Chronic Fatigue Syndrome: New Jersey

Janal MN, Ciccone DS, Natelson BH. · Fatigue Research Center and Department of Psychiatry, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA. · Biol Psychol. · Pubmed #16473456 No free full text.

Abstract: The diagnosis of chronic fatigue syndrome (CFS), an illness characterized by medically unexplained fatigue, depends on a clinical case definition representing one or more pathophysiological mechanisms. To prepare for studies of these mechanisms, this study sought to identify subtypes of CFS. In 161 women meeting 1994 criteria for CFS, principal components analysis of the 10 'minor' symptoms of CFS produced three factors interpreted to indicate musculoskeletal, infectious and neurological subtypes. Extreme scores on one or more of these factors characterized about 2/3 of the sample. Those characterized by the neurological factor were at increased risk of reduced scores on cognitive tests requiring attention, working memory, long-term memory or rapid performance. In addition, the neurological subtype was associated with reduced levels of function. Those characterized by the musculoskeletal factor were at increased risk for the diagnosis of fibromyalgia (chronic widespread pain and mechanical allodynia) and reduced physical function. Those characterized by the infectious factor were less likely to evidence co-occurring fibromyalgia, and showed lesser risk of functional impairment. The prevalence of disability was increased in those with the highest scores on any of the subtypes, as well as in those with high scores on multiple factors. Depression and anxiety, while frequently present, were not more prevalent in any particular subtype, and did not increase with the severity of specific symptom reports. Results suggest that subtypes of CFS may be identified from reports of the minor diagnostic symptoms, and that these subtypes demonstrate construct validity.

Sigal LH, Hassett AL. · Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. · Int J Epidemiol. · Pubmed #16143662 links to  free full text

This publication has no abstract.

Natelson BH, Weaver SA, Tseng CL, Ottenweller JE. · CFS Cooperative Research Center and Department of Neurosciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA. · Clin Diagn Lab Immunol. · Pubmed #15642984 links to  free full text

Abstract: Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls. Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having comorbid depression than those with normal fluid. In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls. The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.

Yoshiuchi K, Quigley KS, Ohashi K, Yamamoto Y, Natelson BH. · Department of Neurosciences, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, East Orange, NJ 07018, USA. · Auton Neurosci. · Pubmed #15296795 No free full text.

Abstract: Although a number of studies have reported alterations in cardiac autonomic nervous system function in chronic fatigue syndrome (CFS), the results are not consistent across studies. Reasons for these discrepancies include (1) the use of a heterogeneous patient sample that included those with orthostatic postural tachycardia (POTS), a condition with an autonomic changes, and (2) the use of frequency domain techniques which require a stationary signal and averaging data across relatively long epochs. To deal with these shortcomings, we used the smoothed pseudo-Wigner-Ville transform (SPWVT) to analyze heart rate variability (HRV) and blood pressure variability (BPV) during head-up tilt (HUT) by separating CFS patients into those with and without POTS. SPWVT has the advantage of providing instantaneous information about autonomic function under nonstable physiological conditions. We studied 18 CFS patients without POTS, eight CFS patients with POTS and 25 sedentary healthy controls during supine rest and during the first 10 min after HUT. While we found significant effects of postural change in both groups for all autonomic variables, there were significant group x time interactions between CFS without POTS and controls for only instant center frequency (ICF) within the low frequency region both from HRV (p=0.02) and from BPV (p=0.01). Although the physiological meaning of ICF still remains unknown, the data suggest that even CFS patients without POTS may have a subtle underlying disturbance in autonomic function.

Busichio K, Tiersky LA, Deluca J, Natelson BH. · Chronic Fatigue Syndrome Center, Newark, New Jersey 07666, USA. · J Int Neuropsychol Soc. · Pubmed #15012848 No free full text.

