Fatigue In Chronic Fatigue Syndrome Research Articles

Effect of Prolong-life-with-nine-turn-method (Yan Nian Jiu Zhuan) Qigong on fatigue and gastrointestinal function in patients with chronic fatigue syndrome: Study protocol for a randomized controlled trial.

Chronic fatigue syndrome (CFS) is a physical and mental disorder in which long-term fatigue is the main symptom. CFS patients are often accompanied by functional gastrointestinal diseases (FGIDs), which lead to decreased quality of life and increased fatigue. Prolong-life-with-nine-turn-method (PLWNT) is a kind of physical and mental exercise. Its operation includes adjusting the mind, breathing and cooperating with eight self-rubbing methods and one upper body rocking method. PLWNT was used to improve the digestive function in ancient China and to treat FGIDs such as functional dyspepsia and irritable bowel syndrome in modern times. Previous studies have shown that PLWNT can reduce fatigue in patients with CFS. But it is unclear whether the effect of PLWNT on CFS fatigue is related to gastrointestinal function. The aim of this study was to explore the relationship between PLWNT and fatigue and gastrointestinal function in patients with CFS. This study is a non-inferiority randomized controlled trial (RCT). The whole study period is 38 weeks, including 2 weeks of baseline evaluation, 12 weeks of intervention and 6 months of follow-up. Ninety-six CFS patients will be stratified random assigned to the intervention group (PLWNT) and the control group (cognitive behavior treatment) in the ratio of 1:1 through the random number table generated by SPSS. In the evaluation of results, Multidimensional Fatigue Inventory-20 (MFI-20), Gastrointestinal Symptom Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), and Short Form 36 item health survey (SF-36) will be evaluated at week 0 (baseline), week 6 (midterm), week 12 (endpoint) and month 9 (follow up). The intestinal flora will be evaluated at week 0 (baseline) and week 12 (endpoint). The data results will be processed by statistical experts. The data analysis will be based on the intention to treat principle and per-protocol analysis. In the efficacy evaluation, repeated measurement analysis of variance will be used for data conforming to normal distribution or approximate normal distribution. The data which do not conform to the analysis of repeated measurement variance will be analyzed by the generalized estimation equation Linear discriminant analysis will be used to clarify the difference species of intestinal flora. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. This trial will provide evidence to PLWNT exerting positive effects on fatigue and gastrointestinal function of CFS. It will further explore whether the improvement of PLWNT on CFS fatigue is related to gastrointestinal function. The trial was registered at Chinese Clinical Trial Registry http://www.chictr.org.cn/showproj.aspx?proj=151456 (Registration No.: ChiCTR2200056530). Date: 2022-02-07.

Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome

ObjectiveTo explore changes in autonomic functioning, sleep, and physical activity during a post-exertional symptom exacerbation induced by physical or cognitive challenge in participants with chronic fatigue syndrome (CFS). MethodsThirty-five participants with CFS reported fatigue levels 24-h before, immediately before, immediately after, and 24-h after the completion of previously characterised physical (stationary cycling) or cognitive (simulated driving) challenges. Participants also provided ratings of their sleep quality and sleep duration for the night before, and after, the challenge. Continuous ambulatory electrocardiography (ECG) and physical activity was recorded from 24-h prior, until 24-h after, the challenge. Heart rate (HR) and HR variability (HRV, as high frequency power in normalized units) was derived from the ECG trace for periods of wake and sleep. ResultsBoth physical and cognitive challenges induced an immediate exacerbation of the fatigue state (p<0.001), which remained elevated 24-h post-challenge. After completing the challenges, participants spent a greater proportion of wakeful hours lying down (p=0.024), but did not experience significant changes in sleep quality or sleep duration. Although the normal changes in HR and HRV during the transition from wakefulness to sleep were evident, the magnitude of the increase in HRV was significantly lower after completing the challenge (p=0.016). ConclusionPreliminary evidence of reduced nocturnal parasympathetic activity, and increased periods of inactivity, were found during post-exertional fatigue in a well-defined group of participants with CFS. Larger studies employing challenge paradigms are warranted to further explore the underlying pathophysiological mechanisms of post-exertional fatigue in CFS.

