PSYCHOPHYSIOLOGICAL STUDIES IN GULF WAR VETERANS
Iris R. Bell, M.D., Ph.D.
Program in Integrative Medicine, University of Arizona College of Medicine, Tucson, AZ
Previous studies have shown that a large percentage of Gulf War veterans endorse multiple symptoms in multiple systems, e.g., fatigue, skin rashes, headaches, musculoskeletal pain, and memory loss, at increased rates. Ill Gulf veterans also report acquired low level chemical odor intolerance (CI) at higher rates than do healthy Gulf or Era veterans (Bell et al. 1998).
Decreased heart rate variability is a nonspecific biomarker of reduced adaptability across various disorders, including fibromyalgia (which occurs at increased rates in ill Gulf veterans), multiple sclerosis, lupus, cardiac disease, and posttraumatic stress disorder. The sensitization model for CI (Bell et al 1999) suggests that ill Gulf veterans, especially those with CI, should show progressive amplification of adverse effects on heart rate variability of repeated low level chemical exposures to a salient stimulus (JP-8 jet fuel) as well as cross-sensitization to subsequent perfume exposures in the laboratory.
The present study compared 4 groups of U.S. military veterans (mean age 40 SD 8 yrs, 85% male): ill Gulf veterans with CI, ill Gulf veterans without CI, healthy Gulf veterans, healthy Era veterans (served in military at same time but never deployed to Gulf region). The design was a parallel groups, randomized, double-blind assignment to either 3 sessions of repeated subolfactory threshold levels of JP-8 jet fuel or 3 sessions of repeated clean air (sham) exposures. All groups and subgroups received detectable perfume exposures in session 4. Sessions were spaced 1 week apart. Subjects also underwent cognitive testing with the computerized visual divided attention test (DAT), which has shown replicable performance differences between civilians with and without CI.
At Session 1 baseline, groups did not differ for resting heart rate, blood pressure, mean interbeat interval, standard deviation of the interbeat interval (SD IBI = heart rate variability), or eyeblink rate. The ill Gulf veterans with CI exhibited significantly slower central reaction times than did healthy Era veterans on the DAT at baseline. The patterns of change for SD IBI over sessions were complex and different between groups as a function of JP-8 versus sham exposures. The ill Gulf veterans with CI showed the predicted sensitization pattern to JP-8, with the lowest SD IBIs (poorest heart rate variability) of all groups. Statistical analyses using general linear and random effects regression models indicated that the two ill Gulf groups combined differed significantly from healthy Gulf veterans in their SD IBI patterns as a function of JP-8 exposure vs sham over sessions, even after controlling for age, ethnicity, sex, and psychological disturbance on the MMPI subscales.
We then evaluated the divergence between observed and expected values of SD IBI for perfume exposure as a function of prior JP-8 versus clean air (sham) exposures in the laboratory. Values close to expected would reflect a slope similar to that seen over the first 3 sessions. Notably, with perfume, the groups except the ill Gulf veterans without CI and healthy Era veterans diverged significantly from both their prior JP-8 exposure and their sham response patterns. Only healthy Era veterans showed statistically comparable changes in their perfume responses regardless of having received JP-8 or clean air sham in the prior three sessions. Notably, the direction of response in the ill Gulf veterans without CI and the healthy Gulf veterans was opposite for their respective JP-8 and sham-exposed subgroups, consistent with exposure-dependent and intensity-dependent oscillatory effects observed in animal studies by Antelman and Caggiula (1996; 1998).
Taken together, the data suggest that ill Gulf veterans with CI have impaired divided attention task performance and that ill Gulf veterans with and without CI differ from healthy Gulf veterans in their pattern of change in heart rate variability over time as a function of repeated JP-8 jet fuel exposures vs sham (clean air). Prior exposures to JP-8 vs clean air influence the nature of the subsequent response to perfume in all Gulf veterans, ill or healthy, with and without CI, though the direction of the response varies between groups.
References
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Bell IR, , Warg-Damiani L, Baldwin CM, Walsh M, Schwartz GE. Self-reported chemical sensitivity and wartime chemical exposures in Gulf War veterans with and without decreased global health ratings. Military Medicine 1998; 163:725-732.
Caggiula AR, Antelman SM, Kucinski BJ, Fowler H, Edwards DJ, Austin MC, Gershon S, Stiller R. Oscillatory sensitization model of repeated drug exposure: cocaine’s effects on shock-induced hypoalgesia. Prog NeuroPsychopharmacol Biol Psychiatry 1998; 22:511-521.
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