The relationship between Gulf War illness, brain N-acetylaspartate, and post-traumatic stress disorder

A previous study (Haley RW, Marshall WW, McDonald GG, Daugherty MA, Petty F, Fleckenstein JL: Brain abnormalities in Gulf War syndrome: evaluation with 1H MR spectroscopy. Radiology 2000; 215: 807-817) suggested that individuals with Gulf War Illness (GWI) had reduced quantities of the neuronal marker N-acetylaspartate (NAA) in the basal ganglia and pons. This study aimed to determine whether NAA is reduced in these regions and to investigate correlations with other possible causes of GWI, such as psychological response to stress in a large cohort of Gulf War veterans. Individuals underwent tests to determine their physical and psychological health and to identify veterans with (n=81) and without (n=97) GWI. When concentrations of NAA and ratios of NAA to creatine- and choline-containing metabolites were measured in the basal ganglia and pons, no significant differences were found between veterans with or without GWI, suggesting that GWI is not associated with reduced NAA in these regions. Veterans with GWI had significantly higher rates of post-traumatic stress disorder, supporting the idea that GWI symptoms are stress related.     

Credibility of neuropsychological performances of Persian Gulf War veterans and military control subjects participating in clinical epidemiological research

We investigated whether Persian Gulf War veterans (GWVs) were more likely than Persian Gulf War-era veterans deployed elsewhere (GEVs) to have noncredible neuropsychological examinations. A total of 301 GWVs and 99 GEVs underwent neuropsychological testing. The credibility of 173 examinations showing impairment was evaluated based on test performances, clinical background, psychometric measures, and other self-report data. All 11 examinations judged less than fully credible by one neuropsychologist, plus 19 examinations judged impaired but credible, were then evaluated independently by two more neuropsychologists. Noncredibility was judged with excellent reliability (93% agreement). Seven examinations were judged noncredible. Rates of noncredibility did not differ between GWVs (1%) and GEVs (4%). The pattern of associations of noncredible examinations with cognitive, psychological, and clinical variables generally indicated defective neuropsychological scores, with no coherent pattern, and personality disorder. Findings supported the validity of noncredibility judgments and suggested that noncredible examinations are not a significant problem in neuropsychological investigations of GWVs.     

Predicting costs of Veterans Affairs health care in Gulf War veterans with medically unexplained physical symptoms

Measures of post-traumatic stress disorder (PTSD) and depression were used to predict Veterans Affairs outpatient treatment costs among Persian Gulf War veterans with medically unexplained physical symptoms. Patients (N = 206) enrolled in a Veterans Affairs primary care clinic for Persian Gulf War veterans completed study assessments at the initial appointment or at a proximal follow-up visit. Costs of care for mental health, medical, and pharmacy services for these veterans were computed for the subsequent 6-month period. Depression and PTSD symptoms explained a significant share of variance in costs of mental health care and pharmacy services, after adjustment for covariates. None of the mental status measures was significantly related to costs of medical care. Models using global measures of mental health status were as robust as models using disorder-specific measures of PTSD and depression in predicting mental health care and pharmacy costs. The implications of these findings for anticipating costs of care for Persian Gulf War veterans are discussed.     

Pyridostigmine bromide intake during the Persian Gulf War is not associated with postwar handgrip strength

Many Persian Gulf War veterans took pyridostigmine bromide (PB) during the Persian Gulf War. Previous research suggests that PB intake and insecticide exposure may reduce muscular strength. During 1994 and 1995, we examined the relationships between self-reported PB intake, self-reported exposures, and handgrip strength among 527 Gulf War veterans (GWVs) and 969 nondeployed veterans of that era (NDVs). We found that 25.4% and 6.7% of the GWVs and NDVs, respectively, reported generalized musucle weakness (for 1 month or longer) since the Gulf War (July 1990). Many veterans also reported exposure to insecticide during the war. Dominant handgrip strength was measured three times with a hand-held dynamometer in subjects standing with the elbow bent at a right angle. Multiple linear regression revealed that handgrip strength was negatively associated with age (p = 0.001) and female gender (p < 0.001). Handgrip strength was also found to be positively associated with height (p < 0.001), but it was not associated with PB intake (p = 0.558). Exposure to insecticides had no major effect on handgrip strength. These data suggest no association between PB intake and postwar handgrip strength.     

