth of the sample would be female (n = 3,000), one fourth would be National Guard members (n = 4,000), and one third would be reservists (n = 5,000). The proportions of these subgroups in the entire population of deployed troops were 7 percent, 7 percent, and 10 percent, respectively. Similarly, the population of 800,680 nondeployed troops was stratified by gender, unit component, and branch of service, and from each stratum a requisite number of troops was randomly sampled to mirror the number in the same stratum in the Gulf-deployed troops. Table 1 gives the final distribution of Gulf and non-Gulf veterans according to the selection criteria.
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In phase II, telephone calls were made to the remaining nonrespondents; computer-assisted telephone interviewing software was used to obtain responses to the questionnaire mailed in phase I. During phase II, a random sample of 4,200 respondents from phases I and II was selected and asked to provide written authorization to allow retrieval of their medical records; we used those records to substantiate information on selected self-reported health conditions obtained from the respondents.
Questionnaire instruments
A self-administered questionnaire was used to obtain information from study subjects concerning exposure to possible risk factors, potentially confounding variables, presence of various symptoms, measures of functional impairment and limitation of activity, and medical history. To increase the anticipated low response rates typically associated with postal questionnaires, we kept the instrument relatively short; questions were simple and straightforward. We asked a minimum number of questions on demographic and military variables to avoid making the questionnaire any longer than necessary. Basic data on demographic and military variables were available from Defense Manpower Data Center and Veterans Affairs records.
A self-report symptom inventory comprising 48 items representative of the symptoms commonly reported by outpatients was used to assess the prevalence of somatic and psychological symptoms (23). The symptom checklist collected information on the time of onset and severity of symptoms; eight symptoms for diagnosing CFS/idiopathic chronic fatigue were included (15). Questionnaire items from the National Health Interview Survey were selected to evaluate limitation of activity, prevalence of chronic conditions, self-assessed health status, and use of medical services, including physician contacts and hospitalization (24).
We used the PTSD Checklist, a brief screening instrument for PTSD, to estimate current prevalence of PTSD (25). The PTSD Checklist consists of 17 items that correspond to the PTSD symptoms given in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R). We considered persons with scores of 50 or higher on the PTSD Checklist to have met the criteria for PTSD. A cutoff of 50 points on the PTSD Checklist was a good predictor of PTSD diagnosis based on the Structured Clinical Interview for DSM-III-R among Vietnam veterans (sensitivity = 0.82; specificity = 0.83) (26).
For assessment of CFS, we adopted the 1994 Centers for Disease Control and Prevention revised case definition (15). The diagnosis of CFS is made only after excluding alternative medical causes of chronic fatiguing illness. Therefore, we excluded veterans with the following self-reported clinical conditions from the list of veterans who otherwise met the criteria: arthritis, diseases of the tendons, skin cancer, any other cancer, cirrhosis of the liver, hepatitis, any other liver diseases, colitis, diabetes, any other endocrine disorders, repeated seizures, neuralgia or neuritis, any disease of the genital organs, coronary heart diseases, stroke or cerebral vascular accident, tachycardia, asthma, other lung diseases, and frequent bladder infections. To be considered to have CFS, a veteran also had to report having at least four of the following symptoms: sore throat, tender lymph nodes, headache, arthralgia, myalgia, unrefreshing sleep, and substantial problems with cognitive function, and to report that even minimal effort exacerbated the entire symptom complex. The Centers for Disease Control and Prevention case definition distinguishes "prolonged fatigue" (fatigue lasting 1 month or longer) from "chronic fatigue" (persistent or recurring fatigue during 6 or more consecutive months of illness). On the questionnaire instrument, we queried about whether the fatigue had been present during the past year and, if so, whether it had been present during the past month. This is a modification of the published 1994 clinical case definition that we made to assure the presence of current symptoms at the time of the survey. Since respondents were not directly evaluated by a clinician, our diagnosis of CFS should be considered to represent CFS-like illness.
Stressor severity
We derived an ordinal variable for stressor severity. We defined nondeployed veterans who had been members of a reserve or National Guard unit as veterans with minimal stress. We defined reservists or National Guard members who had been deployed to a location other than the Gulf as veterans with moderate stress. We defined reservists or National Guard members who had been deployed to the Persian Gulf as veterans with high stress. We further stratified the high-stress group on the basis of combat exposure. To do this, we identified those Gulf veterans who 1) reported being "involved in direct combat duty," 2) had "witnessed any deaths," or 3) "wore chemical protective gear (other than for training) or heard chemical alarms sounding." In the analyses, we produced groups with monotonically increasing exposure to stress according to the number(s) of these exposures experiencedthat is, no exposure or one, two, or three exposures (high-combat0, high-combat1, high-combat2, and high-combat3).