Fatigue and psychosocial variables in autoimmune rheumatic disease and chronic fatigue syndrome: A cross-sectional comparison

ObjectiveFatigue is common in autoimmune rheumatic diseases (ARD). This study compared symptom-related cognitions, beliefs, behaviours, quality of sleep, lack of acceptance and distress in participants with ARD such as rheumatoid arthritis (RA), seronegative spondyloarthropathy (SpA), and connective tissue disease (CTD), and participants with chronic fatigue syndrome (CFS). Methods303 participants with RA, SpA, CTD and CFS completed questionnaire measures of fatigue, social adjustment, cognitive-behavioural responses, lack of acceptance, distress and quality of sleep. The RA, SpA and CTD groups were first compared with each other. They were then combined into one group and compared with the CFS group. ResultsThere were no statistically significant differences between the RA, SpA or CTD groups for any of the measures. The CFS group was more fatigued, reported more distress and sleep disturbance and had worse social adjustment than the ARD group after adjustment for age and illness duration. After adjustment for fatigue, age, and illness duration, the CFS group scored more highly on lack of acceptance and avoidance/resting behaviour while the ARD group showed significantly higher levels of catastrophizing, damage beliefs, and symptom focusing than the CFS group. ConclusionFatigue in rheumatic diseases may be perpetuated by similar underlying transdiagnostic processes. The ARD and CFS groups showed similarities but also key differences in their responses to symptoms. Specific aspects of treatment may need to be tailored towards each group. For example, lack of acceptance and avoidance behaviour may be particularly important in perpetuating fatigue in CFS.

Factors determining fatigue in the chronic fatigue syndrome: a path analysis

Objectives: To explore the interrelationship of different dimensions (fatigue, neuroticism, sleep quality, global mental and physical health) in patients with chronic fatigue syndrome (CFS).Methods: Patients meeting the Fukuda criteria of CFS filled out two independent fatigue scales (Fatigue Questionnaire, FQ and Checklist Individual Strength, CIS), NEO-Five Factor Inventory (NEO-FFI), Pittsburgh Sleep Quality Index (PSQI) and Medical Outcomes Study 36-item Short Form Health Survey (SF36). Exploratory and confirmatory path analyses were performed.Results: Out of 226 eligible patients, 167 subjects were included (mean age 39.13 years, SD 10.14, 92% female). In a first exploratory path analysis, using FQ for assessment of fatigue, night-time PSQI sleep quality had a direct effect on SF36 physical quality of life (PQoL) and no effect on FQ fatigue. This was confirmed by a subsequent path analysis with CIS fatigue and by confirmatory path analyses in 81 patients. These unexpected results raised the question whether FQ or CIS fatigue sufficiently operationalizes fatigue in CFS patients.Conclusions: Poor sleep quality seems to directly impact on mental quality of life (MQoL) and PQoL without mediation of fatigue assessed with FQ and CIS. A more cohesive framework needs to be developed with more comprehensive clinical tools for the different dimensions in the construct of CFS.

Subjective but Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study

This study aimed to (1) examine the relationship between subjective and actigraphy-defined sleep, and next-day fatigue in chronic fatigue syndrome (CFS); and (2) investigate the potential mediating role of negative mood on this relationship. We also sought to examine the effect of presleep arousal on perceptions of sleep. Twenty-seven adults meeting the Oxford criteria for CFS and self-identifying as experiencing sleep difficulties were recruited to take part in a prospective daily diary study, enabling symptom capture in real time over a 6-day period. A paper diary was used to record nightly subjective sleep and presleep arousal. Mood and fatigue symptoms were rated four times each day. Actigraphy was employed to provide objective estimations of sleep duration and continuity. Multilevel modelling revealed that subjective sleep variables, namely sleep quality, efficiency, and perceiving sleep to be unrefreshing, predicted following-day fatigue levels, with poorer subjective sleep related to increased fatigue. Lower subjective sleep efficiency and perceiving sleep as unrefreshing predicted reduced variance in fatigue across the following day. Negative mood on waking partially mediated these relationships. Increased presleep cognitive and somatic arousal predicted self-reported poor sleep. Actigraphy-defined sleep, however, was not found to predict following-day fatigue. For the first time we show that nightly subjective sleep predicts next-day fatigue in CFS and identify important factors driving this relationship. Our data suggest that sleep specific interventions, targeting presleep arousal, perceptions of sleep and negative mood on waking, may improve fatigue in CFS.

