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Relationship of Physical Symptoms to Posttraumatic Stress Disorder Among Veterans Seeking Care for Gulf War-Related Health Concerns

From the Deployment Health Clinical Center (C.C.E., X.L., B.D.M., R.F.M.), Walter Reed Army Medical Center, Washington, DC; and the Department of Psychiatry (C.C.E., X.L., R.U.), Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Address reprint requests to: Dr. Engel, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814. Email: cengel{at}pobox.com

	ABSTRACT

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OBJECTIVES: Studies of the relationship of posttraumatic stress disorder (PTSD) to physical symptoms in war veterans consistently show a positive relationship. However, traumatic experiences causing PTSD may correlate with other war exposures and medical illnesses potentially accounting for those symptoms.

METHODS: We analyzed data obtained from 21,244 Gulf War veterans seeking care for war-related health concerns to assess the relationship of PTSD to physical symptoms independent of environmental exposure reports and medical illness. At assessment, veterans provided demographic information and checklists of 15 common physical symptoms and 20 wartime environmental exposures. Up to seven ICD-9 provider diagnoses were ranked in order of estimated clinical significance. The relationship of provider-diagnosed PTSD to various physical symptoms and to the total symptom count was then determined in bivariate and multivariate analyses.

RESULTS: Veterans diagnosed with PTSD endorsed an average of 6.7 (SD = 3.9) physical symptoms, those with a non-PTSD psychological condition endorsed 5.3 (3.5), those with medical illness endorsed 4.3 (3.4), and a group diagnosed as "healthy" endorsed 1.2 (2.2). For every symptom, the proportion of veterans reporting the symptom was highest in those with PTSD, second highest in those with any psychological condition, third highest in those with any medical illness, and lowest in those labeled as healthy. The PTSD–symptom count relationship was independent of demographic characteristics, veteran-reported environmental exposures, and comorbid medical conditions, even when symptoms overlapping with those of PTSD were excluded.

CONCLUSIONS: PTSD diminishes the general health perceptions of care-seeking Gulf War veterans. Clinicians should carefully consider PTSD when evaluating Gulf War veterans with vague, multiple, or medically unexplained physical symptoms.

Key Words: unexplained physical symptoms • posttraumatic stress disorder, • Gulf War veterans • Comprehensive Clinical Evaluation Program • multivariate analysis, • war-related illnesses.

Abbreviations: CCEP = Comprehensive Clinical Evaluation Program; ICD-9 = International Classification of Diseases, ninth revision; PTSD = posttraumatic stress disorder.

	INTRODUCTION

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Epidemiological studies have consistently found that persons with PTSD describe more physical symptoms than those without PTSD. Studies of Vietnam veterans (1, 2); Israeli combat veterans (3, 4); communities (5); urban young adults (6); women with histories of sexual assault, criminal victimization, and Vietnam combat (7–9); gastroenterology clinic attendees (10); disaster victims (11–14); and firefighters (15) have suggested links between trauma or PTSD and various physical health complaints. Davidson et al. (5) examined a community-based sample of North Carolina adults and found that PTSD was associated with a 90-fold increase in the likelihood of somatization disorder. Of the 39 individuals with a history of PTSD, 5 (11.7%) were diagnosed with somatization disorder, whereas only 4 of the 2946 (0.1%) without a history of PTSD had this disorder (5). Other studies have noted somatization disorder in 8 to 15% of veterans with PTSD receiving mental health care (16–19).

The putative relationship of physical symptoms to PTSD has important clinical implications for veterans with persistent or undiagnosed physical symptoms since serving in the Gulf War. Baker et al. (20) found that physical symptoms were strongly related to a diagnosis of PTSD among a group of 188 Gulf War veterans. The 13% of veterans with PTSD were between 4.8 and 16 times more likely to report different physical symptoms. Although the magnitude of these associations is impressive, neither this study of Gulf War veterans nor others studying the relationship of physical symptoms to PTSD have controlled for the possible confounding effect of medical illness and the wide range of environmental exposures that may have caused them. Wolfe et al. (21) examined Gulf War veterans and found that PTSD had a statistically significant but small relationship with increased health symptom reporting. However, almost two-thirds Gulf War veterans with elevations in physical symptoms had no axis I psychiatric diagnosis, suggesting that other explanations for physical symptoms were operative (21).

