Enhanced glucocorticoid sensitivity in patients with chronic fatigue syndrome

2003 ◽  
Vol 15 (4) ◽  
pp. 184-191 ◽  
Author(s):  
Jens Gaab ◽  
Nicolas Rohleder ◽  
Vera Heitz ◽  
Tanja Schad ◽  
Veronika Engert ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Social Stress ◽  
Stress Test ◽  
Chronic Fatigue ◽  
Trier Social Stress Test ◽  
Healthy Controls ◽  
Necrosis Factor Alpha ◽  
Enhanced Sensitivity ◽  
Fatigue Syndrome

Objective:Alterations of the immune–neuroendocrine interplay have been described in chronic fatigue syndrome (CFS). Employing a recently developed method, the study set out to investigate whether patients with CFS have an altered sensitivity to glucocorticoids (GCs) when under stress.Methods:A total of 21 CFS patients and 20 healthy age- and gender-matched controls underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). Salivary and plasma cortisol levels were measured repeatedly following exposure to the stressor. GC sensitivity was assessedin vitroby dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNC-α).Results:Cortisol responses following the TSST did not differ significantly between CFS patients and healthy controls. GC sensitivity differed significantly between CFS patients and healthy controls, with CFS patients showing a greater sensitivity towards GCs (TNF-α:F1/39= 7.32,P= 0.01; IL-6:F1/39= 9.73,P= 0.004).Conclusion:Consistent with recent evidence, CFS patients are characterized by an enhanced sensitivity to glucocorticoids. The implications for secondary processes, such as the regulatory influence of glucocorticoids on immune processes, are discussed.

scholarly journals Acute Psychosocial Stress-Mediated Changes in the Expression and Methylation of Perforin in Chronic Fatigue Syndrome

2013 ◽  
Vol 5 ◽  
pp. GEG.S10944 ◽  
Author(s):  
Virginia R. Falkenberg ◽  
Toni Whistler ◽  
Janna R. Murray ◽  
Elizabeth R. Unger ◽  
Mangalathu S. Rajeevan
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Whole Blood ◽  
Psychosocial Stress ◽  
Stress Test ◽  
Chronic Fatigue ◽  
Trier Social Stress Test ◽  
Cpg Sites ◽  
Fatigue Syndrome ◽  
Significant Difference ◽  
Acute Psychosocial Stress

Perforin ( PRF1) is essential for immune surveillance and studies report decreased perforin in chronic fatigue syndrome (CFS), an illness potentially associated with stress and/or infection. We hypothesize that stress can influence regulation of PRF1 expression, and that this regulation will differ between CFS and non-fatigued (NF) controls. We used the Trier Social Stress Test (TSST) as a standardized acute psychosocial stress, and evaluated its effect on PRF1 expression and methylation in CFS (n = 34) compared with NF (n = 47) participants. During the TSST, natural killer (NK) cells increased significantly in both CFS ( P = <0.0001) and NF subjects ( P = <0.0001). Unlike previous reports, there was no significant difference in PRF1 expression at baseline or during TSST between CFS and NF. However, whole blood PRF1 expression increased 1.6 fold during the TSST in both CFS ( P = 0.0003) and NF ( P = <0.0001). Further, the peak response immediately following the TSST was lower in CFS compared with NF ( P = 0.04). In addition, at 1.5 hours post TSST, PRF1 expression was elevated in CFS compared with NF (whole blood, P = 0.06; PBMC, P = 0.02). Methylation of seven CpG sites in the methylation sensitive region of the PRF1 promoter ranged from 38%-79% with no significant differences between CFS and NF. Although, the average baseline methylation of all seven CpG sites did not differ between CFS and NF groups, it showed a significant negative correlation with PRF1 expression at all TSST time points in both CFS (r = –0.56, P = <0.0001) and NF (r = –0.38, P = <0.0001). Among participants with high average methylation (≥65%), PRF1 expression was significantly lower in CFS than NF subjects immediately following TSST. These findings suggest methylation could be an important epigenetic determinant of inter-individual differences in PRF1 expression and that the differences in PRF1 expression and methylation between CFS and NF in the acute stress response require further investigation.

