Categories
Health & Medicine Mind & Brain

Chemical exposure now linked to Gulf War syndrome

The following story published March 20, 2009 on www.sciencedaily.com

A new study by researchers from UT Southwestern Medical Center and Southern Methodist University is the first to pinpoint damage inside the brains of veterans suffering from Gulf War syndrome. The finding links the illness to chemical exposures and may lead to diagnostic tests and treatments.

Robert Haley, chief of epidemiology at UT Southwestern and lead author of the study, said the research uncovers and locates areas of the brain that function abnormally. Recent studies had shown evidence of chemical abnormalities and shrinkage of white matter in the brains of veterans exposed to certain toxic chemicals, such as sarin gas during the 1991 Persian Gulf War.

gunst.jpgThe research, was published in the March issue of the journal “Psychiatry Research: Neuroimaging.” Imaging enables investigators to visualize exact brain structures affected by these chemical exposures, Haley said.

Richard Gunst, Wayne Woodward and William Schucany, professors in SMU’s Statistical Science Department in Dedman College, are collaborating with the imaging specialists at UT Southwestern Medical Center to compare brain scans of veterans with the syndrome against a healthy control group.

“Before this study, we didn’t know exactly what parts of the brain were damaged and causing the symptoms,” Haley said.

Richard Gunst

“We designed an experiment to test areas of the brain that would have been damaged if the illness was caused by sarin or pesticides, and the results were positive,” he said.

In designing the study, Haley and his colleagues reasoned that if low-level sarin or pesticides had damaged Gulf War veterans’ brains, a likely target of the damage would be cholinergic receptors on cells in certain brain structures. If that was so, administering safe levels of medicines that stimulate cholinergic receptors would elicit an abnormal response in ill veterans.

ww2.gifIn the study, 21 chronically ill Gulf War veterans and 17 well veterans were given small doses of physostigmine, a substance which briefly stimulates cholinergic receptors. Researchers then measured the study participants’ brain cell response with brain scans.

Pictured right: Wayne Woodward

“What we found was that some of the brain areas we previously suspected responded abnormally to the cholinergic challenge,” Haley said. “Those areas were in the basal ganglia, hippocampus, thalamus and amygdala, and the thalamus. Changes in functioning of these brain structures can certainly cause problems with concentration and memory, body pain, fatigue, abnormal emotional responses and personality changes that we commonly see in ill Gulf War veterans.”

A previous study funded by the U.S. Army found that repetitive exposure to low-level sarin nerve gas caused changes in cholinergic receptors in lab rats.

“An added bonus is a statistical formula combining the brain responses in 17 brain areas that separated the ill from the well veterans, and three different Gulf War syndrome variants from each other with a high degree of accuracy,” Haley said. “If this finding can be repeated in a larger group, we might have an objective test for Gulf War syndrome and its variants.”

Schucany%202008.jpgAn objective diagnostic test, he said, sets the stage for ongoing genetic studies to see why some people are affected by chemical exposures, and why others are not.

New studies would also allow the selection of homogenous groups of ill veterans in which to run efficient clinical trials for treatments. Haley first described Gulf War syndrome in a series of papers published in January 1997 in the “Journal of the American Medical Association.”

William Schucany

In previous studies, research from Haley showed that veterans suffering from Gulf War syndrome had lower levels of a protective blood enzyme called paraoxonase, which usually fights off the toxins found in sarin.

Veterans who served in the same geographical area and did not get sick had higher levels of this enzyme.

Haley and his colleagues have closely followed the same group of tests subjects since 1995. In 2006, UT Southwestern and the Department of Veterans Affairs established a dedicated, collaborative Gulf War illness research enterprise in Dallas, managed by UT Southwestern.

Texas Sen. Kay Bailey Hutchison, a longtime supporter of Gulf War research, facilitated that agreement and secured a $75 million appropriation over five years for Gulf War illness research.

The study was funded, in part, by the U.S. Army Medical Research and Materiel Command.

Other UT Southwestern researchers involved in the study included Jeffrey Spence and Patrick Carmack, assistant professors of clinical sciences; Michael Devous and Frederick Bonte, professors of radiology; and Madhukar Trivedi, professor of psychiatry.

Related links:
Air Force Times: Study links Gulf War exposures, brain changes
SMU Profile: Patrick Carmack and Jeffrey Spence
Panel: Gulf War Syndrome is real
Gulf War Syndrome research overview
Richard Gunst
Wayne Woodward
William Schucany
Robert Haley
UTSouthwestern, Division of Epidemiology: Gulf War Associated Illnesses
SMU honors alumnus Robert Haley
SMU Department of Statistical Science
Explainer: Spatial statistical modeling
Dedman College of Humanities and Sciences

Categories
Mind & Brain

Deep brain mapping could pinpoint Gulf War Syndrome

Researchers at Southern Methodist University are pioneering the use of spatial statistical modeling to analyze brain scan data from Persian Gulf War veterans. The goal is to pinpoint specific areas of the brain affected by Gulf War Syndrome.

Richard Gunst, Wayne Woodward and William Schucany, professors in SMU’s Department of Statistical Science in Dedman College, are collaborating with imaging specialists at UT Southwestern Medical Center in Dallas to compare brain scans of veterans suffering from the syndrome with those of a healthy control group.

gunst.jpgThe SMU team is working with renowned UTSW epidemiologist Robert Haley, one of the foremost experts on the syndrome.

A congressionally mandated study has revealed that one of every four veterans of the 1991 Gulf War suffers from neurological symptoms collectively referred to as Gulf War Syndrome. The Research Advisory Committee on Gulf War Veterans’ Illnesses began work in 2002 and presented its lengthy report to Secretary of Veterans Affairs James Peake on Nov. 17.ww2.gifPersian Gulf War veterans from across the country are being tested at UTSW using a type of brain imaging called functional Magnetic Resonance Imaging, or fMRI.

Richard Gunst

The veterans are tested while performing tasks intended to activate specific regions of the brain.

Photo right: Wayne Woodward

The SMU team, which includes graduate students Patrick Carmack and Jeffrey Spence, is analyzing brain activation signals reflected from the multiple images taken of each subject’s brain. From that they’ll determine which variations occur naturally and which are due to the syndrome. Previous analyses have been unable to separate real distinctions from “noise.”

Schucany%202008.jpgThe SMU team’s primary challenge is in identifying differences in brain activation from locations deep within the brain using measured brain signals that are weak and vary from location to location.

Spatial modeling uses information from neighboring locations to strengthen the weak signals in active brain locations so the signal can be detected as real.

“Spatial modeling in brain imaging is new,” Gunst said. “This has not been done the way we are doing it.”
William Schucany

Rapid technological advances in medical imaging of the human brain are imposing demands for new statistical methods that can be used to detect small differences between normal and dysfunctional brain activity, Gunst said. — Kim Cobb

Related links:
Air Force Times: Study links Gulf War exposures, brain changes
Panel: Gulf War Syndrome is real
Gulf War Syndrome research overview
Richard Gunst
Wayne Woodward
William Schucany
SMU Profile: Patrick Carmack and Jeffrey Spence
Robert Haley
UTSouthwestern, Division of Epidemiology: Gulf War Associated Illnesses
SMU honors alumnus Robert Haley
SMU Department of Statistical Science
Explainer: Spatial statistical modeling
Dedman College of Humanities and Sciences