Abstract: The degree of neuropsychological dysfunction across multiple domains was examined in individuals suffering from chronic fatigue syndrome (CFS). In this descriptive study, a similar series of neuropsychological tests was administered to a group of CFS patients and healthy participants. More specifically, CFS patients (n = 141) who met the 1994 Case Definition criteria were compared to 76 healthy control participants on tests of memory, attention (concentration), speed of information processing, motor speed, and executive functioning. On the 18 measures administered, CFS patients scored 1 standard deviation below the healthy mean on nine measures and scored 2 standard deviations below the healthy mean on four of the measures. Moreover, results indicated that CFS patients were more likely than healthy controls to fail (1.6 SD below the healthy mean) at least one test in each of the following domains: attention, speed of information processing, and motor speed, but not on measures of memory and executive functioning. Finally, CFS patients demonstrated a greater total number of tests failed across domains.

Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. · Chronic Fatigue Syndrome Cooperative Research Center, New Jersey Medical School, Newark, New Jersey 07018, USA. · J Rheumatol. · Pubmed #14760810 No free full text.

Abstract: OBJECTIVE: To examine the function of the nociceptive system in patients with fibromyalgia (FM) using functional magnetic resonance imaging (fMRI). METHODS: Two groups of women, 9 with FM and 9 pain-free, volunteered to participate. In Experiment 1, we assessed psychophysical responses to painful stimuli and prepared participants for fMRI testing. For Experiment 2, subjects underwent fMRI scanning while receiving painful and nonpainful heat stimuli. Conventional and functional MR images were acquired using a 1.5 T MR scanner. Scanning occurred over 5 conditions. Condition 1 served as a practice session (no stimuli). Conditions 2 and 5 consisted of nonpainful warm stimuli. Conditions 3 and 4 consisted of an absolute thermal pain stimulus (47 degrees C) and a perceptually equivalent pain stimulus delivered in counterbalanced order. RESULTS: Experiment 1 indicated that subjects with FM were significantly more sensitive to experimental heat pain than controls (p < 0.001). In Experiment 2, fMRI data indicated that the FM group exhibited greater activity than controls over multiple brain regions in response to both nonpainful and painful stimuli (p < 0.01). Specifically, in response to nonpainful warm stimuli, FM subjects had significantly greater activity than controls in prefrontal, supplemental motor, insular, and anterior cingulate cortices (p < 0.01). In response to painful stimuli, FM subjects had greater activity in the contralateral insular cortex (p < 0.01). Data from the practice session indicated brain activity in pain-relevant areas for the FM group but not for controls. CONCLUSION: Our results provide further evidence for a physiological explanation for FM pain.

Deluca J, Christodoulou C, Diamond BJ, Rosenstein ED, Kramer N, Natelson BH. · Department of Physical Medicine and Rehabilitation, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, USA. · J Int Neuropsychol Soc. · Pubmed #14751012 No free full text.

Abstract: To examine the relative influence of speed of information processing versus working memory ability, CFS participants with psychiatric comorbidity (CFS-Psych) and CFS without a psychiatric history (CFS-noPsych) were examined on tests of visual and auditory processing speed and visual and auditory working memory. Compared to healthy controls (HC) and a group of participants with rheumatoid arthritis (RA), the CFS-noPsych group displayed significantly reduced performance on tests of information processing speed, but not on tests of working memory. No significant differences were observed between the CFS-Psych group and any other group in the study. The implications of group heterogeneity on the understanding of cognitive impairment in CFS are discussed.

Peckerman A, Dahl K, Chemitiganti R, LaManca JJ, Ottenweller JE, Natelson BH. · VA Medical Center, East Orange, NJ 07018, USA. · Auton Neurosci. · Pubmed #14614966 No free full text.