Comparison of the finger plethysmography derived stroke volumes by Nexfin CO Trek and suprasternal aortic Doppler derived stroke volume measurements in adults with myalgic encephalomyelitis/chronic fatigue syndrome and in healthy controls

2021 ◽  
pp. 1-14
Author(s):  
C. (Linda) M.C. van Campen ◽  
Freek W.A. Verheugt ◽  
Peter C. Rowe ◽  
Frans C. Visser
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Stroke Volume ◽  
Chronic Fatigue ◽  
Calibration Procedure ◽  
Myalgic Encephalomyelitis ◽  
Tilt Test ◽  
Healthy Controls ◽  
Tilt Testing ◽  
Fatigue Syndrome ◽  
Finger Plethysmography

BACKGROUND: Finger plethysmography derived stroke volumes are frequently measured during tilt table testing. There are two algorithms to determine stroke volumes: Modelflow and NexfinCO Trek. Most tilt studies used Modelflow, while there are differences between the two algorithms. OBJECTIVE: To compare stroke volume indices by Nexfin CO Trek (SVINexfinCOTrek) with suprasternal Doppler derived SVI (SVIDoppler) in healthy controls (HC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients during tilt testing. These patients may have a large SVI decrease during the tilt enabling a large range of SVI to be studied. METHODS: One hundred and fifty-four patients and 39 HC with a normal tilt test were included. Supine and end-tilt SVIDoppler and SVINexfinCOTrek were compared using the Bland-Altman analysis. Also, the effect of calibrating supine SVINexfinCOTrek to SVIDoppler was studied RESULTS: Supine and end-tilt SVINexfinCOTrek were significantly higher than SVIDoppler: both P< 0.005. Bias, limits of agreement, and percent error (PE) were high with PE’s between 37 and 43%. The calibration procedure resulted in an acceptable variance with a PE of 29%. CONCLUSIONS: SVINexfinCOTrek overestimates stroke volumes compared to SVIDoppler, leading to high PE’s. Calibration reduced variance to an acceptable level, allowing SVINexfinCOTrek to be used for assessment of SVI changes during tilt testing

scholarly journals Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Rosa María Escorihuela ◽  
Lluís Capdevila ◽  
Juan Ramos Castro ◽  
María Cleofé Zaragozà ◽  
Sara Maurel ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Chronic Fatigue Syndrome ◽  
Frequency Domain ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Healthy Controls ◽  
Fatigue Syndrome ◽  
Potential Biomarker ◽  
Fatigue Severity

Abstract Background Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME. Methods In this case–control study, 45 female patients who met the 1994 CDC/Fukuda definition for CFS/ME and 25 age- and gender-matched healthy controls underwent HRV recording-resting state tests. The intervals between consecutive heartbeats (RR) were continuously recorded over three 5-min periods. Time- and frequency-domain analyses were applied to estimate HRV variables. Demographic and clinical features, and self-reported symptom measures were also recorded. Results CFS/ME patients showed significantly higher scores in all symptom questionnaires (p < 0.001), decreased RR intervals (p < 0.01), and decreased HRV time- and frequency-domain parameters (p < 0.005), except for the LF/HF ratio than in the healthy controls. Overall, the correlation analysis reached significant associations between the questionnaires scores and HRV time- and frequency-domain measurements (p < 0.05). Furthermore, separate linear regression analyses showed significant relationships between self-reported fatigue symptoms and mean RR (p = 0.005), RMSSD (p = 0.0268) and HFnu indices (p = 0.0067) in CFS/ME patients, but not in healthy controls. Conclusions Our findings suggest that ANS dysfunction presenting as increased sympathetic hyperactivity may contribute to fatigue severity in individuals with ME/CFS. Further studies comparing short- and long-term HRV recording and self-reported outcome measures with previous studies in larger CFS/ME cohorts are urgently warranted.

