Twin analyses of fatigue

Abstract:

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects.

 

Source: Schur E, Afari N, Goldberg J, Buchwald D, Sullivan PF. Twin analyses of fatigue. Twin Res Hum Genet. 2007 Oct;10(5):729-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953372/ (Full article)

 

Estimation of fatigue state in patient with CFS using actigraph and R-R interval power spectrum analysis]

Abstract:

OBJECTIVES: In this study, we try to estimate the fatigue state using actigraphy and R-R interval power spectrum analysis.

RESULTS: Actigraphy analysis showed that mean awake activity was decreased and duration of sleep was prolonged in patients with chronic fatigue syndrome (CFS), significantly (p < 0.001). Both of sleep episodes in wake period and wake episodes in sleep period were significantly increased in CFS patients in comparison with healthy volunteers (p < 0.001) In autonomic nerve analysis, sleep/awake ratio of high frequency component was significantly decreased in patients with CFS (p < 0.05).

CONCLUSION: The quality of sleep in patients with CFS was decreased because of increase of wake episodes in sleep period. Also the lack of parasympathetic activation during sleep period might be associated with the deterioration of sleep quality in patients with CFS.

 

Source: Tajima S, Kuratsune H, Yamaguti K, Takahashi A, Takashima S, Watanabe Y, Nishizawa Y. Estimation of fatigue state in patient with CFS using actigraph and R-R interval power spectrum analysis. Nihon Rinsho. 2007 Jun;65(6):1057-64. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561697

 

Evaluation of fatigue by using acceleration plethysmography

Abstract:

We evaluated the fatigue of patients with chronic fatigue syndrome by using acceleration plethysmography. The changes in the acceleration plethysmography were relatively dominant in the sympathetic nervous system from the viewpoint of the autonomic nervous system, and the fluctuation in the time-series data of the acceleration plethysmography was decreased from the viewpoint of chaos or complexity system. We found the relation between the level of fatigue and the changes in acceleration plethysmography. Therefore, the acceleration plethysmography might be useful for the evaluation of fatigue.

 

Source: Yamaguti K. Evaluation of fatigue by using acceleration plethysmography. Nihon Rinsho. 2007 Jun;65(6):1034-42. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561694

 

Sleep disturbance in chronic fatigue syndrome

Abstract:

Attempts to elucidate the complex pathophysiology of chronic fatigue syndrome (CFS) must consider subjective and objective sleep. Several reports of CFS showed the high rate of sleep disturbance such as insomnia, hypersomnia, circadian rhythm sleep disorder, sleep apnea/hypopnea syndrome and so on. To analyze pulse wave continuously in sleep of CFS patients by laser blood flowmeter, we set base line component (0.01-0.08 Hz) and pulse wave component(0.70-1.50 Hz). Results of FFT analysis indicate that the CFS can have at least three subtypes of pulse dynamics in sleep. There probably are different types of illnesses now contained within the CFS construct, in which identifying subtypes of sleep disturbance can be one important key.

 

Source: Kumano-go T, Adachi H, Sugita Y. Sleep disturbance in chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1017-22. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561691

 

Clinical features of chronic fatigue syndrome–symptoms

Abstract:

Chronic fatigue syndrome (CFS) is a clinically defined condition characterized by long-lasting disabling fatigue, resulting in severe impairment in daily functioning and associated symptoms such as memory and concentration difficulties, muscle aches, sleep disturbances, and headache. Common symptoms encountered in CFS patients were reviewed and top 10 common symptoms were described in detail with special reference to the particular features of each symptom helpful to diagnose CFS.

 

Source: Ban N, Saiki T, Ko G, Kuwahata A. Clinical features of chronic fatigue syndrome—symptoms. Nihon Rinsho. 2007 Jun;65(6):1011-5. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561690

 

The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with altered amounts of slow wave sleep, which could reflect reduced delta electroencephalograph (EEG) activity and impaired sleep regulation. To evaluate this hypothesis, we examined the response to a sleep regulatory challenge in CFS.

DESIGN: The first of 3 consecutive nights of study served as laboratory adaptation. Baseline sleep was assessed on the second night. On the third night, bedtime was delayed by 4 hours, followed by recovery sleep. Total available sleep time was held constant on all nights.