Clinical findings of the second 1000 UK Gulf War veterans who attended the Ministry of Defence's Medical Assessment Programme

OBJECTIVE: To review the diagnoses made in the second 1000 veterans of the Gulf conflict 1990-91 seen in the Ministry of Defence's Gulf Veterans' Medical Assessment Programme and to determine the main conditions related to Gulf service. DESIGN: Case series of 1000 consecutive Gulf veterans who presented to the programme between 25 February 1997 and 19 February 1998. SUBJECTS: Gulf War veterans. MAIN OUTCOME MEASURES: Assessment of the patient's health status. Diagnosis of medical and psychiatric conditions using ICD-10. RESULTS: 204 patients were unwell. 309 patients had organic disease, of whom 248 were well, 252 had psychiatric conditions which remained active in 173. The remaining 79, now well, had had psychiatric disorders following Gulf service. The principal psychiatric diagnosis was post traumatic stress disorder and the majority arose as a result of Gulf service. CONCLUSION: 796 (80%) veterans were well. There were 309 (31%) patients with organic disease. 252 (25%) veterans had psychiatric conditions of which 173 (69%) had an active diagnosed disorder and post traumatic stress disorder was the predominant condition. The pattern of disease is similar to that seen in NHS practice. We found, like others, no evidence to support a unique Gulf War syndrome. Post conflict illnesses have many common features.     

A histopathological study of head and neck specimens from a cohort of Persian Gulf War military veterans

Approximately 700,000 U.S. military personnel were deployed to the Persian Gulf region during the Gulf War. Since their return, many Persian Gulf War veterans (GWVs) have presented with various medical symptoms, including those related to the head and neck. A study devoted to the histopathology of head and neck specimens from GWVs has not been previously reported. Surgical, autopsy, and cytological specimens from GWVs were evaluated by light microscopy at the Armed Forces Institute of Pathology with additional studies as required and were entered into the Kuwait Registry. The Kuwait Registry contained 361 head and neck specimens from 264 GWVs. Neoplasms were relatively infrequent, including six malignant neoplasms and 14 benign neoplasms. The most frequent diagnoses were chronic sinusitis, allergic rhinitis, and lymphoid hyperplasia of the tonsils. These conditions are frequently encountered in routine anatomic pathology practice in the general U.S. population.     

The Department of Defense's Persian Gulf War registry year 2000: an examination of veterans' health status

This study examined the health status of 46,633 Persian Gulf War theater veterans who received full clinical evaluations in the Department of Defense's Gulf War Comprehensive Clinical Evaluation Program (CCEP) as of spring 2000. Clinical data analyzed included demographic information, 15 health symptoms, 19 wartime exposures, and primary and secondary physician-determined medical diagnoses based on International Classification of Diseases, 9th Revision, Clinical Modification, criteria. Findings and discussions are arrayed, by gender, with comparative 1996 data from the Department of Veterans Affairs Health Examination Registry Program. Many veterans reported fewer physical symptoms now than during the time of the Gulf War. Many endorsed symptoms of joint pain, fatigue, weight change, and sleep disturbances. Most reported exposure to diesel fuel and the nerve agent antidote pyridostigmine bromide; far fewer female veterans reported combat involvement. The most frequent primary or secondary diagnosed medical conditions were musculoskeletal/connective tissue diseases, ill-defined conditions, and mental disorders. Female veterans were diagnosed more frequently with mental disorders. Symptom endorsement and diagnosis rates between the CCEP and the Department of Veterans Affairs registry were not dissimilar. Overall, the self-reported general health of veterans with symptoms was much poorer (females had higher rates of "fair to poor" health than males) than that of veterans with no reported symptoms.     

