JP-8 jet fuel exposure and divided attention test performance in 1991 Gulf War veterans.

INTRODUCTION Previous research indicates that a large cohort of veterans from the 1991 Gulf War report polysymptomatic conditions. These syndromes often involve neurocognitive complaints, fatigue, and musculoskeletal symptoms, thus overlapping with civilian illnesses from low levels of environmental chemicals, chronic fatigue syndrome, and fibromyalgia. METHODS To test for time-dependent changes over repeated intermittent exposures, we evaluated objective performance on a computerized visual divided attention test in chronically unhealthy Gulf War veterans (n = 22 ill with low-level chemical intolerance (CI); n = 24 ill without CI), healthy Gulf War veterans (n = 23), and healthy Gulf War era veterans (n = 20). Testing was done before and after each of three weekly, double blind, low-level JP-8 jet fuel or clean air sham exposure laboratory sessions, including acoustic startle stimuli. RESULTS Unhealthy veterans receiving jet fuel had faster mean peripheral reaction times over sessions compared with unhealthy veterans receiving sham clean air exposures. Unhealthy Gulf veterans with CI exhibited faster post- vs. pre-session mean central reaction times compared with unhealthy Gulf veterans without CI. Findings were controlled for psychological distress variables. DISCUSSION These data on unhealthy Gulf veterans show an acceleration of divided attention task performance over the course of repeated low-level JP-8 exposures. The present faster reaction times are consistent with rat neurobehavioral studies on environmental toxicant cross-sensitization and nonlinear dose-response patterns with stimulant drugs, as well as some previous civilian studies using other exposure agents. Together with previous research findings, the data suggest involvement of central nervous system dopaminergic pathways in affected Gulf veterans.

[1]  Ying Zhang,et al.  The Influence of Stimulants, Sedatives, and Fatigue on Tunnel Vision: Risk Factors for Driving and Piloting , 2001, Hum. Factors.

[2]  T L Kurt,et al.  Self-reported exposure to neurotoxic chemical combinations in the Gulf War. A cross-sectional epidemiologic study. , 1997, JAMA.

[3]  J. DeLuca,et al.  Cognitive Functioning in Gulf War Illness , 2001, Journal of clinical and experimental neuropsychology.

[4]  G. Schwartz,et al.  Self-reported chemical sensitivity and wartime chemical exposures in Gulf War veterans with and without decreased global health ratings. , 1998, Military medicine.

[5]  K. Fuxe,et al.  Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat. , 1993, Toxicology.

[6]  Han K. Kang,et al.  Gulf War Veterans' Health: Medical Evaluation of a U.S. Cohort , 2005, Annals of Internal Medicine.

[7]  Kane Rl,et al.  Neuropsychological and psychological functioning in chronic fatigue syndrome. , 1997, Neuropsychiatry, neuropsychology, and behavioral neurology.

[8]  D. Clauw,et al.  The relationship between fibromyalgia and the multiple chemical sensitivity syndrome. , 1997, Scandinavian journal of rheumatology.

[9]  J. Grafman,et al.  Divided Attention Deficits in Patients With Chronic Fatigue Syndrome , 2001, Applied neuropsychology.

[10]  Thomas J. Prihoda,et al.  The Environmental Exposure and Sensitivity Inventory (EESI): a standardized approach for measuring chemical intolerances for research and clinical applications , 1999, Toxicology and industrial health.

[11]  H. Fowler,et al.  Oscellatory-sensitization model of repeated drug exposure: Cocaine's effects on shock-induced hypoalgesia , 1998, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[12]  B. Sorg.  Mesocorticolimbic Dopamine Systems: Cross‐Sensitization between Stress and Cocaine , 1992, Annals of the New York Academy of Sciences.

[13]  T L Kurt,et al.  Evaluation of neurologic function in Gulf War veterans. A blinded case-control study. , 1997, JAMA.

[14]  S. Antelman,et al.  Oscillation follows drug sensitization: implications. , 1996, Critical reviews in neurobiology.

[15]  R. Haley,et al.  Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels. , 2000, Archives of neurology.

[16]  A. Shetty,et al.  Stress and Combined Exposure to Low Doses of Pyridostigmine Bromide, DEET, and Permethrin Produce Neurochemical and Neuropathological Alterations in Cerebral Cortex, Hippocampus, and Cerebellum , 2004, Journal of toxicology and environmental health. Part A.