Screening for Psychiatric Morbidity in Subjects Presenting with Chronic Fatigue Syndrome

1996 ◽  
Vol 168 (3) ◽  
pp. 354-358 ◽  
Author(s):  
Anne Farmer ◽  
Helen Chubb ◽  
Irene Jones ◽  
Janis Hillier ◽  
Andy Smith ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Serial Correlation ◽  
General Health Questionnaire ◽  
Psychiatric Morbidity ◽  
Correlation Coefficients ◽  
Chronic Fatigue ◽  
Healthy Controls ◽  
Operating Characteristics ◽  
Fatigue Syndrome ◽  
Icd 10

BackgroundThere is a need for a valid self-rating questionnaire to screen for psychiatric morbidity in patients with chronic fatigue syndrome (CFS). This study had the aim of assessing the utility and validity of two commonly used measures.MethodScores obtained on the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were compared with various diagnostic and severity ratings obtained via a validating clinical interview, the Schedules for the Clinical Assessment of Neuropsychiatry (SCAN) in 95 consecutively referred subjects at a medical out-patient clinic who fulfilled standard criteria for CFS, and 48 healthy controls. Outcome measures were validating coefficients and receiver operating characteristics (ROC) for different thresholds and scoring on GHQ and BDI and index of definition (ID) as measured by SCAN; and Pearson and point by serial correlation coefficients for different diagnostic groups derived via SCAN and defined according to ICD–10 and DSM–III–R.ResultsGHQ and BDI perform poorly as screeners of psychiatric morbidity in CFS subjects when compared with various SCAN derived ratings although results for controls are comparable with other studies.ConclusionsNeither the GHQ nor BDI alone can be recommended as screeners for psychiatric morbidity in CFS subjects.

scholarly journals Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study

Diagnostics ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 41 ◽  
Author(s):  
Nacul ◽  
de Barros ◽  
Kingdon ◽  
Cliff ◽  
Clark ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Cross Sectional Study ◽  
Myalgic Encephalomyelitis ◽  
Activity Levels ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
Fatigue Syndrome ◽  
Laboratory Test Results

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease presenting with extreme fatigue, post-exertional malaise, and other symptoms. In the absence of a diagnostic biomarker, ME/CFS is diagnosed clinically, although laboratory tests are routinely used to exclude alternative diagnoses. In this analytical cross-sectional study, we aimed to explore potential haematological and biochemical markers for ME/CFS, and disease severity. We reviewed laboratory test results from 272 people with ME/CFS and 136 healthy controls participating in the UK ME/CFS Biobank (UKMEB). After corrections for multiple comparisons, most results were within the normal range, but people with severe ME/CFS presented with lower median values (p < 0.001) of serum creatine kinase (CK; median = 54 U/L), compared to healthy controls (HCs; median = 101.5 U/L) and non-severe ME/CFS (median = 84 U/L). The differences in CK concentrations persisted after adjusting for sex, age, body mass index, muscle mass, disease duration, and activity levels (odds ratio (OR) for being a severe case = 0.05 (95% confidence interval (CI) = 0.02–0.15) compared to controls, and OR = 0.16 (95% CI = 0.07–0.40), compared to mild cases). This is the first report that serum CK concentrations are markedly reduced in severe ME/CFS, and these results suggest that serum CK merits further investigation as a biomarker for severe ME/CFS.

scholarly journals Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

2020 ◽  
Vol 21 (3) ◽  
pp. 1142
Author(s):  
Daniel Missailidis ◽  
Oana Sanislav ◽  
Claire Y. Allan ◽  
Sarah J. Annesley ◽  
Paul R. Fisher
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Sensitivity And Specificity ◽  
Respiratory Function ◽  
Death Rate ◽  
Frozen Storage ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Healthy Controls ◽  
Fatigue Syndrome ◽  
Mitochondrial Respiratory

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood mononuclear cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase Target Of Rapamycin Complex 1 (TORC1). These differences were correlated with disease severity, as measured by the Richardson and Lidbury weighted standing test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here, we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and receiver operating characteristic (ROC) curve analysis. We found that results from three different tests—lymphocyte death rate, mitochondrial respiratory function and TORC1 activity—could each individually serve as a biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination, they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.

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