Statistical analysis
This was a probability sample in which the population of 693,826 Gulf veterans was stratified by unit, gender, and branch and a probability sample was selected from each stratum. The selection probabilities varied across strata because of oversampling of women, reservists, and National Guard members. Such a design complicated the statistical analysis, since the observations were not independent and identically distributed. Failure to account for the design in the statistical analysis would have resulted in underestimation of standard errors. Consideration of the survey sampling plan and design variables (stratum and weighting variables) permitted inference to the population.
The survey objective was to estimate the prevalence of certain disease entities for the population. The prevalences of PTSD and CFS-like illness for the entire Gulf War veteran population (N1 = 693,826) and the nondeployed population (N2 = 800,860) were obtained from weighted estimates of individual military strata values. To estimate the confidence intervals of the prevalence rates and odds ratios, we used SUDAAN software, which provides consistent variance estimators for statistics derived from complex sample designs (27). Other analyses included contingency table analysis to examine differences with respect to demographic and military factors for the Gulf veterans and the non-Gulf veterans (28). We used the stratified analysis of Cochran-Mantel-Haenszel (29) to compute odds ratios and 95 percent confidence intervals for the relation between Gulf service status and PTSD, with adjustment for gender, age in 1991 (<30 years vs. 30 years), marital status (single vs. ever married), rank (enlisted vs. officer or warrant), and unit component (active duty, National Guard, or reserve). Similarly, we computed adjusted odds ratios and 95 percent confidence intervals for Gulf service status and CFS-like illness, adjusted for age, marital status, rank, and unit component. Computations were carried out using standard SAS software (28).
We developed a 6 x 2 table where the row variable, deployment-related stress, was ordinally scaled at six levels, ranging from minimal stress (not activated) to highest stress (deployed to the Gulf with three possible types of combat exposure); the column or response variable, CFS-like illness (or PTSD), was dichotomous and can be considered ordinal. The strategy for assessing association when both row and column variables are ordinal involves assigning scores to the levels of both variables and evaluating their correlation. We adopted two correlation statistics. First, the Cochran-Armitage trend test looks for trends in binomial proportions across the levels of an ordinal covariate (30, 31). Second, the Mantel-Haenszel correlation statistic is developed by assigning scores to the columns and rows of the table and measuring the association between stress and CFS-like illness (or PTSD). We specified modified ridit scores (29). Further details on statistical methods are given in the Appendix.
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RESULTS |
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We attempted to assess whether characteristics of respondents were significantly different from those of nonrespondents with respect to self-perceived exposure in the Gulf theater or postwar health status. During phase I, 30,000 questionnaires were mailed initially, and two separate follow-up recruitment packets were sent to nonrespondents. The phase II telephone survey was targeted for nonrespondents after completion of the phase I survey. Therefore, each successive group of respondents could be considered a group of nonrespondents in comparison with the preceding group of veterans, because they would have remained nonrespondents without the follow-up recruitment efforts. We kept a record of the date on which each survey questionnaire was received and classified each respondent as completing his/her survey form during phase I, wave 1, 2, or 3, or phase II.
For three selected exposures during the Gulf War1) contact with prisoners of war, 2) exposure to nerve gas, and 3) other exposures considered harmfulthere were no significant differences in the proportions of individuals reporting positively for each of three exposure questions by survey respondent group (phase I, wave 1, 2, or 3, and phase II). Likewise, in both the Gulf and non-Gulf veteran groups, five categories of self-reported general health status (i.e., excellent, very good, good, fair, and poor) did not differ significantly among the four survey respondent groups. In other words, veterans who chose to participate in the survey earlier did not perceive themselves to be more or less healthy than others. It did not appear that self-perceived exposure to harmful situations in the Gulf theater or current health status contributed substantially to their decision as to whether or not to participate.
