Cardiovascular Stress Responses and Their Relation to Symptoms in Gulf War Veterans With Fatiguing Illness ARNOLD PECKERMAN,PHD, JOHN J. LAMANCA,PHD, SHARON L. SMITH, BA, ANDRE TAYLOR, MD, LANA TIERSKY,PHD, CLAUDIA POLLET, MD, LEO R. KORN,PHD, BARRY E. HURWITZ,PHD, JOHN E. OTTENWELLER,PHD, AND BENJAMIN H. NATELSON, MD Objective: The objective of this study was to examine whether inappropriate cardiovascular responses to stressors may underlie symptoms in Gulf War veterans with chronic fatigue. Methods: Psychophysiological stress testing was performed on 51 Gulf War veterans with chronic fatigue (using the 1994 case definition of the Centers for Disease Control and Prevention) and 42 healthy veterans. Hemodynamic responses to cold pressor, speech, and arithmetic stressors were evaluated using impedance cardiography. Results: Veterans with chronic fatigue had diminished blood pressure responses during cognitive (speech and arithmetic) stress tests due to unusually small increases in total peripheral resistance. The cold pressor test, however, evoked similar blood pressure responses in the chronic fatigue and control groups. Low reactivity to cognitive stressors was associated with greater fatigue ratings among ill veterans, whereas an opposite relation was observed among healthy veterans. Self-reported neurocognitive decline was associated with low reactivity to the arithmetic task. Conclusions: These results suggest a physiological basis for some Gulf War veterans’ reports of severe chronic fatigue. A greater deficit with responses processed through cerebral centers, as compared with a sensory stimulus (cold pressor), suggests a defect in cortical control of cardiovascular function. More research is needed to determine the specific mechanisms through which the dissociation between behavioral and cardiovascular activities identified in this study may be contributing to symptoms in Gulf War veterans. Key words: Gulf War illnesses, chronic fatigue, cardiovascular stress response, impedance cardiography. AD ACL 5 Activation-Deactivation Adjective Check- list; BDI 5 Beck Depression Inventory; CDC 5 Centers for Disease Control and Prevention; CF 5 chronic fa- tigue; CFS 5 chronic fatigue syndrome; DBP 5 dia- stolic blood pressure; GV 5 Gulf War veteran; HR 5 heart rate; ICF 5 idiopathic chronic fatigue; MAP 5 mean arterial pressure; MFI 5 Multidimensional Fa- tigue Inventory; PEP 5 preejection period; POMS 5 Profile of Mood States; Q ˙ 5 cardiac output; SBP 5 systolic blood pressure; SV 5 stroke volume; TPR 5 total peripheral resistance. INTRODUCTION In the aftermath of the Persian Gulf War, a large number of veterans developed nonspecific health problems with no medical explanation (1). Among the symptoms most commonly reported by ill veterans are debilitating chronic fatigue, problems with memory and concentration, musculoskeletal pain, headache, and unrefreshing sleep (2– 4). This pattern of symp- toms closely resembles that of CFS, a chronic illness of undetermined etiologic and pathophysiological mech- anisms (5). As yet, no physiological or laboratory ab- normalities have been identified in GVs. One explana- tion for the difficulties with finding the causes of symptoms may be that the underlying pathophysiol- ogy involves subtle abnormalities in multiple organs (6). This view focuses attention on systemic functions such as circulation, abnormalities of which can have negative consequences throughout the body. Evidence of such abnormalities in patients with CFS has been reported (7, 8). The study reported here examined the possibility that a problem with circulation may underlie symp- toms in GVs meeting the case definition of CF (9). Our basic hypothesis was that GVs with CF have abnormal- ities in central regulatory mechanisms of blood pres- sure control that might result in an inadequate perfu- sion. To test this hypothesis, we examined whether hemodynamic responses to behavioral stressors were altered in GVs with CF. The study was designed to provide preliminary data on what types of challenges (cognitive vs. physical) and specific mechanisms (ie, those concerned with regulation of peripheral resis- tance vs. those regulating cardiac output) may be in- volved. In addition, the study examined whether changes in cardiovascular functioning in GVs with CF were consistent with major symptoms of this illness, including fatigue, cognitive abnormalities, and associ- ated functional decline. With respect to fatigue, our basic presumption was that lack of energy in ill veter- ans was caused by a disease and thus would have a From the Center for Environmental Hazards Research (A.P., J.J.L., S.L.S., A.T., L.T., C.P., L.R.K., J.E.O., B.H.N.), VA Medical Center, East Orange, NJ; Environmental and Occupational Health Sciences Institute (A.P.), Robert Wood Johnson Medical School, Piscataway, NJ; and Department of Psychology (B.H.), University of Miami, Coral Gables, FL. Address reprint requests to: Arnold Peckerman, PhD, Gulf War Research Center (127B), VA Medical Center, East Orange, NJ 07018- 1095. Email: apeckerm@nbunj.jvnc.net Received for publication November 19, 1998; revision received February 1, 2000. 509 Psychosomatic Medicine 62:509 –516 (2000) 0033-3174/00/6204-0509 Copyright © 2000 by the American Psychosomatic Society