[17]  T. Prihoda,et al.  A controlled comparison of symptoms and chemical intolerances reported by Gulf War veterans, implant recipients and persons with multiple chemical sensitivity , 1999, Toxicology and industrial health.

[18]  B. Uttl,et al.  North American Adult Reading Test: Age Norms, Reliability, and Validity , 2002, Journal of clinical and experimental neuropsychology.

[19]  D. Nyenhuis,et al.  Adult and geriatric normative data and validation of the profile of mood states. , 1999, Journal of clinical psychology.

[20]  R. Bootzin,et al.  Differing Patterns of Cognitive Dysfunction and Heart Rate Reactivity in Chemically-Intolerant Individuals With and Without Lifestyle Changes , 1999 .

[21]  Robert L. Carpenter,et al.  EFFECTS OF REPEATED EXPOSURE OF RATS TO JP-5 OR JP-8 JET FUEL VAPOR ON NEUROBEHAVIORAL CAPACITY AND NEUROTRANSMITTER LEVELS , 2001, Journal of toxicology and environmental health. Part A.

[22]  J. M. Peterson,et al.  Self-reported illness from chemical odors in young adults without clinical syndromes or occupational exposures. , 1993, Archives of environmental health.

[23]  B. Axelrod,et al.  Neuropsychological findings in a sample of Operation Desert Storm veterans. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[24]  T. G. Randolph.  Specific adaptation. , 1978, Annals of allergy.

[25]  W. Anger,et al.  Neurobehavioral deficits associated with chronic fatigue syndrome in veterans with Gulf War unexplained illnesses , 2001, Journal of the International Neuropsychological Society.

[26]  Neil B. Rappaport,et al.  A daily stress inventory: Development, reliability, and validity , 1987, Journal of Behavioral Medicine.

[27]  B. Ferger,et al.  Effects of cocaine on the EEG power spectrum of rats are significantly altered after its repeated administration: do they reflect sensitization phenomena? , 1996, Naunyn-Schmiedeberg's Archives of Pharmacology.

[28]  David Edwards,et al.  One experience with ‘lower’ or ‘higher’ intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability , 1991, Brain Research.

[29]  G. Schwartz,et al.  Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: support for a neural sensitization model. , 1998, Journal of women's health.

[30]  S. Swindell,et al.  Repeated Formaldehyde Effects in an Animal Model for Multiple Chemical Sensitivity , 2001, Annals of the New York Academy of Sciences.

[31]  P. Kalivas,et al.  Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies , 2000, Psychopharmacology.

[32]  Henry A. Nasrallah,et al.  Hippocampal dysfunction in Gulf War Syndrome. A proton MR spectroscopy study , 2004, Brain Research.

[33]  Carol A. Barnes,et al.  Effects of Aerosol-Vapor JP-8 Jet Fuel on the Functional Observational Battery, and Learning and Memory in the Rat , 2001, Archives of environmental health.

[34]  J. M. Peterson,et al.  Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population. , 1993, Archives of environmental health.

[35]  Gleb P. Tolstykh,et al.  Cognitive performance and cerebrohemodynamics associated with the Persian Gulf Syndrome , 2001, Toxicology and industrial health.

[36]  R. Haley,et al.  Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. , 1999, Toxicology and applied pharmacology.

[37]  G. G. Brown,et al.  Gulf War veterans: a neuropsychological examination. , 1997, Journal of clinical and experimental neuropsychology.

[38]  John B. Nezlek,et al.  Multilevel Random Coefficient Analyses of Event- and Interval-Contingent Data in Social and Personality Psychology Research , 2001 .

[39]  Robert L. Carpenter,et al.  EFFECTS OF REPEATED EXPOSURE TO JP-8 JET FUEL VAPOR ON LEARNING OF SIMPLE AND DIFFICULT OPERANT TASKS BY RATS , 2001, Journal of toxicology and environmental health. Part A.

[40]  C. Drake,et al.  Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness , 2000, Physiology & Behavior.

[41]  B. Doebbeling,et al.  Multiple chemical sensitivity syndrome: symptom prevalence and risk factors in a military population. , 2000, Archives of internal medicine.

[42]  P. Kalivas,et al.  The role of the nucleus accumbens in sensitization to drugs of abuse , 1992, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[43]  J. DeLuca,et al.  Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity. , 1998, Journal of medicine.

[44]  J. DeLuca,et al.  A Controlled Comparison of Multiple Chemical Sensitivities and Chronic Fatigue Syndrome , 1996, Psychosomatic medicine.

