Gulf War illness linked to nervous system damage

By Russell Rian

A UT Southwestern Medical Center-based study proves that Gulf War illness stems from damage to the body’s autonomic nervous system, which controls heart rate, sweating, digestion, sleep, and other bodily processes running in the background.

The study, based on a sample of 97 people selected for detailed neurologic testing from 8,020 representative Gulf War veterans, also confirmed high correlations between the symptoms of sick veterans and abnormalities in the cholinergic autonomic system that’s typically at work during periods of inactivity.

Robert Haley
Dr. Robert Haley (above) and Dr. Steve Vernino pinpointed damage to the autonomic nervous system in veterans with Gulf War syndrome through research at UTSW’s Autonomic Testing Lab.

“This really locates the basis for most of the symptoms and the reason the sick veterans have a hard time describing it – because it’s part of the nervous system that you’re not normally aware of,” said lead author Dr. Robert Haley, Professor of Internal Medicine and Chief of Epidemiology. “The control system for most bodily functions that you are not aware of is malfunctioning.”

The study, appearing online in JAMA Neurology (formerly Archives of Neurology), is the largest thus far among a series of studies attempting to track down autonomic nervous system abnormalities in those with Gulf War illness. 

Last year, Dr. Haley and colleagues validated a case definition of Gulf War illness, including the three important subtypes, or variants, a step that proved critical in discovering the neurological damage underlying the illness. Previous smaller studies by Dr. Haley and other UTSW researchers showed that symptoms such as chronic diarrhea, unrefreshing sleep, fatigue, and sexual dysfunction are due to autonomic dysfunctions in these veterans. 

The autonomic nervous system is divided into two essential parts: adrenergic receptors in the sympathetic nervous system that work during active modes, and cholinergic receptors in the parasympathetic nervous system that work during periods of sleep and inactivity.

The study found significant deficits in the parasympathetic system, or “rest and digest” functions, in those with Gulf War illness compared to control groups of both deployed and nondeployed healthy veterans, all selected randomly from a nationally representative sample. The most notable dysfunctions were with systems controlling digestion, sweating, and cooling systems, and intervals between heartbeats – all controlled by autonomic nerves classified as “cholinergic” since they use the neurotransmitter acetylcholine.

“They can be hard to track down because everyone’s autonomic system varies from day to day, so they are hard things to measure,” said senior author Dr. Steve Vernino, Academic Vice Chair and Professor of Neurology and Neurotherapeutics, head of the neuromuscular disorders division, and Director of the Autonomic Testing Lab. “The techniques we used have been well-established, although only a dozen medical centers are able to do those kinds of tests. The strength of the study was that it was done rigorously and that those abnormalities were significant.”

Researchers confirmed the autonomic disruptions in veterans with all three types of Gulf War illness and, as with previous studies, found the autonomic disturbances were most dramatic in veterans with Gulf War syndrome 2. This type has the most severe symptoms.

Prior studies supported by the U.S. Army Medical Institute for Chemical Defense found that repetitive, subsymptomatic exposure to low-level sarin nerve agent caused long-term damage to cholinergic receptors in the brains of rodents.  Also, previous studies by Dr. Haley’s group found chronic abnormal response of cholinergic receptors in the brains of ill Gulf War veterans and connected the illness with a difference in the PON1 gene that confers increased susceptibility to sarin.

Gulf War syndrome affects an estimated 25 percent of the 700,000 military personnel deployed in the 1991 Persian Gulf War.

Dr. Melanie M. Biggs, Associate Professor of Psychiatry, also worked on the study, which was funded by a federal research contract through the Dallas Veterans Affairs Medical Center and grants from the U.S. Army Medical Research and Materiel Command, and the National Institutes of Health.

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Dr. Haley holds the U.S. Armed Forces Veterans Distinguished Chair for Medical Research, Honoring America's Gulf War Veterans.

Dr. Vernino holds the Dr. Bob and Jean Smith Foundation Distinguished Chair in Neuromuscular Disease Research.