SETTING: A research sleep laboratory.

PARTICIPANTS: 13 pairs of monozygotic twins discordant for CFS.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: Power spectral analysis quantified slow wave activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2, 3, or 4) on each night. To ensure comparability, analyses were restricted to the first 4 NREM periods on each night. Data were coded for NREM period and twin pair. Repeated-measures analysis of variance (ANOVA) contrasted sleep delay effects across NREM periods between twin pairs. A second ANOVA calculated the SWA in each NREM period in recovery sleep relative to baseline SWA. The 2 groups of twins were similar on baseline SWA power. After sleep delay, CFS twins exhibited significantly less SWA power in the first NREM period of recovery sleep and accumulated a smaller percentage of SWA in the first NREM period than their co-twins.

CONCLUSIONS: CFS is associated with a blunted SWA response to sleep challenge, suggesting that the basic sleep drive and homeostatic response are impaired.

 

Source: Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome, Sleep. 2007 May;30(5):657-62. https://www.ncbi.nlm.nih.gov/pubmed/17552382

 

Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVE: Individuals with chronic fatigue syndrome (CFS) experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their cotwins without CFS.

DESIGN: Cotwin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS.

PATIENTS AND SETTING: Fifteen monozygotic twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington.

RESULTS: Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their cotwins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain (P = 0.003) and fatigue (P < 0.001) by their cotwins without CFS.

CONCLUSIONS: These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS.

 

Source: Ullrich PM, Afari N, Jacobsen C, Goldberg J, Buchwald D. Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome. Pain Med. 2007 Apr;8(3):216-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957294/ (Full article)

 

Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances.

METHODS: Forty-eight patients who fulfilled 1994 Centers for Disease Control and Prevention criteria for CFS underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2′,5′-oligoadenylate trimer. Basic descriptive statistical parameters were calculated.

RESULTS: Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L.

CONCLUSIONS: The main findings are 1) validation of sleep latency problems and other sleep disturbances as already suggested by several authors; 2) alpha-delta intrusion seems associated with anxiety; and 3) elevated RNase L did not correlate with alpha-delta sleep.

 

Source: Van Hoof E, De Becker P, Lapp C, Cluydts R, De Meirleir K. Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome. Am J Med Sci. 2007 Feb;333(2):78-84. https://www.ncbi.nlm.nih.gov/pubmed/17301585

 

Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome

Abstract:

In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS.

This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc.

 

Source: Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2007 Apr;26(4):465-73. Epub 2006 Nov 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1820749/ (Full article)

 

Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study

Abstract:

BACKGROUND: The etiology and pathophysiology of chronic fatigue syndrome (CFS) remain inchoate. Attempts to elucidate the pathophysiology must consider sleep physiology, as unrefreshing sleep is the most commonly reported of the 8 case-defining symptoms of CFS. Although published studies have consistently reported inefficient sleep and documented a variable occurrence of previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS.

METHODS: This study recruited CFS cases and non-fatigued controls from a population based study of CFS in Wichita, Kansas. Participants spent two nights in the research unit of a local hospital and underwent overnight polysomnographic and daytime multiple sleep latency testing in order to characterize sleep architecture.

RESULTS: Approximately 18% of persons with CFS and 7% of asymptomatic controls were diagnosed with severe primary sleep disorders and were excluded from further analysis. These rates were not significantly different. Persons with CFS had a significantly higher mean frequency of obstructive apnea per hour (p = .003); however, the difference was not clinically meaningful. Other characteristics of sleep architecture did not differ between persons with CFS and controls.

CONCLUSION: Although disordered breathing during sleep may be associated with CFS, this study generally did not provide evidence that altered sleep architecture is a critical factor in CFS. Future studies should further scrutinize the relationship between subjective sleep quality relative to objective polysomnographic measures.

 

Source: Reeves WC, Heim C, Maloney EM, Youngblood LS, Unger ER, Decker MJ, Jones JF, Rye DB. Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study. BMC Neurol. 2006 Nov 16;6:41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1660569/ (Full article)