Abstract: Abnormal cardiovascular stress responses have been reported in Gulf War veterans with chronic fatigue. However, many of these veterans also suffer from posttraumatic stress disorder (PTSD), which could potentially explain the reported abnormalities. To test this hypothesis, 55 Gulf veterans (GVs) with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) were stratified into groups with (N=16) and without (N=39) comorbid PTSD, and were compared to healthy Gulf veterans (N=47) on cardiovascular responses to a series of stressors. The CFS/ICF with PTSD group had lower blood pressure responses to speech and arithmetic tasks, and more precipitous declines and slower recoveries in blood pressure after standing up than the controls. Similar trends in the CF/ICF group without PTSD were not significant, however. Both CFS/ICF groups had blunted increases in peripheral vascular resistance during mental tasks. However, only the veterans with comorbid PTSD had diminished cardiac output responses to the mental stressors and excessive vasodilatory responses to standing. Symptoms of posttraumatic stress were significant predictors of hypotensive postural responses, but only in veterans reporting a significant exposure to wartime stress. We conclude that comorbid PTSD contributes to dysregulation of cardiovascular responses to mental and postural stressors in Gulf veterans with medically unexplained fatiguing illness, and may provide a physiological basis for increased somatic complaints in Gulf veterans with symptoms of posttraumatic stress.

Nagelkirk PR, Cook DB, Peckerman A, Kesil W, Sakowski T, Natelson BH, LaManca JJ. · Center for the Study of War-Related Illnesses, Veterans Affairs New Jersey Health Care, East Orange, NJ, USA. · Mil Med. · Pubmed #14529252 No free full text.

Abstract: A large overlap exists between the diagnosis of chronic fatigue syndrome (CFS) and the unexplained symptoms reported by many Gulf War veterans (GV). Previous investigations have reported reduced aerobic capacity in civilians with CFS. The present investigation examined metabolic responses to maximal exercise in GVs with CFS compared with healthy GVs. Cardiorespiratory and metabolic responses were recorded during a maximal exercise test on a cycle ergometer. The groups were not different in any demographic category (p > 0.05) or self-reported physical activity (p > 0.05). No differences were observed between groups for maximal oxygen uptake (28.9 +/- 6.7 mL/kg/min for CFS vs. 30.8 +/- 7.1 mL/kg/min for controls; p = 0.39), heart rate (155.8 +/- 16.1 bpm for CFS vs. 163.3 +/- 14.9 bpm for controls; p = 0.17), exercise time (9.6 +/- 1.5 minutes for CFS vs. 10.2 +/- 1.4 minutes for controls; p = 0.26), or workload achieved (208 +/- 36.7 W for CFS vs. 224 +/- 42.9 W for controls; p = 0.25). Likewise, no differences were observed at submaximal intensities (p > 0.05). Compared with healthy controls, GVs who report multiple medically unexplained symptoms and meet criteria for CFS do not show a decreased exercise capacity. Thus, it does not appear that the pathology of the GVs with CFS includes a deficiency with mobilizing the cardiopulmonary system for strenuous physical effort.

Peckerman A, LaManca JJ, Qureishi B, Dahl KA, Golfetti R, Yamamoto Y, Natelson BH. · VA Medical Center, War-Related Illness and Injury Study Center, East Orange, New Jersey 07018, USA. · Psychosom Med. · Pubmed #14508037 links to  free full text

Abstract: OBJECTIVE: Altered cardiovascular responses to mental and postural stressors have been reported in chronic fatigue syndrome (CFS). This study examined whether those findings may involve changes in baroreceptor reflex functioning. METHODS: Chronotropic baroreceptor reflex (by sequential analysis) and cardiovascular stress responses were recorded during postural (5-minute of active standing) and cognitive (speech task) stress testing in patients with CFS grouped into cases with severe (N = 21) or less severe (N = 22) illness, and in 29 matched control subjects. RESULTS: Patients with CFS had a greater decline in baroreceptor reflex sensitivity (BRS) during standing, although only those with severe CFS were significantly different from the controls. Systolic blood pressure declined during standing in the control group but was maintained in the CFS patients. In contrast, the patients with less severe CFS had blunted increases in blood pressure during the speech task, which could not, however, be explained by inadequate inhibition of the baroreceptor reflex, with all groups showing an appropriate reduction in BRS during the task. CONCLUSIONS: These results indicate that in CFS, deficiencies in orthostatic regulation, but not in centrally mediated stress responses, may involve the baroreceptor reflex. This study also suggests that classifying patients with CFS on illness severity may discriminate between patients with abnormalities in peripheral vs. central mechanisms of cardiovascular stress responses.