War veterans with the greatest exposure to traumatic experiences may also be the ones most affected by toxic exposures and related medical illness. For example, Helzer et al. (22) found that among Vietnam veterans wounded in action, about 20% had PTSD, compared with 1% of those who were not wounded. During the Gulf War, troops faced a range of potential toxic exposures, including smoke from burned excrement, burning oil wells, and diesel exhaust; toxic paints and pesticides; sand and other particulates; depleted uranium; infectious agents; chemoprophylactic agents; immunizations; and perhaps even chemical or biological warfare agents (23, 24). Increased toxic exposures and related medical illnesses among those with PTSD may therefore mediate the previously observed relationship between PTSD and physical symptoms. Proctor et al. (25) compared Gulf War veterans with individuals deployed to Germany and found that Gulf veterans reported significantly greater physical health symptoms even after controlling for PTSD.

We wanted to test the relationship of PTSD to physical symptoms after controlling for possible confounding effects of exposures and medical illness. Several questions were of concern to us: 1) Does PTSD have a direct and positive effect on a Gulf veteran’s physical symptoms? 2) Is the impact of PTSD on physical symptoms mediated or confounded by coexisting medical illness or toxic war exposures? 3) Is the impact of PTSD on physical symptoms consistent even for symptoms of no apparent neuropsychiatric basis? 4) To what extent might PTSD explain the unexplained illnesses veterans have experienced since their service in the Gulf?

To address these questions we analyzed data from the CCEP, a worldwide US Department of Defense program established to evaluate the health of Gulf War veterans with war-related health concerns. The data generated from CCEP are not representative of all Gulf War veterans but are nonetheless useful for hypothesis screening (26) and can help us to understand the health concerns of care-seeking veterans (27).

	METHODS

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Comprehensive Clinical Evaluation Program
Because the purpose of the CCEP is primarily clinical, participants seek CCEP assistance on the basis of self-assessed need and thus are not recruited by use of a systematic sampling strategy. Written guidelines help program clinicians decide how to evaluate participants and when to refer them to specialists. The approach to specialty consultations, testing, and clinical assessment is lengthy, inclusive, and thorough. At the time of presentation, the CCEP is fully explained to participants and written consent is obtained to use their data for aggregate examination of illnesses after Gulf War service. Current analyses focus on the first 21,244 Gulf War veterans who completed the CCEP.

Measures
All CCEP participants answered a series of questions about demographics, symptoms, and Gulf War–related environmental exposures. Physical symptoms were determined using a 16-item symptom checklist. Checklist symptoms included abdominal pain, bleeding gums, depressed mood, diarrhea, difficulty concentrating, fatigue, hair loss, headache, joint pain, memory loss, muscle pain, rash, shortness of breath, sleep disturbance, weight change, and "other symptoms." Analyses consider each symptom (reportedly present/not present) as well as the total symptom count (number of symptoms reported of 16). A second symptom count was also considered that excluded five symptoms potentially overlapping with those of PTSD and other mental disorders (depressed mood, difficulty concentrating, memory loss, sleep disturbance, and fatigue).

On completion of the CCEP clinical evaluation, the provider coordinating evaluations at the medical facility where the evaluation is performed transcribes the diagnoses as ICD-9 codes and rank-orders them according to their estimated clinical importance. Provider diagnoses used in these analyses were ICD-9 psychological conditions (codes 290–320), PTSD (code 309.81), medical conditions (codes 0–289.99 and 320.01–999.99), and "healthy" (code V65.5).

Provider diagnoses were recorded dichotomously (diagnosed/not diagnosed). An environmental exposure count was created using the number of exposures endorsed by the veteran (number reported of 20). Exposures were determined with a checklist like the one used for symptoms. Exposures addressed were oil fire smoke, tent heater smoke, chemical agent–resistant paint, other paints, solvents, diesel fuel, other petrochemicals, depleted uranium, nerve gas, mustard gas, microwaves, pyridostigmine bromide pills, insect repellents/flea collars, botulism immunization, anthrax immunization, malaria prophylaxis, food not provided by the military, contaminated food, water not provided by the military, and contaminated water. Each exposure was measured dichotomously (experienced/not experienced).

