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

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.

2003 ◽  
Vol 15 (4) ◽  
pp. 184-191 ◽  
Author(s):  
Jens Gaab ◽  
Nicolas Rohleder ◽  
Vera Heitz ◽  
Tanja Schad ◽  
Veronika Engert ◽  
...  

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.


2019 ◽  
Vol 105 (3) ◽  
pp. e762-e773 ◽  
Author(s):  
Angelina Gideon ◽  
Christine Sauter ◽  
Judy Fieres ◽  
Thilo Berger ◽  
Britta Renner ◽  
...  

Abstract Context The renin-angiotensin-aldosterone system (RAAS) plays an important role in cardiovascular homeostasis and its dysfunction relates to negative health consequences. Acute psychosocial stress seems to activate the RAAS in humans, but stress kinetics and interrelations of RAAS parameters compared with a nonstress control group remain inconclusive. Objective We systematically investigated in a randomized placebo-controlled design stress kinetics and interrelations of the reactivity of RAAS parameters measured in plasma and saliva to standardized acute psychosocial stress induction. Methods 58 healthy young men were assigned to either a stress or a placebo control group. The stress group underwent the Trier Social Stress Test (TSST), while the control group underwent the placebo TSST. We repeatedly assessed plasma renin, and plasma and salivary aldosterone before and up to 3 hours after stress/placebo. We simultaneously assessed salivary cortisol to validate successful stress induction and to test for interrelations. Results Acute psychosocial stress induced significant increases in all endocrine measures compared with placebo-stress (all P ≤ .041). Highest renin levels were observed 1 minute after stress, and highest aldosterone and cortisol levels 10 and 20 minutes after stress, with salivary aldosterone starting earlier at 1 minute after stress. Renin completed recovery at 10 minutes, cortisol at 60 minutes, salivary aldosterone at 90 minutes, and plasma aldosterone at 180 minutes after stress. Stress increase scores of all endocrine measures related to each other, as did renin and cortisol areas under the curve with respect to increase (AUCi) and salivary and plasma aldosterone AUCi (all P ≤ .047). Conclusions Our findings suggest that in humans acute psychosocial stress induces a differential and interrelated RAAS parameter activation pattern. Potential implications for stress-related cardiovascular risk remain to be elucidated.


2002 ◽  
Vol 65 (10) ◽  
pp. 461-468 ◽  
Author(s):  
Diane L Cox

It has been stated that, although most chronic fatigue syndrome (CFS) patients can be treated in primary care and that cognitive behaviour therapy and prescribed, graded aerobic exercise appear to be promising in outpatient management, a minority of patients will require inpatient care (Royal Colleges of Physicians, General Practitioners and Psychiatrists 1996). To date, little has been written on the need for and impact of an inpatient approach for patients with CFS. This study builds on previous work to show how patients with complex CFS responded to a specifically designed occupational therapy inpatient programme, using the principles of cognitive behaviour therapy and graded activity. A quasi-experimental study was carried out using current inpatients with those on the waiting list as a comparison. At 6 months following discharge, a significant difference between the groups in terms of symptoms and level of ability was not demonstrated. However, a significant effect was shown in patients' perceived health, length of time tired and management of the illness. Thirty-one (72%) of the inpatient group, compared with 10 (53%) of the comparison group, stated that they felt better than the previous year. Thirty-one (72%) of the inpatient group, compared with 7 (37%) of the comparison group, indicated better management of their illness. These findings give some evidence of the need for an inpatient CFS management programme for specific patients with complex CFS.


2020 ◽  
Author(s):  
C (Linda) MC van Campen ◽  
Peter C Rowe ◽  
Freek WA Verheugt ◽  
Frans C Visser

Abstract Background most studies to assess effort intolerance in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have used questionnaires. Few studies have compared questionnaires with objective measures like an actometer or an exercise test. Therefore three measures of physical activity in ME/CFS patients, being the physical functioning scale (PFS) of the SF-36, the number of steps/day (Steps) of an actometer and the %peak VO 2 of a cardiopulmonary stress test were compared. Methods female ME/CFS patients were selected from a clinical database if the three types of measurements were available, and the interval between measurements was ≤ three months. Data of the three measures were compared by linear regression. Results in 99 female patients the three different measures were linearly, significantly and positively correlated (PFS vs Steps, PFS vs %peak VO 2 and Steps vs %peak VO 2 : all P<0.001). Subgroup analysis showed that the relations between the three measures were not different in patients with versus without fibromyalgia and with versus without a maximal exercise effort (RER≥1.1). In 20 patients re-evaluated for symptom worsening, the mean of all three measures was significantly lower (P<0.0001), strengthening the observation of the relations between them. Despite the close correlation a large variation was observed between the three measures in individual patients. Conclusions given the large variation in ME/CFS patients, the use of only one type of measurement is inadequate. Integrating the three modalities may be useful for patient care by detecting overt discrepancies and may aid study designs aimed at improving exercise capacity.