Incarceration and veterans of the first Gulf War

OBJECTIVE: This study investigated the prevalence of incarceration and the association with deployment among veterans of the first Persian Gulf War (GW). METHODS: A structured telephone interview of military personnel from Iowa deployed to the Persian Gulf and a comparison sample of nondeployed military personnel was conducted. The interview consisted of validated questions, validated instruments, and investigator-derived questions to assess relevant medical and psychiatric conditions. A total of 4,886 subjects were randomly drawn from one of four study domains, i.e., GW regular military, GW National Guard/Reserve, non-GW regular military, or non-GW National Guard/Reserve. Symptoms of medical conditions, psychiatric disorders, and health care utilization were the main outcome measures. RESULTS: Nearly one-quarter (845 of 3,695 subjects, 22.9%) had been incarcerated at some point before the interview ("ever incarcerated"). Ever incarcerated veterans had a higher frequency of psychiatric and medical comorbidity and higher rates of health care utilization. Ever incarcerated status was associated with male gender, enlisted rank, lower educational levels, low levels of military preparedness, discharge from service, cigarette smoking, antisocial traits, court martial and/or other military discipline, having seen a mental health professional, and having used illegal drugs. GW veterans who participated in combat had a modestly higher risk for incarceration after the GW than did noncombatants (odds ratio, 1.6; 95% confidence interval, 1.0-2.5). CONCLUSIONS: Military recruits with a history of incarceration more often displayed problematic behaviors, more often developed psychiatric/medical conditions, and had high rates of health care utilization. A history of incarceration may be a behavioral marker for substance abuse, antisocial behavior, and mental illness. Importantly, GW deployment carried no increased risk of subsequent incarceration overall.     

The war-related illness and injury study centers: a resource for deployment-related health concerns

Combat veterans often return from deployment having experienced a wide range of exposures, symptoms, and medical conditions. The Department of Veterans Affairs established war-related illness and injury study centers to serve combat veterans with unexplained illnesses. We report the exposures, clinical status, and utilization of 53 combat veterans who participated in the National Referral Program (NRP) from January 2002 until March 2004. Participants were primarily male (81%) and served in the Persian Gulf War (79%). Common diagnoses were chronic fatigue syndrome (n = 23, 43%), neurotic depression (n = 21, 40%), and post-traumatic stress disorder (n = 20, 38%). Self-reported exposures related to weaponry, disease prophylaxis, environmental hazards, stress, and poor hygiene. A small increase in mean SF-36V mental component scores (2.8 points, p = 0.009) and use of rehabilitation therapies (1.6 additional visits, p = 0.018) followed the NRP referral. The small gain in mental function suggests that the NRP may benefit combat veterans with long and complex medical histories.     

The health status of Gulf War veterans: lessons learned from the Department of Veterans Affairs Health Registry.

OBJECTIVE: To describe the demographic characteristics and postwar health status of U.S. Gulf War veterans who participated in the Department of Veterans Affairs health examination registry program. DESIGN: Case records of 52,835 veterans who participated in a standardized health examination program were reviewed. SETTING: Participants volunteered for physical examinations at a Department of Veterans Affairs medical treatment facility from August 1992 to September 1996. SUBJECTS: U.S. Gulf War veterans deployed to southwest Asia between August 1990 and 1996. MAIN OUTCOME MEASURE: Demographic, military, symptom, and International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic categories. RESULTS: A wide variety of symptoms and diagnoses were reported without apparent internal variation by military characteristics (branch and service component). The frequency of symptoms (fatigue, skin rash, headache, muscle and joint pain, and memory loss) reported increased over time, whereas the proportion of individuals with physician-diagnosed illnesses remained fairly constant. No single category of disease increased or decreased substantially over time. CONCLUSIONS: Veterans have experienced a wide variety of health problems since their Gulf War service. These problems, in aggregate, are different from what has been seen in other armed conflicts. The Department of Veterans Affairs registry is a very large case series and has failed to identify a single, unique syndrome or new illness after Gulf War service. An epidemiologic study would better define the prevalence of specific symptoms and medical conditions among Gulf War veterans and to what extent any of the conditions identified are associated with Gulf War military service. The knowledge provided by such studies would be important to development of preventive measures and future deployment medical surveillance planning.     