Peckerman A, LaManca JJ, Dahl KA, Chemitiganti R, Qureishi B, Natelson BH. · Department of Neurosciences, CFS Cooperative Research Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA. · Am J Med Sci. · Pubmed #12920435 No free full text.

Abstract: BACKGROUND: Findings indicative of a problem with circulation have been reported in patients with chronic fatigue syndrome (CFS). We examined this possibility by measuring the patient's cardiac output and assessing its relation to presenting symptoms. METHODS: Impedance cardiography and symptom data were collected from 38 patients with CFS grouped into cases with severe (n = 18) and less severe (n = 20) illness and compared with those from 27 matched, sedentary control subjects. RESULTS: The patients with severe CFS had significantly lower stroke volume and cardiac output than the controls and less ill patients. Postexertional fatigue and flu-like symptoms of infection differentiated the patients with severe CFS from those with less severe CFS (88.5% concordance) and were predictive (R2 = 0.46, P < 0.0002) of lower cardiac output. In contrast, neuropsychiatric symptoms showed no specific association with cardiac output. CONCLUSIONS: These results provide a preliminary indication of reduced circulation in patients with severe CFS. Further research is needed to confirm this finding and to define its clinical implications and pathogenetic mechanisms.

Chiaravalloti ND, Christodoulou C, Demaree HA, DeLuca J. · Kessler Medical Rehabilitation Research and Education Corporation, West Orange, NJ 07052, USA. · J Clin Exp Neuropsychol. · Pubmed #12911103 No free full text.

Abstract: The current study was designed to examine how the construct of human information processing speed is conceptualized and measured, while also examining the influence of information processing speed on higher cognitive processes (i.e., learning). A mixed medical sample of 92 subjects participated in this study. Subjects underwent a broad-based neuropsychological evaluation, including measures of verbal and visuospatial new learning, spatial and verbal working memory, simple reaction time, choice reaction time, and information processing speed. Principal components factor analysis with varimax rotation resulted in a three-factor solution, comprised of: (1) simple speed/reaction time, (2) complex information processing and new learning, and (3) working memory. Notably, this factor solution identified 2 distinct forms of processing speed--simple and complex information processing speeds. In contrast to the abundance of literature grouping these two constructs together under one term (i.e., processing speed), these results indicate simple and complex speed to be distinct constructs assessed with different neuropsychological instruments. While the expected relationship between complex information processing capacities and working memory abilities was evident in this study, information processing speed also showed a significant relationship with new learning ability. The implications of this intriguing relationship are discussed.

Tiersky LA, Matheis RJ, Deluca J, Lange G, Natelson BH. · Fairleigh Dickinson University, School of Psychology, Williams Hall (T-WH1-01), 1000 River Road, Teaneck, NJ 07666, USA. · J Nerv Ment Dis. · Pubmed #12819552 No free full text.

Abstract: Individuals with chronic fatigue syndrome (CFS) face chronic physical debilitation, reduced neuropsychological functioning, and changes in emotional well-being that significantly detract from quality of life. The role of psychiatric disturbance in reducing quality of life in CFS remains unclear. In the current investigation, the role of psychiatric status in reducing health-related quality of life in CFS was examined. Four subject groups were compared on measures of functional well-being, mood, and neuropsychological status: individuals with CFS and no history of psychiatric illness, individuals who had current symptoms of psychiatric illness that began after their CFS diagnosis, individuals who had current symptoms of psychiatric illness that began before their CFS diagnosis, and a healthy sedentary control group. Overall, it was found that individuals with CFS suffer from profound physical impairment. Concurrent psychiatric illness, however, did not adversely affect physical functional capacity. Physical functional capacity was not worse in individuals with a concurrent psychiatric illness. As expected, concurrent psychiatric illness was found to reduce emotional well-being. Moreover, individuals with a psychiatric illness that predated the onset of CFS suffered the greatest emotional distress. Thus, an individual's psychiatric history should be considered when attempting to understand the factors maintaining disability in CFS.

