Identification of Gulf War Illness (GWI) Biomarkers

Research studies conducted over the last decade provide compelling evidence that Gulf War
Illness (GWI) may have been caused by exposure to chemicals, such as an anti-nerve agent
pyridostigmine bromide (PB) and different types of pesticides (GW agents). These studies also
show that brain structures that are involved in processing and storing memory, as well as
brain pathways involved in controlling pain and fatigue, are altered in GW veterans with this
condition. Even now, nearly 25 years later, veterans with GWI continue to experience these
complex symptoms and this illness remains difficult to diagnose since the current GWI
diagnostic process are limited by having to use information on self-reporting of symptoms. As
such, there remains a need for developing minimally invasive blood based disease markers
(biomarker) of GWI. The goal of this current study is to identify novel biomarkers of GWI
which can assist physicians in providing an objective diagnosis of GWI so that appropriate
clinical evaluations and treatments can be provided to GW veterans with this condition.
Another key goal of this project is to identify biomarkers of GW chemical exposure and
symptom profiles so that care and treatment can be tailored individually for each veteran
with GWI. Scientists working in the field of GWI research continue to provide strong evidence
that this condition is connected with irregular responses by blood cells which generally
combat irritations or other injuries to the body (inflammation). Scientists have also found
that GWI could also be due to damage to mitochondria, known as the powerhouses responsible
for generating energy through the breakdown of sugars and fats (lipids).

Scientists at the Roskamp Institute have developed mouse models of GWI in order to identify
biomarkers of brain damage and neurobehavioral problems that are a direct consequence of
chemicals to which GW veterans were exposed during the 1991 GW. They have identified that
there might be problems with breaking down fats in the brains of exposed mice even long after
subacute exposure to GW agents. In particular, they show changes in lipids which belong to
cellular compartments (peroxisomes) that perform tasks similar to those of the mitochondria
with respect to the breakdown of fats. The inflammatory processes, mitochondria and
peroxisomes display unique lipid classes that can be measured in blood using mass
spectrometry technologies. These technologies allow us to detect and measure elemental
composition of each lipid. We plan to use this technology to study lipids that are specific
to inflammation and metabolic disturbances associated with GWI in order to determine if they
can be used as biomarkers of GWI. In collaboration with the Boston GWI consortium, we are
testing this hypothesis and our early pilot work in control and GWI veterans support
potential use of these lipids as biomarkers of GWI. The proposal will expand these pilot
studies and determine if lipids associated with these key disturbances in GWI can be useful
tools for diagnosing GWI. The proposal will also try to use these lipids in order to identify
subgroups of GW veterans with similar chemical exposures and symptom patterns. This work will
also be facilitated by the use of blood samples from GWI animal models that will help with
translational studies linking animal model work and human studies. This will help fill the
gaps between the two so that future studies can be conducted that can use these biomarkers to
determine if treatments and care designed for GWI are succeeding.

Furthermore, identifying biomarkers of exposures and symptom profiles which will help with
delivering personalized care and treatment to each veteran appropriately. The existing
expertise and collaborations between the Roskamp Institute and the Boston GWI consortium will
expedite successful translation of this endeavor so that appropriate biomarker tools are made
available to the clinicians in order to assist them with diagnosing GWI and ensuring that
appropriate medical plans are developed for the care and treatment of veterans with GWI.

Inclusion Criteria:

1. Age 35 years or older 2. Served in the 1990-1991 Gulf War 3. Ability to understand
written and spoken English or availability of a legal representative who can understand
written or spoken English. Participants and caregiver/informants must be able to read,
write and speak the language in which psychometric tests are provided with visual and
auditory acuity (corrected) sufficient to allow for accurate testing.

Exclusion Criteria:

1. Diagnosed or being treated by a physician for any of the following (Steele et al,
2000) and deemed clinically significant per the discretion of the PI:

2. Cancer (except for non-melanoma skin cancers)

3. Chronic infectious disease

4. Problems resulting from postwar injuries.

5. Liver disease

6. Lupus

7. Multiple sclerosis

8. Stroke

9. Serious psychiatric condition (those associated with psychosis and/or for which the
respondent had been hospitalized since 1991).

10. Hospitalized in the last 5 years for alcohol or drug dependence, depression, or
post-traumatic stress disorder (PTSD).

11. Diagnosis of Dementia of any type or Parkinson's disease