Four demographic characteristics were used in multivariate analyses: age (in years at the time of evaluation), gender, marital status (two dichotomous variables: currently married/other and currently not married/other), and ethnicity (white/nonwhite). Cigarette smoking (two dichotomous variables: nonsmoker/other and current or past smoker/other) is considered in analyses as a non–Gulf War–related health risk factor. The two coding strategies used for marital status and cigarette smoking lessened the cumulative loss of subjects due to missing values in multivariate analyses. As a result, there are only 12 missing cases in the data analysis.

Statistical Analysis
Bivariate analyses examined the relationship of symptoms to PTSD and psychological conditions besides PTSD. A correlation matrix of all variables used in the analysis was examined (available on request). We used multiple regression to model the symptom counts while adjusting for potentially confounding variables (war-related environmental exposures, medical illness, psychological conditions besides PTSD, and demographic characteristics, including smoking status). A stepdown analytic approach was used to test the putative relationship of PTSD to physical symptoms and then explore whether exposures or medical illness confounded the direct effect of PTSD on physical symptoms. First, a full model including all independent variables was specified, and then medical illness and exposure count were removed sequentially from the model. As these variables were removed, we examined for appreciable changes in the regression coefficient for the PTSD variable. If the magnitude of such changes are small (<10%), then it is reasonable to conclude that the direct impact of PTSD on Gulf veterans’ physical symptoms is not significantly confounded by war-related environmental exposures and current medical status.

	RESULTS

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Table 1 presents the distribution of symptom counts among 21,232 CCEP participants (the effective sample excluding the 12 missing cases). A total of 16.2% of veterans did not report any symptoms, whereas 8.6% reported 10 or more. A majority of veterans reported fewer than four symptoms.

In Table 3 the relationship of PTSD to checklist symptoms was examined using 4 overlapping diagnostic groupings: those with a PTSD diagnosis, those with any diagnosed psychological condition (including PTSD), those with any diagnosed medical condition (including those with a coexisting psychological condition), and those diagnosed as healthy. Among those diagnosed with a medical condition, the proportion having each of the checklist symptoms is significantly lower than for the group diagnosed with PTSD or the group diagnosed with any psychological condition. Veterans diagnosed as healthy were the least likely to report various physical symptoms. For each symptom, the proportion of healthy veterans with that symptom is much lower than those diagnosed with medical or psychological conditions. However, symptoms were not infrequent even among those veterans diagnosed as healthy. Here again, symptom counts revealed the same ordering effect even after exclusion of neuropsychiatric symptoms (PTSD: 3.7, SD = 2.6; psychological conditions: 3.2, SD = 2.3; medical conditions: 2.5, SD = 2.1; healthy: 0.9, SD = 1.4; not shown in Table 3).

When we modeled the symptom count that excluded symptoms overlapping with those of PTSD in exactly the same manner, we found very similar results. For example, in model A, the regression coefficient for PTSD was 1.92 (SE = 0.068); for psychological conditions but not PTSD it was 1.29 (0.033); for medical conditions it was 0.55 (0.034); and for war-related environmental exposures it was 0.080 (0.004). The PTSD coefficient was similarly stable across models (10% difference from model C to model A), and model A accounted for only 11.5% of the variance in symptom count.

	DISCUSSION

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The results shown above provide evidence that care-seeking Gulf War veterans diagnosed with PTSD report significantly more physical symptoms than care-seeking Gulf War veterans who were not diagnosed as having PTSD. The relationship between PTSD and different physical symptoms is remarkably consistent, irrespective of whether a given symptom overlaps with the diagnostic criteria for PTSD. Furthermore, the positive association between physical symptom count and a diagnosis of PTSD remains nearly unchanged even after taking into account the potentially confounding influences of veteran-reported environmental exposures and provider-diagnosed medical illness. These war-related environmental exposures and medical illnesses were, however, important determinants of physical symptoms in their own right.