An observational study on diagnoses of 3,233 Gulf Veterans (Op Granby 1990-91) who attended the Ministry of Defence's Medical Assessment Programme 1993-2004

BACKGROUND: This is the result of an observational study on 3,233 Gulf veterans who have attended our medical assessment programme. We wanted to determine as a result of in-depth interviews, full medical examination and appropriate investigations, whether there was any unique Gulf war related medical condition. METHODS: Over a period of 10 years, 3,233 veterans have been assessed. All diagnoses have been made according to ICD-10 classifications. All psychiatric diagnoses have been confirmed by consultant psychiatrists. FINDINGS: 75% of veterans were well. Of the 25% unwell, 83% of ill health was accounted for by a psychiatric disorder. 3% of veterans had organic conditions which could be linked to Gulf deployment. The most common of these were respiratory disorders, followed by digestive disorders, injuries and skin disorders. Only 11 of these cases could be linked to the use of medical countermeasures. A further, 51 cases (41 respiratory disorders, 6 infections, 2 skin disorders and 2 eye conditions) could be linked to environmental conditions. INTERPRETATION: All veterans seen with health problems could be identified as per ICD-10 classification of disease. We did not find any medically unexplained conditions. We found no evidence of a unique 'Gulf War Syndrome'.     

Self-reported health of Persian Gulf War veterans: a comparison of help-seeking and randomly ascertained cases

The objective of this study was to compare self-selected Persian Gulf War veterans attending a health assessment program with veterans ascertained in an epidemiological study to determine why Gulf War veterans do, or do not, present for clinical assessment. A postal survey was sent to randomly selected United Kingdom Armed Forces personnel who served in the Persian Gulf conflict. Outcome measures included a symptom checklist, health perception, physical functioning, psychological distress, post-traumatic stress symptoms, and health attributions. A total of 173 survey respondents had also attended the Medical Assessment Program (MAP). MAP attendees were more likely to be female, older, and working part time or not working at all. They had poorer health perception and reported higher levels of illness, and they differed in terms of their health attributions. The belief that one had Gulf War syndrome and attributing health problems to Gulf War service were the most powerful predictors of MAP attendance, even when controlling for the level of physical functioning. The findings suggest that health beliefs rather than symptoms are more important predictors of attendance of an assessment program and that Gulf War veterans who attended the MAP have different characteristics than those who did not. This suggests that MAP patients are unrepresentative of the wider deployment to the Persian Gulf.     

Long-term effects of military service on mental health among veterans of the Vietnam War era

Comparing outcomes of veterans who served in Vietnam and those who served elsewhere, we examined treatment of post-traumatic stress disorder, treatment of other mental health conditions, psychiatric treatment location, and six mental health well-being measures. The analytic sample consisted of nationally representative data from the 2001 National Survey of Veterans. Analyses included multivariate logistic regression that controlled for sociodemographic characteristics. Of Vietnam War-era veterans in the National Survey of Veterans (N = 7,914), 3,937 served in Vietnam and 3,977 served elsewhere. These veterans were stratified into < 60 years of age (N = 6,141) and > or = 60 years of age (N = 1,766). Veterans who served in Vietnam had notably poorer mental health than did those who served elsewhere. There were striking mental health differences between younger and older veterans; younger veterans had substantially worse measures of mental health. These results suggest greater resource needs among younger Vietnam War veterans. Clinicians and the Department of Veterans Affairs should focus on mental health services for younger veterans.     