Ciccone DS, Busichio K, Vickroy M, Natelson BH. · Department of Psychiatry, UMDNJ-New Jersey Medical School, Newark, NJ 07107, USA. · J Psychosom Res. · Pubmed #12726901 No free full text.

Abstract: OBJECTIVE: The long-term consequences of chronic fatigue syndrome (CFS) include substantial impairment in physical functioning and high levels of work disability. In the absence of a medical explanation for this impairment, some have speculated that it may be due to comorbid psychiatric illness or personality disorder. We addressed this possibility by comparing the functional status of three CFS groups: no psychiatric diagnosis, psychiatric illness only, psychiatric illness and personality disorder. A second aim of the study was to determine whether a continuous measure of psychological distress could provide a better account of impairment than psychiatric diagnosis. METHOD: The study sample consisted of 84 consecutive female referrals with CFS. All participants satisfied the case definition and completed an assessment protocol consisting of: physical examination, psychiatric interview and self-report questionnaires. RESULTS: Psychiatric illness, either alone or in combination with a comorbid personality disorder, was not associated with physical impairment or disability in female participants. A regression model of physical functioning found that psychological distress accounted for 6% and symptom severity for 41% of the variance (P=.06 and <.01, respectively). In the case of disability, the corresponding percentages were 2% and 18% (NS and P<.01, respectively). The modest effects of psychological distress could not be attributed to symptom severity. CONCLUSIONS: Although psychiatric illness and personality disorder was prevalent, neither could explain the effects of CFS on physical functioning and disability. As yet, there is no psychological or medical explanation for the behavioral consequences of CFS.

Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. · Center for the Study of War-Related Illnesses, VA NJ Health Care, East Orange, NJ 07018, USA. · Med Sci Sports Exerc. · Pubmed #12673138 No free full text.

Abstract: PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). We have challenged this notion by examining perceived exertion in civilian females with CFS and expressing the data relative to exercise capacity (%[OV0312]O(2max)). The purpose of the present investigation was to further examine RPE during exercise in a unique population of CFS patients, Gulf veterans (GV). METHODS: Thirty-four GV (N = 15 CFS, 42 +/- 8 yr; N = 19 healthy, 43 +/- 5 yr) performed a maximal exercise test on a cycle ergometer. After a 3-min warm-up, exercise intensity increased by 30 W every minute until exhaustion. RPE were obtained during the last 15 s of each minute using Borg's CR-10 scale. RESULTS: With the exception of peak [OV0312]E, there were no significant differences in any peak exercise variables. Repeated measures ANOVA revealed significantly higher RPE at each power output examined (F(1,32) = 16.4, P < 0.001). Group differences in RPE remained significant when analyzed relative to peak [OV0312]O(2) (F(1,32) = 7.2, P = 0.01). Both group main effects and the interaction were eliminated when self-reported fatigue symptoms were controlled for in the analyses. Power functions for RPE as a function of relative oxygen consumption were not different between groups and were significantly greater than a linear value of 1.0 (1.6 +/- 0.3 for both groups, P < 0.02). CONCLUSIONS: Our results show that RPE are greater in GV with CFS regardless of whether the data were expressed in terms of absolute or relative exercise intensity. However, self-reported fatigue associated with CFS eliminated the group differences. These results suggest that GV with CFS were unique compared with their civilian counterparts. Future research aimed at determining the influence of preexisting fatigue on RPE during exercise is warranted.

Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Lamanca JJ, Natelson BH. · Center for the Study of War-Related Illnesses, VA NJ Health Care, East Orange, NJ 07018, USA. · Med Sci Sports Exerc. · Pubmed #12673137 No free full text.

Abstract: PURPOSE: It has been reported that ratings of perceived exertion (RPE) are elevated in chronic fatigue syndrome (CFS). However, methodological limitations have rendered this conclusion suspect. The purpose of the present investigation was to examine RPE during exercise in civilians with CFS by comparing subjects at both absolute exercise stage and relative oxygen consumption reference criteria. METHODS: A sample of 39 civilian females (N = 19 CFS, 34 +/- 7 yr; N = 20 healthy controls, 33 +/- 7 yr) underwent a maximal exercise test on a treadmill. RPE were obtained during the last 15 s of each 3-min stage using Borg's 6-20 scale. RESULTS: There were no significant differences in peak [OV0312]O(2), RER, or RPE. However, controls exercised longer (20.0 +/- 1.1 vs 15.9 +/- 1.1 min, P = 0.01, healthy vs CFS) and had higher peak HR (183 +/- 3 vs 174 +/- 2 bpm, P = 0.03, healthy vs CFS). Civilians with CFS reported higher RPE at stages 3 through 5 compared with controls (F(3,111)= 3.6,P = 0.017). Preexercise fatigue ratings were not a significant predictor of perceived exertion during exercise. There were no group differences (F(1,37)= 1.9, P = 0.17) when RPE were expressed relative to peak [OV0312]O(2). CONCLUSIONS: Our results show that RPE are greater in civilians with CFS when the data are expressed in terms of absolute exercise intensity. However, by examining RPE relative to a common maximum (i.e., peak [OV0312]O(2)) no differences were observed. The findings of the present investigation challenge the notion that RPE are dysregulated in CFS.

Ciccone DS, Natelson BH. · Department of Psychiatry, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA. · Psychosom Med. · Pubmed #12651994 links to  free full text

Abstract: OBJECTIVE: Evidence of comorbidity among unexplained illness syndromes raises the possibility that all are variants of a single functional disorder, leading some to suggest that separate case definitions for chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivity (MCS) may be unnecessary. Our objective was to determine whether discrete diagnostic labels provide useful information about physical functioning, symptom severity, and risk of psychiatric illness. METHODS: The sample consisted of 163 consecutive female referrals with CFS enrolled at a tertiary clinic. Each participant was retrospectively assigned to one of four groups: CFS only, CFS/FM, CFS/MCS, and CFS/FM/MCS. At enrollment, participants gave their history, underwent a physical examination and a standardized psychiatric interview (Diagnostic Interview Schedule), and answered self-report questionnaires. RESULTS: Additional unexplained syndromes were prevalent: 37% met criteria for FM, and 33% met criteria for MCS. With the exception of FM-related pain and disability, there were few differences between the CFS only and CFS with comorbid illness groups. Patients with additional illness were more likely to have major depression and a higher risk of psychiatric morbidity compared with patients in the CFS only group (p <.01). Rates of lifetime depression increased from 27.4% in the CFS only group to 52.3% in the CFS/FM group, 45.2% in the CFS/MCS group, and 69.2% in the CFS/FM/MCS group. CONCLUSIONS: The prevalence of comorbid illness in the present CFS sample and the failure to find widespread differences in symptom severity can be seen as support for the single syndrome hypothesis. On the other hand, the existence of discrete syndromes could not be ruled out because of reliable differences between CFS and CFS/FM. Increasing comorbidity was associated with a corresponding increase in risk of major depression.