Veterans diagnosed with PTSD reported the highest symptom counts, even after adjusting for all important and potentially confounding variables available to us, including the presence of medical conditions and war-related environmental exposures. This effect persisted even when common symptoms that overlap with the diagnostic criteria for many mental disorders, such as depression, difficulty concentrating, sleep changes, and fatigue, are removed from the physical symptom count. Psychological conditions besides PTSD were also related to increased physical symptom counts, although less so than was PTSD. Indeed, PTSD was associated with the highest proportion of symptom reporters for each of the 16 checklist symptoms examined, followed by other psychological conditions and then medical conditions and individuals described as healthy by the examining physician. This ordering of effect was preserved even for symptoms that have little or no apparent relationship to either the phenomenology or neurophysiology of PTSD, such as bleeding gums.

There are several limitations that must be considered when attempting to ascertain the validity and generalizability of our findings. The absence of symptom severity measurements is a drawback. It is not clear whether the symptoms that veterans endorsed are clinically significant. However, it is reasonable to assume that the number of symptoms endorsed is a surrogate measure of overall symptom severity. Veterans participating in CCEP are a selected sample assessed within a unique context, and the degree to which these findings may be extended to all Gulf War veterans is unknown. For instance, compensation is often at stake during CCEP evaluations, and this may distort veterans’ symptom reports. Therefore, it may not be appropriate to generalize these findings to all Gulf War veterans. Interpretation of these data is also complicated by the fact that PTSD and psychological condition diagnoses were not uniformly made in specialty mental health care settings, and the validity of diagnoses is not well characterized. The validity of CCEP PTSD diagnoses, however, was supported in previous analyses showing that veteran-reported Gulf War stressors were significantly related to the CCEP diagnosis of PTSD but not to other CCEP psychological conditions (28, 29). Furthermore, the multicenter, clinical, and worldwide nature of CCEP means that the average CCEP assessment is likely to more approximate providers’ routine diagnostic practices than an epidemiological study using research diagnostic practices. Random regional variations in diagnostic practices can offset one another in a large worldwide clinical sample such as the one that CCEP offers. Lastly, the cross-sectional nature of the sample weakens the confidence with which causal inferences may be made. For example, because symptoms and distress were assessed simultaneously, one cannot discern whether distress may be causing amplified estimates of physical symptom severity or whether physical symptoms are resulting in distress.

The multivariate models we presented represent a conservative test of the hypothesis that PTSD is linked to physical symptoms among Gulf War veterans. Our backward stepwise approach to modeling the PTSD–physical symptom link assumes that the impact of PTSD on physical symptoms is not mediated by smoking or medical illness. Research on veterans from other wars suggests that PTSD may well antedate and subsequently alter their health habits and illness experience (4). These effects, although possibly occurring among CCEP participants, seem minor and would cause us to err on the side of a falsely negative or underestimated PTSD–physical symptom link. Similarly, the effect previously mentioned of random misclassification of PTSD due to regional variation in diagnostic practices would increase the chance of falsely accepting the null hypothesis. These considerations suggest that the relationship of PTSD to physical symptoms may indeed be even stronger than we have estimated.

Assuming Gulf War veterans with PTSD are more likely to use medical services than are other Gulf War veterans, one would expect the prevalence of PTSD among CCEP participants to be higher than it is in the general Gulf War veteran population. Only 5.2% of CCEP participants were diagnosed with PTSD. Although a great deal of empirical research consistently implicates PTSD as an important cause of physical symptoms, it seems clear that there are other important and potentially Gulf War–related causes of physical symptoms among ill Gulf War veterans. Some illness may be due to other psychological conditions (many of them underrecognized and readily treatable in primary care settings). Other illness may well relate to physical etiologies or important environmental exposures experienced in the Gulf. Longitudinal studies are under way to address the long-term impact of PTSD on Gulf War veterans’ health (21, 25) (Table 4).

	NOTES

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The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of Defense, or the US Government.

Received for publication January 4, 2000.

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