Tag: Natelson

Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndromepatients with and without comorbid fibromyalgia

Abstract:

BACKGROUND: Some think chronic fatigue syndrome (CFS) and fibromyalgia (FM) are variants of the same illness process. This would imply that CFS patients with and without comorbid FM have similar biological underpinnings. To test this, we compared serotonergic-based responses, plasma prolactin (PRL), and self-reported measures of fatigue to intravenous infusion of tryptophan among patients with CFS alone, CFS + FM, and healthy controls.

METHODS: Men and women with CFS alone or CFS + FM and healthy subjects, none with current major depressive disorder (MDD), were given 120 mg of L-tryptophan per kg lean body mass intravenously (i.v.). Before and after tryptophan infusion, blood samples were collected, and plasma PRL, tryptophan, and kynurenine concentrations were determined.

RESULTS: Women with CFS alone, but not CFS + FM, showed upregulated plasma PRL responses compared with controls. There were no differences among groups of men. Plasma tryptophan and kynurenine concentrations did not differ among groups.

CONCLUSIONS: These results indicate that women with CFS alone have upregulated serotonergic tone that is not seen in those with comorbid FM. The lack of effect in men suggests a mechanism that might explain, in part, the increased prevalence of CFS in women. The data support the interpretation that CFS in women is a different illness from FM.

 

Source: Weaver SA, Janal MN, Aktan N, Ottenweller JE, Natelson BH. Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndrome patients with and without comorbid fibromyalgia. J Womens Health (Larchmt). 2010 May;19(5):951-8. doi: 10.1089/jwh.2009.1697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875960/ (Full article)

 

Cytokines across the night in chronic fatigue syndrome with and without fibromyalgia

Abstract:

The symptoms of chronic fatigue syndrome (CFS) are consistent with cytokine dysregulation. This has led to the hypothesis of immune dysregulation as the cause of this illness. To further test this hypothesis, we did repeated blood sampling for cytokines while patients and matched healthy controls slept in the sleep lab.

Because no one method for assaying cytokines is acknowledged to be better than another, we assayed for protein in serum, message in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs.

We found no evidence of proinflammatory cytokine upregulation. Instead, in line with some of our earlier studies, we did find some evidence to support a role for an increase in interleukin-10, an anti-inflammatory cytokine. Although the changes were small, they may contribute to the common complaint in CFS patients of disrupted sleep.

 

Source: Nakamura T, Schwander SK, Donnelly R, Ortega F, Togo F, Broderick G, Yamamoto Y, Cherniack NS, Rapoport D, Natelson BH. Cytokines across the night in chronic fatigue syndrome with and without fibromyalgia. Clin Vaccine Immunol. 2010 Apr;17(4):582-7. doi: 10.1128/CVI.00379-09. Epub 2010 Feb 24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849324/ (Full article)

 

Sleep is not disrupted by exercise in patients with chronic fatigue syndromes

Abstract:

PURPOSE: Patients with chronic fatigue syndrome (CFS) report that exertion produces dramatic symptom worsening. We hypothesized this might be due to the exacerbation of an underlying sleep disorder, which we have previously demonstrated to exist.

METHODS: Female patients with CFS and matched healthy controls with no evidence of major depressive disorder were studied with overnight polysomnography on a baseline night and on a night after their performance of a maximal exercise test.

RESULTS: CFS patients as a group had evidence for disturbed sleep compared with controls. Although exercise improved sleep for healthy subjects, it did not do this for the group as a whole. When we stratified the sample on the basis of self-reported sleepiness after a night’s sleep, the patient group with reduced morning sleepiness showed improvement in sleep structure, whereas those with increased morning sleepiness continued to show evidence for sleep disruption.

CONCLUSIONS: Sleep is disturbed in CFS patients as a group, but exercise does not exacerbate this sleep disturbance. Approximately half the patients studied actually sleep better after exercise. Therefore, activity-related symptom worsening is not caused by worsened sleep.