Yamamoto Y, LaManca JJ, Natelson BH. · Department of Neurosciences, New Jersey Medical School, East Orange, New Jersey 07018-1095, USA. · Exp Biol Med (Maywood). · Pubmed #12563023 links to  free full text

Abstract: The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70 degrees HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SD(RRI)) of RR intervals (RRI), amplitudes of low- (A(LF); 0.04-0.15 Hz) and high-frequency (A(HF); >0.15 Hz) harmonic as well as aperiodic, fractal (A(FR); 1/f(beta)) spectral components, the spectral exponent beta, and the difference in these values between baseline and HUT for each subject. In the supine baseline, only mean RRI was significantly (P < 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SD(RRI) (P < 0.01), A(HF) (P < 0.05), and A(FR) (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for A(FR) (deltaA(FR)) was significantly (P < 0.01) lower in CFS than in CON, suggesting that A(FR)is a disease-specific response of HRV to HUT. When a cut-off level was set to deltaA(FR) = -2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.

Brimacombe M, Zhang Q, Lange G, Natelson BH. · Department of Preventive Medicine, University of Medicine and Dentistry - New Jersey Medical School, Newark, NJ 070718, USA. · Neuroimmunomodulation. · Pubmed #12372983 No free full text.

Abstract: We explored the relationship between a set of immunological variables and a set of cognitive and functional status measures and a diagnosis of chronic fatigue syndrome (CFS) in civilians and veterans using various regression and factor analytic methods. Our approach emphasized the extraction of a few distinct factors in order to limit statistical problems associated with doing large numbers of multiple comparisons. This approach led to our finding cytokine data grouping into type 1 and type 2 clusters. A type 2 cluster plus a T and B cell factor predicted CFS caseness for Gulf War veterans but not for civilians with CFS. When a cognitive variable, reaction time, was added into the model, both immunological factors lost statistical significance; this indicates that the cognitive variable reaction time moderated the effects of the immunological factors in predicting patient status. We did a similar analysis on the roles of the immunological and cognitive variables in functional status using SF-36 data. Higher levels of these same two immunological factors predicted poorer general health as well as poorer physical and social functioning in Gulf War veterans but not in civilians with CFS. When the reaction time factor was added, only the lymphocyte factor remained significant. This implies that lymphocytes are directly related to functional status in Gulf War veterans with CFS, but the Th2 factor produces its effect on functional status via changes in cognitive abilities.

Nelson JJ, Natelson BH, Peckerman A, Pollet C, Lange G, Tiersky L, Servatius RJ, Policastro T, Fiedler N, Ottenweller JE. · Center for Environmental Hazards Research, Department of Veterans Affairs Medical Center, East Orange, NJ 07018, USA. · Mil Med. · Pubmed #11778414 No free full text.

Abstract: An important question for researchers interested in long-term consequences of military service is the health outcome of symptomatic Persian Gulf War Veterans. From an original group of 76 Gulf War Veterans who received the diagnosis of severe fatiguing illness, we attempted to get 58 veterans to return to our center for a second evaluation. Thirteen returned. Two had recovered by the time of revisit, but the rest remained ill; however, only one was so ill as to be unable to work. The data suggest that the medical consequences of serving in the Persian Gulf are not transient. The difficulty in getting veterans to return to our center suggests potential problems in the proposed nation-wide longitudinal health outcome study of Persian Gulf War Veterans.

LaManca JJ, Peckerman A, Sisto SA, DeLuca J, Cook S, Natelson BH. · Chronic Fatigue Syndrome Cooperative Research Center, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA. · Psychosom Med. · Pubmed #11573024 links to  free full text