Acupuncture for chronic fatigue syndrome and idiopathic chronic fatigue: a multicenter, nonblinded, randomized controlled trial.

BackgroundThe causes of chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) are not clearly known, and there are no definitive treatments for them. Therefore, patients with CFS and ICF are interested in Oriental medicine or complementary and alternative medicine. For this reason, the effectiveness of complementary and alternative treatments should be verified. We investigated the effectiveness of two forms of acupuncture added to usual care for CFS and ICF compared to usual care alone.MethodsA three-arm parallel, non-blinded, randomized controlled trial was performed in four hospitals. We divided 150 participants into treatment and control groups at the same ratio. The treatment groups (Group A, body acupuncture; Group B, Sa-am acupuncture) received 10 sessions for 4 weeks. The control group (Group C) continued usual care alone. The primary outcome was the Fatigue Severity Scale (FSS) at 5 weeks after randomization. Secondary outcomes were the FSS at 13 weeks and a short form of the Stress Response Inventory (SRI), the Beck Depression Inventory (BDI), the Numeric Rating Scale (NRS), and the EuroQol-5 Dimension (EQ-5D) at 5 and 13 weeks.ResultsGroup A showed significantly lower FSS scores than Group C at 5 weeks (P = 0.023). SRI scores were significantly lower in the treatment groups than in the control group at 5 (Group A, P = 0.032; B, P <0.001) and 13 weeks (Group A, P = 0.037; B, P <0.001). Group B showed significantly lower BDI scores than Group C at 13 weeks (P = 0.007). NRS scores from the treatment groups were significantly reduced compared to control at 5 (Group A and B, P <0.001) and 13 weeks (Group A, P = 0.011; B, P = 0.002).ConclusionsBody acupuncture for 4 weeks in addition to usual care may help improve fatigue in CFS and ICF patients.Trial registrationClinical Research Information Service (CRIS) KCT0000508; Registered on 12 August 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0857-0) contains supplementary material, which is available to authorized users.

Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome – A randomized, controlled, double-blind trial

Chronic Fatigue Syndrome (CFS) is a complex condition, characterized by severe disabling fatigue with no known cause, no established diagnostic tests, and no universally effective treatment. Several studies have proposed symptomatic treatment with coenzyme Q10 (CoQ10) and nicotinamide adenine dinucleotide (NADH) supplementation. The primary endpoint was to assess the effect of CoQ10 plus NADH supplementation on age-predicted maximum heart rate (max HR) during a cycle ergometer test. Secondary measures included fatigue, pain and sleep. A proof-of-concept, 8-week, randomized, controlled, double-blind trial was conducted in 80 CFS patients assigned to receive either CoQ10 plus NADH supplementation or matching placebo twice daily. Maximum HR was evaluated at baseline and at end of the run-in period using an exercise test. Fatigue, pain and sleep were evaluated at baseline, and then reassessed at 4- and 8-weeks through self-reported questionnaires. The CoQ10 plus NADH group showed a significant reduction in max HR during a cycle ergometer test at week 8 versus baseline (P=0.022). Perception of fatigue also showed a decrease through all follow-up visits in active group versus placebo (P=0.03). However, pain and sleep did not improve in the active group. Coenzyme Q10 plus NADH was generally safe and well tolerated. Our results suggest that CoQ10 plus NADH supplementation for 8 weeks is safe and potentially effective in reducing max HR during a cycle ergometer test and also on fatigue in CFS. Further additional larger controlled trials are needed to confirm these findings. Clinical trial registrationThis trial was registered at clinicaltrials.gov as NCT02063126.

Investigating neural mechanisms of change of cognitive behavioural therapy for chronic fatigue syndrome: a randomized controlled trial