2021 ◽  
Author(s):  
Ruud Raijmakers ◽  
Megan E. Roerink ◽  
Stephan P. Keijmel ◽  
Leo A.B. Joosten ◽  
Mihai G. Netea ◽  
...  

Abstract Background The pathophysiology of chronic fatigue syndrome (CFS) and Q fever fatigue syndrome (QFS) remains elusive. Recent data suggest a role for neuroinflammation as defined by increased expression of translocator protein (TSPO). In the present study we investigated neuroinflammation in female CFS and QFS patients compared with healthy women, using Positron Emission Tomography (PET) with the TSPO ligand [11C]-PK11195. Methods The study population consisted of CFS patients (n = 9), QFS patients (n = 10), and healthy controls (n = 9). All subjects were women, matched for age (± 5 years) and neighbourhood, between 18 and 59 years of age, who did not use any medication other than paracetamol or oral contraceptives, and were not vaccinated in the last six months. None of the subjects reported substance abuse in the past 3 months or reported signs of underlying psychiatric disease on the Mini-International Neuropsychiatric Interview (MINI). All subjects underwent a [11C]-PK11195 PET scan and the [11C]-PK11195 binding potential (BPND) was calculated. Results No statistically significant differences in BPND were found for CFS patients or QFS patients when compared to healthy controls. BPND of [11C]-PK11195 positively correlated with symptom severity scores in QFS patients, but a negative correlation was found in CFS patients. Conclusions In contrast to what was previously reported for CFS, we found no significant difference in BPND of [11C]-PK11195 when comparing CFS or QFS patients to healthy neighbourhood controls. In this small series we were unable to find signs of neuroinflammation in patients with CFS and QFS. Trial registration EudraCT number: 2014-004448-37


2000 ◽  
Vol 63 (4) ◽  
pp. 163-170 ◽  
Author(s):  
Lucy Moore

This study aimed to establish the attitudes of occupational therapists towards chronic fatigue syndrome. Previously, no study had investigated the attitudes of health professionals towards this condition, which may be a factor in maintaining the uncertainty surrounding chronic fatigue syndrome. Twenty occupational therapists practising in either physical or mental health settings were recruited to this study. In order to achieve a depth of knowledge not gained by previous studies, the data were collected through a combination of quantitative and qualitative methodology by using a structured questionnaire and a semi-structured interview; the findings were analysed statistically and thematically. At variance with the literature, the results revealed a neutral to positive attitude towards chronic fatigue syndrome, with no significant difference in responses from participants practising in physical or mental health settings. A unique and valuable role was clearly identified for the profession of occupational therapy within the wider multidisciplinary framework. However, as 16 (80%) of the participants had met individuals with chronic fatigue syndrome, the lack of knowledge and need for further education and training were highlighted. Continuing professional development is fundamental in order to provide appropriate, sensitive and holistic services in the future for all individuals with chronic fatigue syndrome.


2013 ◽  
Vol 43 (10) ◽  
pp. 2227-2235 ◽  
Author(s):  
P. D. White ◽  
K. Goldsmith ◽  
A. L. Johnson ◽  
T. Chalder ◽  
M. Sharpe

BackgroundA multi-centre, four-arm trial (the PACE trial) found that rehabilitative cognitive behaviour therapy (CBT) and graded exercise therapy (GET) were more effective treatments for chronic fatigue syndrome (CFS) than specialist medical care (SMC) alone, when each was added to SMC, and more effective than adaptive pacing therapy (APT) when added to SMC. In this study we compared how many participants recovered after each treatment.MethodWe defined recovery operationally using multiple criteria, and compared the proportions of participants meeting each individual criterion along with two composite criteria, defined as (a) recovery in the context of the trial and (b) clinical recovery from the current episode of the illness, however defined, 52 weeks after randomization. We used logistic regression modelling to compare treatments.ResultsThe percentages (number/total) meeting trial criteria for recovery were 22% (32/143) after CBT, 22% (32/143) after GET, 8% (12/149) after APT and 7% (11/150) after SMC. Similar proportions met criteria for clinical recovery. The odds ratio (OR) for trial recovery after CBT was 3.36 [95% confidence interval (CI) 1.64–6.88] and for GET 3.38 (95% CI 1.65–6.93), when compared to APT, and after CBT 3.69 (95% CI 1.77–7.69) and GET 3.71 (95% CI 1.78–7.74), when compared to SMC (p values ⩽0.001 for all comparisons). There was no significant difference between APT and SMC. Similar proportions recovered in trial subgroups meeting different definitions of the illness.ConclusionsThis study confirms that recovery from CFS is possible, and that CBT and GET are the therapies most likely to lead to recovery.