Prevalence of reported pain, widespread pain, and pain symmetry in veterans of the Persian Gulf War (1990-1991): the use of pain manikins in Persian Gulf War health research

The reporting of pain was compared for U.K. Persian Gulf War veterans, veterans from the Bosnian conflict, and personnel employed in the military at the time of the Persian Gulf War but not deployed (era comparison group). Pain manikins were used to assess the prevalence of the reporting of pain in different body sites and the prevalence of the reporting of widespread pain, in relation to comparison samples. Data from > 8,195 veterans were collected from a previously reported, cross-sectional, population-based, postal questionnaire survey. A greater proportion of Persian Gulf War veterans reported pain in the majority of the 25 areas of the body, compared with the Bosnia and era comparison groups. A greater proportion of Persian Gulf War veterans also fulfilled American College of Rheumatology criteria for widespread pain, compared with the Bosnia and era comparison groups (odds ratio, 1.82; 95% confidence interval, 1.51-2.20). Participants were much more likely to report pain in an opposite limb if pain was reported in the first limb (odds ratio, 36.9; 95% confidence interval, 31.7-43.0). Widespread pain was also more prevalent in the Persian Gulf War veteran sample compared to the comparison groups. Several years after the end of the Persian Gulf War, veterans still report pain. The mechanisms of this remain unclear. Implications for baseline monitoring of the health of military personnel are discussed.     

Health-related quality of life in Persian Gulf War Veterans.

OBJECTIVE: The objective of this investigation is to describe the health-related quality of life of Persian Gulf War (GW) veterans and to examine the effects of current chronic medical conditions and psychiatric status on physical functioning. METHODS: To measure health-related quality of life, the Medical Outcomes Short Form Survey (SF36) was administered approximately 4 years after the GW to a stratified, random sample of New England-area GW-deployed veterans and a group of military personnel deployed to Germany during the GW. The SF36 scores for the GW-deployed study population (N = 141) were compared with those for the Germany-deployed group (N = 46) and with published U.S. population norms. Multiple linear regression analyses were performed to identify risk factors associated with lower physical health functioning in the GW-deployed study group. RESULTS: Functional health status was significantly lower in the GW-deployed group compared with the Germany-deployed group for each of the SF36 subscales and the two summary scores (Physical Component Summary [PCS] and Mental Component Summary). Compared with the general U.S. population, the GW-deployed group median was between the 25th and 50th percentile for the Physical Functioning subscale and the PCS score. Within the GW-deployed group, lower education, psychological symptomatology, and a higher number of chronic self-reported medical conditions were significant predictors of the PCS score. CONCLUSION: GW-deployed veterans report lower functional health status compared with a group of Germany-deployed veterans and published general U.S. population norms. Within the group of GW-deployed veterans, several current medical and psychological conditions predictive of lower physical functioning levels were identified.     

Minnesota Multiphasic Personality Inventory-2 validity patterns: an elucidation of Gulf War syndrome

The potential effects of psychological distress on physical symptoms observed in Persian Gulf War veterans were evaluated in 48 veterans using neuropsychological evaluation that included personality assessment (the Minnesota Multiphasic Personality Inventory-2). Cluster analysis of the validity scales resulted in a solution with two viable subgroups. Members of cluster 1 had significantly higher scores on five Minnesota Multiphasic Personality Inventory-2 clinical scales, a measure of trait anxiety, and a number of subjective complaints, as well as lower scores on a task of attention. Neuropsychological functioning did not otherwise differ between the groups, Contributions of personality style in coping with physical and mental health stressors were indicated. Experience of distress appeared to be attributable to individual differences rather than factors that have been associated with the elusive Gulf War syndrome. Persian Gulf War veterans' emotional reactions to clinical laboratory findings, perceptions of exposure risks, war experience, and stress may represent a variation of post-traumatic stress disorder.     

Health and functioning among four war eras of U.S. veterans: examining the impact of war cohort membership,socioeconomic status,mental health,and disease prevalence

This analysis examines the self-rated health and functioning of World War II, Vietnam era, Korean Conflict, and Persian Gulf War veterans participating in the Veteran Identity Program Survey 2001. The results indicate that although World War II veterans are more likely to report poor health status and functioning, Vietnam-era veterans report more difficulty with specific activities of daily living and instrumental activities of daily living than any other era of veterans. These relationships remain when controlling for race/ethnicity, socioeconomic status, disease prevalence, and mental health status. These findings suggest that there are characteristics unique to the Vietnam experience that negatively affect this cohort of veterans. We suggest that further analysis examine the specific pathways through which the experience of being a Vietnam veteran affects health. In the meantime, health and social service planning within the Department of Veterans Affairs should explore the services that should be developed and targeted to this cohort of veterans so that they may remain independent in the community.     