Characteristics of veterans with PTSD or CFS and prevalence of conditions
The percentage distributions of selected demographic and military characteristics among the Gulf and non-Gulf veterans who participated in the survey are presented in table 2. The subgroups of Gulf veterans who met the criteria for PTSD or CFS-like illness were compared with the total number of Gulf veteran respondents to determine whether these conditions were concentrated in particular demographic or military strata. There were some differences in demographic and military characteristics when those who met the PTSD criteria were compared with all Gulf veterans. The veterans positive for PTSD criteria (n = 1,381) were more likely to be female, older, non-White, in the enlisted ranks, and in the Army and National Guard (p < 0.001 for each characteristic). The veterans positive for CFS-like illness (n = 640) were more likely to be younger (p < 0.001), single (p < 0.001), in the enlisted ranks (p < 0.001), in the Army or Marines (p < 0.001), and in the reserves (p < 0.02).
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DISCUSSION |
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Earlier research has shown that rates of PTSD are sensitive to stressor intensity (32). However, to our knowledge, no prior study has examined the entire breadth of stressor intensity as was done here. The data reported here make it clear that rates of PTSD track stressor intensity extremely closely. Rates of PTSD increased monotonically across these six stressor intensities, from 3.3 percent in the least stressful situation to 22.6 percent in the most stressful situation. This result is impressive when we realize that the period of stressor exposure during this war, relative to other conflicts, was relatively short. The significant relation between stressor intensity and PTSD leads to two conclusions: 1) that the existing case definition for PTSD adequately captures a stress-related behavioral syndrome and 2) that rates could be substantially higher in conflicts where stressor intensity and/or duration were greater than in the Gulf War.
Rates of CFS-like illness did show a relation to stressor intensity, but the pattern was quite different from that for PTSD. The rate of CFS-like illness was 0.8 percent for the nondeployed, while the rate for veterans deployed elsewhere but not in the Gulf was 1.7 percent. Rates again increased to 5.4 percent for veterans deployed to the Gulf but in noncombat roles. Rates of CFS-like illness did not change significantly for Gulf veterans in the more stressful situations related to combat. It appears that deployment-related stress has a role in the genesis of CFS in a veteran population. However, the data do not rule out the possibility that, in addition to stress, some unmeasured factors specific to serving in the Gulf could be responsible for the high rates of CFS among Gulf War veterans.
This overall pattern indicates some parallels between CFS-like illness and PTSD in that both have a relation to stress. However, the pattern of that relationlinear for PTSD and linear for CFS only at lower stressor intensitiessuggests that the two conditions are not merely variants of one another. Except for the data presented here, which were collected from a Gulf-War-era veteran population, no study has clearly shown an existing relation between stress and CFS in civilians. An initial small case-control study did find that CFS patients reported a higher rate of exposure to serious stressors in the year prior to their illness onset (33). Since that study did not randomly recruit control subjects and did not use rigid inclusion and exclusion criteria to identify CFS patients, a follow-up study was conducted in which both of those deficiencies were corrected. That study found no difference in self-reported exposure to stressors between CFS patients and controls (J. G. Dobbins and B. H. Natelson, Veterans Affairs Medical Center (East Orange, New Jersey), personal communication, 2002). Obviously, such studies have the limitation of a small sample size. Although veterans with CFS are demographically very different from nonveteran CFS patients (nonveteran patients are predominantly White females), one might expect to find, with larger sample sizes, that exposure to psychological stress can be a risk factor for developing CFS among nonveterans also.
The reason why CFS is related to only lower intensities of stressor exposure is unclear. In experimental work, we have shown that stressor intensity is an important variable in predicting the medical consequences of stress (34). One possibility might be that stress, although a factor for CFS, plays a relatively minor role compared with other contributing factors unique to the Gulf War environment.
This survey is one of a few population-based studies of Gulf veterans with contemporary veteran controls. The relatively high participation rate of 70 percent and lack of evidence of response bias, either by self-reported general health status or in theater exposure status, indicate that there is little likelihood of selection bias in this self-administered postal survey questionnaire. In this population-based study, 10.1 percent of the entire deployed population of 693,826 Gulf War troops was estimated to have PTSD during the month prior to completing the questionnaire. This prevalence is compared with 4.2 percent of the 800,680 comparable veterans who were not deployed to the Gulf region. An estimated 4.9 percent of Gulf veterans and 1.2 percent of non-Gulf troops met the modified case definition for CFS. The results suggest that PTSD and CFS may account for a substantial portion of Gulf veterans who complain of a medically unexplained constellation of symptoms.
The Department of Defense should include screening for PTSD/CFS as part of postdeployment clinical examinations for troops returning from future military conflicts, and appropriate follow-up health care should be planned by both the Department of Defense and the Department of Veterans Affairs.
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ACKNOWLEDGMENTS |
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APPENDIX |
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NOTES |
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REFERENCES |
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