2019 ◽  
Vol 2 (2) ◽  
pp. 8
Author(s):  
Shumei Bai ◽  
Ling Shui ◽  
Qin Si ◽  
Yingsong Chen

Objective: To observe the effects of warm acupuncture on “Dinghui Acupoint” and “Heart Acupoint” in Traditional Mongolian Medicine on behavior and hypothalamic inflammatory cytokines IL-1β, IL-6 and IFN-r in Rats with Chronic Fatigue Syndrome. Methods: SD rats were randomly divided into normal group, model group, warm acupuncture group and moxibustion positive control group. The latter three groups of rats were used to establish a model of rats with chronic fatigue syndrome (CFS) using a combination of physical fatigue and mental fatigue. When establishing the model of warm acupuncture group, “Dinghui Acupoint” and “Heart Acupoint” intervention was carried out; when establishing the model of moxibustion positive control group, “Zusanli Acupoint” intervention was carried out on both sides. Behavioral observations (body weight, exhaustive swimming time, tail suspension experiment, water maze) were performed before and after modeling. The hypothalamic inflammatory cytokines IL-1β, IL-6 and IFN-r were detected by ELISA method after warm acupuncture and moxibustion intervention. Results: After 21 days of modeling, the body weight of the rats in each group was significantly lower than that in the normal group, and there was a significant difference (P<0.01); Compared with the model group, the weight of the rats in the warm acupuncture group increased significantly, and there was a significant difference (P<0.01); Compared with the model group, the exhaustive swimming time of the rats in the warm acupuncture group was significantly prolonged, and there was a significant difference (P<0.01); Compared with the moxibustion group, the exhaustion time of the rats in the warm acupuncture group was relatively prolonged, and there was a significant difference (P<0.05); Compared with the normal group, the tail suspension time of the model group was significantly prolonged, and there was a significant difference (P<0.05); Compared with the model group, there was a significant difference in the duration of the suspension of the warm acupuncture group and the moxibustion group (P<0.01); Compared with the normal group, the total distance of the water maze test was shorter in the model group, and there was a significant difference (P<0.01); Compared with the model group, both the warm acupuncture group and the moxibustion group were prolonged, and there was a significant difference (P<0.05); Compared with the moxibustion group, the distance between the rats in the warm acupuncture group was relatively longer, but there was no significant difference (P>0.05); Compared with the normal group, IL-1β, IL-6 and IFN-r increased significantly in the model group and there was a significant difference (P<0.05); Compared with the model group, IL-1β and IL-6 in the warm acupuncture group was significantly decreased (P<0.05), and the IL-6 in the moxibustion group was significantly different (P<0.05); Compared with the model group, there was no significant difference between the IFN-r group and the moxibustion group (P>0.05); Compared with the moxibustion group, the levels of IL-1β, IL-6 and IFN-r were not significantly different (P>0.05). Conclusion: Warm acupuncture on “Dinghui Acupoint” and “Heart Acupoint” in Traditional Mongolian Medicine has the ability to improve the body’s defense and self-healing ability, improve chronic fatigue syndrome (CFS), and thus play a preventive role. The results of this research indicate that the warm acupuncture group and the moxibustion group have the same effect.


2011 ◽  
Vol 23 (11) ◽  
pp. 3218-3227 ◽  
Author(s):  
Franziska Plessow ◽  
Rico Fischer ◽  
Clemens Kirschbaum ◽  
Thomas Goschke

Dynamically adjusting the right amount of goal shielding to varying situational demands is associated with the flexibility of cognitive control, typically linked with pFC functioning. Although stress hormones are found to also bind to prefrontal receptors, the link between stress and cognitive control remains elusive. Based on that, we aimed at investigating effects of acute psychosocial stress on dynamic control adjustments. Forty-eight healthy volunteers were exposed to either a well-established stress induction protocol (the Trier Social Stress Test, TSST) or a standardized control situation before a selective attention (Simon) task involving response conflicts. The individual physiological stress response was monitored by analyzing levels of free cortisol and α-amylase activity in saliva samples showing that the TSST reliably induced an increase of endogenous stress hormone levels. Acute stress did not inevitably impair cognitive functioning, however, as stressed participants showed tonically increased goal shielding (to reduce interference) at the expense of decreased cognitive flexibility. Importantly, as a novel finding in humans, stress effects on cognitive functions were not present immediately after the stress experience but developed gradually over time and, therefore, paralleled the time course of the hypothalamus–pituitary–adrenal (HPA) stress response. In addition, the total increase of individual cortisol levels reflecting HPA activity, but not the total changes in α-amylase activity associated with sympathetic activity, was reversely related to the amount of cognitive flexibility in the final block of testing. Our study provides evidence for a stress-induced time-dependent decrease of cognitive flexibility that might be related to changes in cortisol levels.


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