• Although further investigations based solely on self-reports are not likely to contribute significantly to increased understanding of Gulf War illness, well-designed follow-up studies of mortality, cancer, and neurologic and psychiatric outcomes will continue to be valuable. Well-designed, adequately powered studies of MS and ALS incidence following deployment are also needed.

  • Methodologically robust cohorts need to be assembled now and followed carefully to track the development of ALS, MS, brain cancer, and psychiatric conditions, as well as the appearance of additional health issues that occur at a later age, such as other cancers, cardiovascular disease, and neurodegenerative diseases. Several well-characterized cohorts have already been established that could form the basis of future studies. For example, the US cohort studied by the VA; the two UK cohorts; and the Canadian, Danish, and Australian cohorts. Relatively small cohorts, such as the Canadian or Australian veterans, might not be useful for outcomes with low incidence (for example, ALS or brain cancer), but they might be very useful for tracking frequently seen health outcomes such as Gulf War illness, cardiovascular and respiratory diseases, other cancer types, neurodegenerative conditions such as dementia, and some psychiatric disorders.

  • With regard to functional gastrointestinal disorders (irritable bowel syndrome and functional dyspepsia), recent evidence supports the need for two types of studies: one type will determine the role of prior acute gastroenteritis among deployed soldiers in the development of these disorders, and the second type will use symptom-specific criteria (for example, Rome criteria) to clarify the association of medical and psychosocial comorbidities with functional gastrointestinal disorders and their severity.

  • Uncommon genetic variants or rare environmental events may not be recognized as associated with an outcome of interest unless very large numbers of individuals are studied or sophisticated capture methods are used to explore specific hypotheses. It is possible, for example, that new and objective information related to exposures might become available in the future that could improve our ability to estimate individual exposures and to assess health effects in groups of Gulf War veterans according to specific exposures.

In addition to epidemiologic studies, the committee believes that a second branch of inquiry is important. This consists of a renewed research effort with substantial commitment to well-organized efforts to better identify and treat multisymptom illness in Gulf War veterans. Given the high reported prevalence of persistent symptoms, plus the steady advances in understanding genetics, molecular diagnostics, and imaging, it is possible now to plan and carry out adequately powered studies to identify inherited genetic variants, molecular profiles of gene expression, other epigenetic markers (such as modifications of DNA structure related to environmental exposures), specific viral exposures, signatures of immune activation, or brain changes identified by sensitive imaging measures—all these are traits that distinguish Gulf War veterans with persistent medical symptoms from healthy deployed or nondeployed veterans. The committee is optimistic that a rigorous, adequately powered analysis would identify useful biomarkers that might not only be helpful for symptomatic veterans of the Gulf War but also for nondeployed veterans and for civilians with a range of medically unexplained symptoms including chronic fatigue, muscle and joint pains, sleep disturbances, difficulty with concentration, and depression.

As with many other disorders, it is likely that Gulf War illness results from an interplay of genetic and environmental factors; genetics may play a larger role for some affected



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