 

Source: Togo F, Natelson BH, Cherniack NS, Klapholz M, Rapoport DM, Cook DB. Sleep is not disrupted by exercise in patients with chronic fatigue syndromes. Med Sci Sports Exerc. 2010 Jan;42(1):16-22. doi: 10.1249/MSS.0b013e3181b11bc7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796587/ (Full article)

 

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia

Abstract:

INTRODUCTION: We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal.

METHODS: We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase.

RESULTS: CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night’s sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group.

CONCLUSION: CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before. This sleep disruption may explain the overwhelming fatigue, report of unrefreshing sleep, and pain in this subgroup of patients.

Comment in: How much sleep apnea is too much? [Arthritis Res Ther. 2009]

 

Source: Togo F, Natelson BH, Cherniack NS, FitzGibbons J, Garcon C, Rapoport DM. Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia. Arthritis Res Ther. 2008;10(3):R56. doi: 10.1186/ar2425. Epub 2008 May 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483445/ (Full article)

 

Chronic fatigue syndrome in male Gulf war veterans and civilians: a further test of the single syndrome hypothesis

Abstract:

Different modes of fatigue onset in male Gulf War veterans versus male civilians raise the possibility that chronic fatigue syndrome (CFS) may not be a single disease entity. We addressed this issue by comparing 45 male veterans with CFS to 84 male civilians who satisfied identical case criteria. All were evaluated for fibromyalgia (FM), multiple chemical sensitivity and psychiatric comorbidity. CFS was more likely to present in a sudden flu-like manner in civilians than veterans (p < .01) and comorbid FM was more prevalent in civilians (p < .01). These findings question the assumption that all patients with CFS suffer from the same underlying disorder.

 

Source: Ciccone DS, Weissman L, Natelson BH. Chronic fatigue syndrome in male Gulf war veterans and civilians: a further test of the single syndrome hypothesis. J Health Psychol. 2008 May;13(4):529-36. Doi: 10.1177/1359105308088525. https://www.ncbi.nlm.nih.gov/pubmed/18420761

 

Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome

Abstract:

Physiological and/or pathological implications of the dynamics of sleep stage transitions have not, to date, been investigated. We report detailed duration and transition statistics between sleep stages in healthy subjects and in others with chronic fatigue syndrome (CFS); in addition, we also compare our data with previously published results for rats.

Twenty-two healthy females and 22 female patients with CFS, characterized by complaints of unrefreshing sleep, underwent one night of polysomnographic recording. We find that duration of deep sleep (stages III and IV) follows a power-law probability distribution function; in contrast, stage II sleep durations follow a stretched exponential and stage I, and REM sleep durations follow an exponential function. These stage duration distributions show a gradually increasing departure from the exponential form with increasing depth of sleep toward a power-law type distribution for deep sleep, suggesting increasing complexity of regulation of deeper sleep stages. We also find a substantial number of REM to non-REM sleep transitions in humans, while this transition is reported to be virtually nonexistent in rats.

The relative frequency of this REM to non-REM sleep transition is significantly lower in CFS patients than in controls, resulting in a significantly greater relative transition frequency of moving from both REM and stage I sleep to awake. Such an alteration in the transition pattern suggests that the normal continuation of sleep in light or REM sleep is disrupted in CFS. We conclude that dynamic transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with pathophysiological implications.

 

Source: Kishi A, Struzik ZR, Natelson BH, Togo F, Yamamoto Y. Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome. Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1980-7. doi: 10.1152/ajpregu.00925.2007. Epub 2008 Apr 16. http://ajpregu.physiology.org/content/294/6/R1980.long

 

A real-time assessment of the effect of exercise in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report substantial symptom worsening after exercise. However, the time course over which this develops has not been explored. Therefore, the objective of this study was to investigate the influence of exercise on subjective symptoms and on cognitive function in CFS patients in natural settings using a computerized ecological momentary assessment method, which allowed us to track the effects of exercise within and across days.

Subjects were 9 female patients with CFS and 9 healthy women. A watch-type computer was used to collect real-time data on physical and psychological symptoms and cognitive function for 1 week before and 2 weeks after a maximal exercise test. For each variable, we investigated temporal changes after exercise using multilevel modeling.