Abstract: OBJECTIVE: The purpose of this study was to compare the cardiovascular responses of patients with chronic fatigue syndrome (CFS) to healthy control subjects when performing stressful cognitive tasks before and after strenuous exercise. METHOD: Beat-by-beat blood pressure and electrocardiogram were recorded on 19 women with CFS and 20 healthy nonexercising (ie, sedentary) women while they performed cognitive tests before, immediately after, and 24 hours after incremental exercise to exhaustion. RESULTS: Diminished heart rate (p <.01) and systolic (p <.01) and diastolic (p <.01) blood pressure responses to stressful cognitive testing were seen in patients with CFS when compared with healthy, sedentary controls. This diminished stress response was seen consistently in patients with CFS across three separate cognitive testing sessions. Also, significant negative correlations between self-ratings of CFS symptom severity and cardiovascular responses were seen (r = -0.62, p <.01). CONCLUSIONS: Women with CFS have a diminished cardiovascular response to cognitive stress; however, exercise did not magnify this effect. Also, the data showed that the patients with the lowest cardiovascular reactivity had the highest ratings of CFS symptom severity, which suggests that the individual response of the patient with CFS to stress plays a role in the common complaint of symptoms worsening after stress.

Gilhooly PE, Ottenweller JE, Lange G, Tiersky L, Natelson BH. · Veterans Administration, New Jersey Health Care System, 385 Tremont Avenue, East Orange, NJ 07018, USA. · J Sex Marital Ther. · Pubmed #11554210 No free full text.

Abstract: Chronic fatigue (CF) is one of the most common conditions reported by Gulf War veterans. This study evaluated female sexual dysfunction (FSD) in veterans with or without complaints of CF. Subjects were screened for medical and psychiatric causes of CF. They included 22 healthy subjects and 26 with fatiguing symptoms. FSD was reported by 10% of controls and by 60% of the fatigued (p < .002) while 19% versus 81% (p < .001) noted decreased libido. FSD was more prevalent in fatigued veterans than in the controls. This relationship was not mediated by an Axis I diagnosis. This appears to be the first report of sexual dysfunction in CF.

Tiersky LA, DeLuca J, Hill N, Dhar SK, Johnson SK, Lange G, Rappolt G, Natelson BH. · School of Psychology, Fairleigh Dickinson University, 1000 River Road, Mail Stop T-WH1-01, Teaneck, NJ 07666, USA. · Appl Neuropsychol. · Pubmed #11388123 No free full text.

Abstract: The longitudinal course of subjective and objective neuropsychological functioning, psychological functioning, disability level, and employment status in chronic fatigue syndrome (CFS) was examined. The relations among several key outcomes at follow-up, as well as the baseline characteristics that predict change (e.g., improvement), were also evaluated. The study sample consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Centers for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM = 1.7) months following their initial visit (range = 24-63 months). Results indicated that objective and subjective attention abilities, mood, level of fatigue, and disability improve over time in individuals with CFS. Moreover, improvements in these areas were found to be interrelated at follow-up. Finally, psychiatric status, age, and between-test duration were significant predictors of outcome. Overall, the prognosis for CFS appears to be poor, as the majority of participants remained functionally impaired over time and were unemployed at follow-up, despite the noted improvements.

Lange G, Holodny AI, DeLuca J, Lee HJ, Yan XH, Steffener J, Natelson BH. · Departments of Psychiatry and Radiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 30 Bergen Street, Newark, NJ 07107, USA. · Appl Neuropsychol. · Pubmed #11388120 No free full text.

Abstract: Previous qualitative volumetric assessment of lateral ventricular enlargement in chronic fatigue syndrome (CFS) has provided evidence for subtle structural changes in the brains of some individuals with CFS. The aim of this pilot study was to determine whether a more sensitive quantitative assessment of the lateral ventricular system would support the previous qualitative findings. In this study, we compared the total lateral ventricular volume, as well as the right and left hemisphere subcomponents in 28 participants with CFS and 15 controls. Ventricular volumes in the CFS group were larger than in control groups, a difference that approached statistical significance. Group differences in ventricular asymmetry were not observed. The results of this study provide further evidence of subtle pathophysiological changes in the brains of participants with CFS.

Natelson BH. · Fatigue Research Center, New Jersey Medical School, 88 Ross St, East Orange, NJ 07018. · JAMA. · Pubmed #11368714 No free full text.

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