Mental health status in veterans residing in rural versus non-rural areas:results from the veterans'health study

Background:The majority of Veterans Affair(VA)hospitals are in urban areas.We examined whether veterans residing in rural areas have lower mental health service use and poorer mental health status.Methods:Veterans with at least 1 warzone deployment in central and northeastern Pennsylvania were randomly selected for an interview.Mental health status,including posttraumatic stress disorder(PTSD),major depression,alcohol abuse and mental health global severity,were assessed using structured interviews.Psychiatric service use was based on self-reported utilization in the past 12 months.Results were compared between veterans residing in rural and non-rural areas.Data were also analyzed using multivariate logistic regression to minimize the influence by confounding factors.Results:A total of 1730 subjects(55％of the eligible veterans)responded to the survey and 1692 of them had complete geocode information.Those that did not have this information(n=38),were excluded from some analyses.Veterans residing in rural areas were older,more often of the white race,married,and experienced fewer stressful events.In comparison to those residing in non-rural areas,veterans residing in rural areas had lower global mental health severity scores;they also had fewer mental health visits.In multivariate logistic regression,rural residence was associated with lower service use,but not with PTSD,major depression,alcohol abuse,and global mental health severity score after adjusting confounding factors(e.g.,age,gender,marital status and education).Conclusions:Rural residence is associated with lower mental health service use,but not with poor mental health in veterans with former warzone deployment,suggesting rural residence is possibly protective.     

JP-8 jet fuel exposure and divided attention test performance in 1991 Gulf War veterans

INTRODUCTION: Previous research indicates that a large cohort of veterans from the 1991 Gulf War report polysymptomatic conditions. These syndromes often involve neurocognitive complaints, fatigue, and musculoskeletal symptoms, thus overlapping with civilian illnesses from low levels of environmental chemicals, chronic fatigue syndrome, and fibromyalgia. METHODS: To test for time-dependent changes over repeated intermittent exposures, we evaluated objective performance on a computerized visual divided attention test in chronically unhealthy Gulf War veterans (n = 22 ill with low-level chemical intolerance (CI); n = 24 ill without CI), healthy Gulf War veterans (n = 23), and healthy Gulf War era veterans (n = 20). Testing was done before and after each of three weekly, double blind, low-level JP-8 jet fuel or clean air sham exposure laboratory sessions, including acoustic startle stimuli. RESULTS: Unhealthy veterans receiving jet fuel had faster mean peripheral reaction times over sessions compared with unhealthy veterans receiving sham clean air exposures. Unhealthy Gulf veterans with CI exhibited faster post- vs. pre-session mean central reaction times compared with unhealthy Gulf veterans without CI. Findings were controlled for psychological distress variables. DISCUSSION: These data on unhealthy Gulf veterans show an acceleration of divided attention task performance over the course of repeated low-level JP-8 exposures. The present faster reaction times are consistent with rat neurobehavioral studies on environmental toxicant cross-sensitization and nonlinear dose-response patterns with stimulant drugs, as well as some previous civilian studies using other exposure agents. Together with previous research findings, the data suggest involvement of central nervous system dopaminergic pathways in affected Gulf veterans.     

Medical follow-up of Persian Gulf War Veterans with severe medically unexplained fatigue: a preliminary study.

An important question for researchers interested in long-term consequences of military service is the health outcome of symptomatic Persian Gulf War Veterans. From an original group of 76 Gulf War Veterans who received the diagnosis of severe fatiguing illness, we attempted to get 58 veterans to return to our center for a second evaluation. Thirteen returned. Two had recovered by the time of revisit, but the rest remained ill; however, only one was so ill as to be unable to work. The data suggest that the medical consequences of serving in the Persian Gulf are not transient. The difficulty in getting veterans to return to our center suggests potential problems in the proposed nation-wide longitudinal health outcome study of Persian Gulf War Veterans.