In World War I, they called it "shell shock," which the brass of that day tended to denigrate as a mental form of desertion.
By World War II, the disorder was known, somewhat more analytically, as "combat fatigue." In and after Vietnam, the condition became "post-traumatic stress disorder" (PTSD).
Now, Desert Storm and its aftermath have spawned "Gulf War Syndrome" (GWS), a variant of PTSD.
"This is reported to involve an array of neurocognitive and mood problems," observed Stanford University molecular neurobiologist Robert Sapolsky, as well as "joint pain, inflammation, pulmonary complications and chronic fatigue."
Assuming for the sake of argument that GWS actually exists as a medical entity — and that argument still rages — Sapolsky perceives two dichotamous viewpoints as to the origins of the disease.
Gulf War veterans blame their disabilities on the biological and chemical weapons detonated in the theatre, toxic fumes from burning oilfields, and in particular the acetylcholinesterase-inhibiting pyridostigmine tablets issued to all allied combatants as experimental prophylaxis for presumed Iraqi nerve gas.
"In contrast," Sapolsky pointed out, "the U.S. government has doubted the legitimacy of the GWS, suggesting that if it exists at all, it is psychosomatic, i.e. stress-related."
Some of the international troops that gulped down their anti-nerve-toxin pills — including 213 Israeli soldiers on nerve-gas alert inside Israel — complained of side effects, such as headaches, insomnia, drowsiness, nervousness, unfocussed attention span, all specific to the central nervous system. (See BioWorld Today, Dec. 3, 1996, p. 1)
Sapolsky is the author of an editorial in today's issue of Nature, dated May 28, 1998, titled "The stress of Gulf War syndrome."
It comments on an accompanying research paper headed "Acute stress facilitates long-lasting changes in cholinergic gene expression." That article's senior author is molecular biologist Hermona Soreq, a professor at the Hebrew University of Jerusalem, in Israel. (Her work is partially supported by grants from the U.S. Army Medical Research and Development Command.)
Mice Keep Heads Above Water; Stressed Neurons Inside
Sapolsky surmises, however, that the Israeli research "is mostly driven by the basic neurological science, with Gulf War issues somewhat secondary. Their aim is to understand the regulation of this neurotransmitter, acetylcholine, its synthesis, its degradation, and what sort of factors will modulate its efficacy."
To model acute stress in humans, Soreq and her co-authors placed mice in a small swimming pool, and made them swim for their lives.
"Essentially they did two parallel studies," Sapolsky told BioWorld Today in an interview. "One was exposing rodents to stress. The other was exposing autopsied brain tissue of stressed rodents to cholinesterase inhibitors, and seeing that both stressors were doing similar things. Both of these novel observations," he added, "were causing the long-term disruption of acetylcholine levels."
In her paper, Soreq reported that "acetylcholinesterase activity in the brain's neocortex and hippocampus, but not cerebellum, of animals exposed to a single stress session increased by two- to three-fold within 50 minutes after stress, and cortical activity remained significantly higher than that in control mice for over 80 hours after a swim."
"Cortex and hippocampus," Sapolsky pointed out, "are two major hot spots for memory."
He acclaimed the novelty of the Israeli findings "that these acetylcholinesterase inhibitors cause this long-term suppression of levels of this neurotransmitter, which plays a role in memory, and in parallel that stress causes this suppression. Both of these," he commented, "were novel findings, as were the intervening mechanisms that they found."
Apropos, an acetylcholinesterase inhibitor, Cognex, is FDA-approved as a treatment for failing memory in Alzheimer's disease (AD) patients. Deficits of acetylcholine in the AD brain are thought to be linked to cognitive impairments of memory, language, learning and the ability to perform everyday activities.
Sapolsky's read on this application "is that statistically one can show significant neurological effects, but how much that has impact on the quality of life of an individual with AD is not a lot to write home about."
He suggested that "it's going to be mighty hard for people who are at all oriented toward the Gulf War Syndrome stuff to read 'cholinesterase inhibitors' without saying, 'My God, that's the same drug they used out there!"
Gulf War Syndrome: Dichotomy — Or Synergy?
As for the GWS debate between a toxic vs. a stress origin for the syndrome, Sapolsky made the point that "you may not have to choose between the stress argument and the toxin argument. It is well documented that stress exacerbates various neurotoxins, and there may be an interaction — in fact, a synergy — between the two.
"Unfortunately," he mused, "the Israeli findings will probably only fuel (rather than resolve) the debate over the causes of Gulf War syndrome."
His own lab at Stanford focuses on "the ways in which stress and stress hormones can impair the ability of the neurons to survive neurological insult."
He concluded by stressing "how incredibly early steps these Israeli results report. There are mice; there are rodent brain slices. It's not clear how either variable could have effects that last years in a human, compared with just 80 hours in mice." *