Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine diurnal salivary cortisol rhythms and plasma IL-6 concentrations in persons with chronic fatigue syndrome (CFS), persons not fulfilling a diagnosis of CFS (we term them cases with insufficient symptoms or fatigue, ISF) and nonfatigued controls (NF). Previous studies of CFS patients have implicated the hypothalamic-pituitary-adrenal axis and the immune system in the pathophysiology of CFS, although results have been equivocal.

METHODS: Twenty-eight people with CFS, 35 persons with ISF, and 39 NF identified from the general population of Wichita, Kansas, were admitted to a research ward for 2 days. Saliva was collected immediately on awakening (6:30 AM), at 08:00 AM, 12 noon, 4:00 PM, 8:00 PM and at bedtime (10:00 PM) and plasma was obtained at 7:30 AM. Salivary cortisol concentrations were assessed using radioimmunoassay, and plasma IL-6 was measured using sandwich enzyme-linked immunosorbent assay.

RESULTS: People with CFS demonstrated lower salivary cortisol concentrations in the morning and higher salivary cortisol concentrations in the evening compared with both ISF and NF groups indicating a flattening of the diurnal cortisol profile. Mean plasma IL-6 concentrations were highest in CFS compared with the other groups, although these differences were no longer significant after controlling for BMI. Attenuated decline of salivary cortisol concentrations across the day and IL-6 concentration were associated with fatigue symptoms in CFS.

CONCLUSIONS: These results suggest an altered diurnal cortisol rhythm and IL-6 concentrations in CFS cases identified from a population-based sample.

 

Source: Nater UM, Youngblood LS, Jones JF, Unger ER, Miller AH, Reeves WC, Heim C. Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome. Psychosom Med. 2008 Apr;70(3):298-305. doi: 10.1097/PSY.0b013e3181651025. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378875

 

The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome

Abstract:

Hypocortisolism has been reported in chronic fatigue syndrome (CFS), with the significance of this finding to disease etiology unclear. This study examined cortisol levels and their relationships with symptoms in a group of 108 individuals with CFS. CFS symptoms examined included fatigue, pain, sleep difficulties, neurocognitive functioning, and psychiatric status. Alterations in cortisol levels were examined by calculation of mean daily cortisol, while temporal variation in cortisol function was examined by means of a regression slope. Additionally, deviation from expected cortisol diurnal pattern was determined via clinical judgment. Results indicated that fatigue and pain were associated with salivary cortisol levels. In particular, variance from the expected pattern of cortisol was associated with increased levels of fatigue. The implications of these findings are discussed.

 

Source: Torres-Harding S, Sorenson M, Jason L, Maher K, Fletcher MA, Reynolds N, Brown M. The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome. J Appl Biobehav Res. 2008 Jan 1;13:157-180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/ (Full article)

 

Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes

Abstract:

AIM: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. The authors have recently reported a study of gene expression that identified differential expression of 88 human genes in patients with CFS/ME. Clustering of quantitative PCR (qPCR) data from patients with CFS/ME revealed seven distinct subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes and severity.

METHODS: In this study, for each CFS/ME subtype, those genes whose expression differed significantly from that of normal blood donors were identified, and then gene interactions, disease associations and molecular and cellular functions of those gene sets were determined. Genomic analysis was then related to clinical data for each CFS/ME subtype.

RESULTS: Genomic analysis revealed some common (neurological, haematological, cancer) and some distinct (metabolic, endocrine, cardiovascular, immunological, inflammatory) disease associations among the subtypes. Subtypes 1, 2 and 7 were the most severe, and subtype 3 was the mildest. Clinical features of each subtype were as follows: subtype 1 (cognitive, musculoskeletal, sleep, anxiety/depression); subtype 2 (musculoskeletal, pain, anxiety/depression); subtype 3 (mild); subtype 4 (cognitive); subtype 5 (musculoskeletal, gastrointestinal); subtype 6 (postexertional); subtype 7 (pain, infectious, musculoskeletal, sleep, neurological, gastrointestinal, neurocognitive, anxiety/depression).

CONCLUSION: It was particularly interesting that in the seven genomically derived subtypes there were distinct clinical syndromes, and that those which were most severe were also those with anxiety/depression, as would be expected in a disease with a biological basis.

 

Source: Kerr JR, Burke B, Petty R, Gough J, Fear D, Mattey DL, Axford JS, Dalgleish AG, Nutt DJ. Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes. J Clin Pathol. 2008 Jun;61(6):730-9. Epub 2007 Dec 5. https://www.ncbi.nlm.nih.gov/pubmed/18057078

 

Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study

Abstract:

BACKGROUND: Complaints of unrefreshing sleep are a prominent component of chronic fatigue syndrome (CFS); yet, polysomnographic studies have not consistently documented sleep abnormalities in CFS patients. We conducted this study to determine whether alterations in objective sleep characteristics are associated with subjective measures of poor sleep quality in persons with CFS.

METHODS: We examined the relationship between perceived sleep quality and polysomnographic measures of nighttime and daytime sleep in 35 people with CFS and 40 non-fatigued control subjects, identified from the general population of Wichita, Kansas and defined by empiric criteria. Perceived sleep quality and daytime sleepiness were assessed using clinical sleep questionnaires. Objective sleep characteristics were assessed by nocturnal polysomnography and daytime multiple sleep latency testing.

RESULTS: Participants with CFS reported unrefreshing sleep and problems sleeping during the preceding month significantly more often than did non-fatigued controls. Participants with CFS also rated their quality of sleep during the overnight sleep study as significantly worse than did control subjects. Control subjects reported significantly longer sleep onset latency than latency to fall asleep as measured by PSG and MSLT. There were no significant differences in sleep pathology or architecture between subjects with CFS and control subjects.

CONCLUSION: People with CFS reported sleep problems significantly more often than control subjects. Yet, when measured these parameters and sleep architecture did not differ between the two subject groups. A unique finding requiring further study is that control, but not CFS subjects, significantly over reported sleep latency suggesting CFS subjects may have an increased appreciation of sleep behaviour that may contribute to their perception of sleep problems.

 

Source: Majer M, Jones JF, Unger ER, Youngblood LS, Decker MJ, Gurbaxani B, Heim C, Reeves WC. Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study. BMC Neurol. 2007 Dec 5;7:40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231384/ (Full article)

 

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