[45]  G. Schwartz,et al.  Concomitant Environmental Chemical Intolerance Modifies the Neurobehavioral Presentation of Women with Fibromyalgia , 2001 .

[46]  Trevor W. Robbins,et al.  Enhanced and Impaired Attentional Performance After Infusion of D1 Dopaminergic Receptor Agents into Rat Prefrontal Cortex , 2000, The Journal of Neuroscience.

[47]  G. Schwartz,et al.  VALIDATION OF A BRIEF SCREENING MEASURE OF ENVIRONMENTAL CHEMICAL SENSITIVITY: THE CHEMICAL ODOR INTOLERANCE INDEX , 1997 .

[48]  Han K. Kang,et al.  Mortality among U.S. veterans of the Persian Gulf War. , 1996, The New England journal of medicine.

[49]  B. Ferger,et al.  Sensitization to d-amphetamine after its repeated administration: evidence in EEG and behaviour , 1997, Naunyn-Schmiedeberg's Archives of Pharmacology.

[50]  A. Palmer,et al.  The Effects of Ethanol on Striatal Dopamine and Frontal Cortical D-[3H]Aspartate Efflux Oscillate with Repeated Treatment , 1996, Neuropsychopharmacology.

[51]  W. Reeves,et al.  Chronic multisymptom illness affecting Air Force veterans of the Gulf War. , 1998, JAMA.

[52]  G. Schwartz,et al.  EEG sensitization during chemical exposure in women with and without chemical sensitivity of unknown etiology , 1999, Toxicology and industrial health.

[53]  Han K. Kang,et al.  Post-traumatic stress disorder and chronic fatigue syndrome-like illness among Gulf War veterans: a population-based survey of 30,000 veterans. , 2003, American journal of epidemiology.

[54]  R. Bootzin,et al.  Slowed reaction time performance on a divided attention task in elderly with environmental chemical odor intolerance. , 1996, The International journal of neuroscience.

[55]  H. Westberg,et al.  Repeated Low-Level Formaldehyde Exposure Produces Cross-Sensitization to Cocaine: Possible Relevance to Chemical Sensitivity in Humans , 1998, Neuropsychopharmacology.

[56]  D. Bourdette,et al.  Symptom Factor Analysis, Clinical Findings, and Functional Status in a Population-Based Case Control Study of Gulf WarUnexplained Illness , 2001, Journal of occupational and environmental medicine.

[57]  L. Murri,et al.  Effects of prolonged wakefulness combined with alcohol and hands‐free cell phone divided attention tasks on simulated driving , 2005, Human psychopharmacology.

[58]  I. Bell,et al.  Polysymptomatic syndromes and autonomic reactivity to nonfood stressors in individuals with self-reported adverse food reactions. , 1993, Journal of the American College of Nutrition.

[59]  M. Tschirgi,et al.  Exposure to repeated low-level formaldehyde in rats increases basal corticosterone levels and enhances the corticosterone response to subsequent formaldehyde , 2001, Brain Research.

[60]  B. Natelson,et al.  Impaired associative learning in chronic fatigue syndrome , 1998, Neuroreport.

[61]  Christopher Drake,et al.  Ethanol and sleep loss: a "dose" comparison of impairing effects. , 2003, Sleep.

[62]  J. M. Peterson,et al.  Neuropsychiatric and somatic characteristics of young adults with and without self-reported chemical odor intolerance and chemical sensitivity. , 1996, Archives of environmental health.

[63]  P. Brantley,et al.  Convergence between the Daily Stress Inventory and endocrine measures of stress. , 1988, Journal of consulting and clinical psychology.

[64]  M. Lezak.  Neuropsychological assessment, 3rd ed. , 1995 .

[65]  S. Antelman.  Time-Dependent Sensitization in Animals: A Possible Model of Multiple Chemical Sensitivity in Humans , 1994, Toxicology and industrial health.

[66]  B. Doebbeling,et al.  Quality of life and health-services utilization in a population-based sample of military personnel reporting multiple chemical sensitivities. , 1999, Journal of occupational and environmental medicine.

[67]  Susan K. Johnson,et al.  Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[68]  P. Lioy,et al.  Responses to Controlled Diesel Vapor Exposure Among Chemically Sensitive Gulf War Veterans , 2004, Psychosomatic medicine.

[69]  J. Coull.  Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology , 1998, Progress in Neurobiology.

[70]  W. Sturm,et al.  Neuropsychological assessment , 2007, Journal of Neurology.

[71]  H. Ursin,et al.  Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls. , 2003, Journal of affective disorders.