More than 30 years after the 1991 Gulf War, veterans of this war continue to experience a number of debilitating symptoms collectively known as Gulf War Illness (GWI).

About 200,000 veterans—roughly one-third of troops deployed during this war—are suffering from largely invisible symptoms ranging from chronic pain and fatigue, to respiratory and gastrointestinal issues, memory problems and chronic headaches. Multiple studies have linked these persistent symptoms to military service during the Gulf War, and current evidence indicates that these health issues were caused by exposure to toxic chemicals, including sarin nerve gas, pesticides, and pyridostigmine bromide pills meant to protect soldiers from nerve gas during deployment. This type of chemically-induced illness has been termed ‘toxic wounds.’

Kimberly Sullivan, research associate professor of environmental health, is a leading expert of this research on GWI and served for nearly 10 years as the principal investigator and director of the former Gulf War Illness Consortium, a multi-institutional initiative based at the School of Public Health and funded by the Department of Defense’s Gulf War Illness Research Program (GWIRP), that aimed to identify GWI biomarkers to improve diagnosis and develop targeted treatments for ailing Gulf War veterans.  

Now, a new study that Sullivan led provides an in-depth assessment of the core clinical work of the GWIC, which focused on understanding the brain and immune functions of veterans with Gulf War Illness.

Published in the journal Brain Sciences, the study found that veterans with GWI continue to show higher rates of chronic health issues such as memory problems, chronic pain, debilitating fatigue, and gastrointestinal  problems. The study also showed evidence that many GW veterans are experiencing an earlier onset of age-related chronic diseases such as hypertension. Sullivan and colleagues also found that the extended use of pesticides on the skin and sustaining a mild traumatic brain injury during the war greatly increased the risk of having GWI. The researchers found no association between war experiences associated with intense stress or trauma and the risk of developing GWI.

“These results clearly show that GWI was not a result of stressors such as combat exposure, but rather are due to toxic wounds from exposures during the war that affect the brain and appear to be additive,” Sullivan says. “We believe these types of combined exposures, or ‘multiple-hits’ to the brain, as well as potential genetic susceptibility, may be why some veterans developed chronic GWI symptoms after these exposures, while others did not.”

For the study, the researchers collected and analyzed data on the health of 269 Gulf War veterans, through clinical evaluations, immune and immunogenetic blood tests, neuropsychological testing, and brain imaging at Boston University, the Miami Department of Veterans Affairs Medical Center, and Baylor College of Medicine between 2015 and 2020. The team also conducted a series of standardized health assessments including pain, fatigue, sleep and mood outcomes, and performed neuroimmune blood testing.

In addition to the aforementioned health issues, when compared to healthy GW controls, veterans with GWI scored worse on general health, sleep quality, sinus conditions, depression, and post-traumatic stress disorder (PTSD). For example, 42 percent of GW cases reported respiratory or sinus issues, compared to 7 percent of controls; 70 percent of cases reported body pain, versus 4 percent of controls; 83 percent had trouble finding words when speaking, versus 35 percent of controls; and 23 percent of cases experienced chronic fatigue syndrome, versus 2 percent of controls and 31 percent of cases experienced irritable bowel syndrome versus 7 percent of controls. Either currently or during their lifetime, 44 percent of GWI cases struggled with major depression versus 24 percent of controls Importantly, veterans who reported extended use of pesticides on their skin during deployment were 3 times more likely to have GWI and those who reported sustaining a mild head injury during the war were 7 times more likely to have GWI.

Despite these signs of poor health, veterans with GWI reported normal health indicators on standard physical evaluation and clinical diagnostic tests for the study, which the researchers say could contribute to why GWI was unrecognized and undiagnosed by veterans’ physicians for so many years.

These results underscore the need for continued research on GWI to identify biomarkers and develop objective health measures for diagnosis, rather than only rely on the current method of self-reporting of symptoms, Sullivan says.

“Without objective biomarkers and diagnostic tests, it has made it much harder for Gulf War veterans to have official recognition of the disease and its causes, and has left many veterans struggling to get VA benefits for these self-reported symptoms,” she says. “Over 80 percent of Gulf War veteran claims for GWI are still being denied, and veterans feel that they have not been taken seriously about their illness.”

Through their research, Sullivan says the team can now predict which veterans meet GWI criteria with about 71-90 percent accuracy based on blood, genetic and brain imaging marker testing from GWIC samples.

“We are working to revise the case definitions to include some of these simple diagnostic markers,” she says. “We hope that this will help to validate their illness and to get our veterans the help that they need. It’s our responsibility to take care of our veterans who went to war and came back sick.”

Since 2019, Sullivan has advanced the work of the GWIC through the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN), a four-site recruitment and 10-site data-mining project that serves as a repository and critical resource for GWI researchers. Funded by the GWIRP, the $3.2 million project houses previous (including GWIC) and newly collected biological specimens and clinical survey and brain imaging data from 500 veterans with GWI and 267 healthy control veterans.

A recent study published in the journal Life Sciences details the work of BBRAIN thus far. Sullivan says the team is working to improve the accuracy of their diagnostic markers with the addition of the larger BBRAIN samples and data.

“We have learned from the GWIC study that combined exposures to toxic pesticides and even mild brain injuries are important to lasting health symptoms in our veterans,” says Sullivan. “More focused survey questions regarding these types of exposures are now included in the BBRAIN survey so that we can better identify the cause of the illness and to avoid these types of toxic wounds in future deployments. We hope to finalize study recruitment in the next year to be able to more fully answer these questions and to provide our veterans with simple diagnostic tests for their illness.”

If you are interested in participating in the BBRAIN study, please call project coordinator Dylan Keating at 617-358-2230 or email at bbrain@bu.edu.