Following exercise, physical symptoms did get worse but not until a five-day delay in CFS patients. Despite this, there was no difference in the temporal pattern of changes in psychological symptoms or in cognitive function after exercise between CFS patients and controls. In conclusion, physical symptoms worsened after several days delay in patients with CFS following exercise while psychological symptoms or cognitive function did not change after exercise.

 

Source: Yoshiuchi K, Cook DB, Ohashi K, Kumano H, Kuboki T, Yamamoto Y, Natelson BH. A real-time assessment of the effect of exercise in chronic fatigue syndrome. Physiol Behav. 2007 Dec 5;92(5):963-8. Epub 2007 Jul 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170105/ (Full article)

 

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

Abstract:

CONTEXT: Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

OBJECTIVE: To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

DESIGN: Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

SETTING: Referral practice and research center.

PARTICIPANTS: 60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

MAIN OUTCOME MEASURES: Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

RESULTS: CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

CONCLUSION: A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

 

Source: Natelson BH, Intriligator R, Cherniack NS, Chandler HK, Stewart JM. Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome. Dyn Med. 2007 Jan 30;6:2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796865/ (Full article)

 

The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome (CFS), accounting for comorbid fibromyalgia (FM) and controlling for aerobic fitness.

METHODS: Twenty-nine patients with CFS only, 23 patients with CFS plus FM, and 32 controls completed an incremental bicycle test to exhaustion. Cardiorespiratory and perceptual responses were measured. Results were determined for the entire sample and for 18 subjects from each group matched for peak oxygen consumption.

RESULTS: In the overall sample, there were no significant differences in cardiorespiratory parameters between the CFS only group and the controls. However, the CFS plus FM group exhibited lower ventilation, lower end-tidal CO2, and higher ventilatory equivalent of carbon dioxide compared with controls, and slower increases in heart rate compared with both patients with CFS only and controls. Peak oxygen consumption, ventilation, and workload were lower in the CFS plus FM group. Subjects in both the CFS only group and the CFS plus FM group rated exercise as more effortful than did controls. Patients with CFS plus FM rated exercise as significantly more painful than did patients with CFS only or controls. In the subgroups matched for aerobic fitness, there were no significant differences among the groups for any measured cardiorespiratory response, but perceptual differences in the CFS plus FM group remained.

CONCLUSION: With matching for aerobic fitness, cardiorespiratory responses to exercise in patients with CFS only and CFS plus FM are not different from those in sedentary healthy subjects. While CFS patients with comorbid FM perceive exercise as more effortful and painful than do controls, those with CFS alone do not. These results suggest that aerobic fitness and a concurrent diagnosis of FM are likely explanations for currently conflicting data and challenge ideas implicating metabolic disease in the pathogenesis of CFS.

 

Source: Cook DB, Nagelkirk PR, Poluri A, Mores J, Natelson BH. The influence of aerobic fitness and fibromyalgia on cardiorespiratory and perceptual responses to exercise in patients with chronic fatigue syndrome. Arthritis Rheum. 2006 Oct;54(10):3351-62. https://www.ncbi.nlm.nih.gov/pubmed/17009309

 

Patients with chronic fatigue syndrome have reduced absolute cortical blood flow

Abstract:

Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results. This may be because they used single-photon emission computed tomography to measure brain blood flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses were done after stratifying the CFS patients based on the presence or absence of a current psychiatric disorder.

Flow was diminished in both groups as follows: patients with no current psychiatric disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have reduced absolute cortical blood flow in rather broad areas when compared with data from healthy controls and that those devoid of psychopathology had the most reductions in cortical flow. These data support, in part, our earlier findings that patients devoid of psychopathology are the group most at risk of having some of the symptoms of CFS due to brain dysfunction.

 

Source: Yoshiuchi K, Farkas J, Natelson BH. Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging. 2006 Mar;26(2):83-6. https://www.ncbi.nlm.nih.gov/pubmed/16494597