BackgroundChronic fatigue syndrome (CFS) is characterized by profound and disabling fatigue with no known somatic explanation. Cognitive behavioral therapy (CBT) has proven to be a successful intervention leading to a reduction in fatigue and disability. Based on previous neuroimaging findings, it has been suggested that central neural mechanisms may underlie CFS symptoms and play a role in the change brought on by CBT. In this randomized controlled trial we aim to further investigate the neural mechanisms that underlie fatigue in CFS and their change by CBT.Methods/DesignWe will conduct a randomized controlled trial in which we collect anatomical and functional magnetic resonance imaging (MRI) measures from female CFS patients before and after CBT (N = 60) or waiting list (N = 30) and compare these with measures from age and education matched healthy controls (N = 30). By including a large treatment group we will also be able to compare patients that benefit from CBT with those that do not. In addition, to further investigate the role of endocrine and immune biomarkers in CFS, we will determine cortisol and cytokine concentrations in blood, hair and/or saliva.DiscussionThis project creates an unique opportunity to enhance our understanding of CFS symptoms and its change by CBT in terms of neuroanatomical, neurofunctional, endocrinological and immunological mechanisms and can help to further improve future treatments strategies.Trial registrationDutch Trial Register #15852. Registered 9 December 2013 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4311)

The Metacognitions about Symptoms Control Scale: Development and Concurrent Validity.

This paper presents the development and preliminary validation of a self-report instrument designed to measure metacognitions pertaining to symptoms control in the form of the following: (1) symptoms focusing and (2) symptoms conceptual thinking. A total of 124 patients (95 female and 29 male) presenting with chronic fatigue syndrome (CFS) contributed data to the study to test the structure and psychometric properties of the Metacognitions about Symptoms Control Scale (MaSCS). A principal components factor analysis indicated that a two-factor solution best fitted the data. The factors were labelled positive and negative metacognitions about symptoms control. Further analyses revealed that both factors had good internal consistency. Correlation analyses established preliminary concurrent validity, indicating that both positive and negative metacognitions about symptoms control were significantly associated with levels of fatigue in CFS. Regression analysis revealed that positive and negative metacognitions about symptoms control significantly predicted fatigue severity when controlling for anxiety and depression. The newly developed instrument may help future research that examines the role of metacognitions in CFS, as well as aiding clinical assessment and case formulation. The MaSCS is a useful first instrument to assess metacognitions in CFS. The MaSCS may help to deepen our understanding of symptoms control (symptoms focusing and conceptual thinking about symptoms) in the experience of CFS symptoms. Assessing and conceptualizing symptoms control through the MaSCS may aid treatment of CFS.

Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes

Several studies recognized an overlap between CFS (chronic fatigue syndrome) and POTS (postural tachycardia syndrome). We compared the autonomic and neurohormonal phenotype of POTS patients with CFS (CFS–POTS) to those without CFS (non-CFS–POTS), to determine whether CFS–POTS represents a unique clinical entity with a distinct pathophysiology. We recruited 58 patients with POTS, of which 47 were eligible to participate. A total of 93% of them reported severe fatigue [CIS (Checklist of Individual Strength), fatigue subscale >36], and 64% (n=30) fulfilled criteria for CFS (CFS–POTS). The prevalence of CFS symptoms (Centers for Disease Control and Prevention criteria) was greater in the CFS–POTS group, but the pattern of symptoms was similar in both groups. Physical functioning was low in both groups (RAND-36 Health Survey, 40±4 compared with 33±3; P=0.153), despite more severe fatigue in CFS–POTS patients (CIS fatigue subscale 51±1 compared with 43±3; P=0.016). CFS–POTS patients had greater orthostatic tachycardia than the non-CFS–POTS group (51±3 compared with 40±4 beats/min; P=0.030), greater low-frequency variability of BP (blood pressure; 6.3±0.7 compared with 4.8±1.0 mmHg2; P=0.019), greater BP recovery from early to late phase II of the Valsalva manoeuvre (18±3 compared with 11±2 mmHg; P=0.041) and a higher supine (1.5±0.2 compared with 1.0±0.3 ng/ml per·h; P=0.033) and upright (5.4±0.6 compared with 3.5±0.8 ng/ml per h; P=0.032) PRA (plasma renin activity). In conclusion, fatigue and CFS-defining symptoms are common in POTS patients. The majority of them met criteria for CFS. CFS–POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients.

Cognitive impairment in fatigue and sleepiness associated conditions

Although relating to very different concepts, sleepiness and fatigue are often confounded. However, both fatigue–associated conditions such as the chronic fatigue syndrome (CFS) and sleepiness–associated conditions such as the sleep apnea–hypopnea syndrome (SAHS) are associated with cognitive impairment with impaired attention, concentration and memory performances. Fifteen pure CFS patients, without primary sleep disorders or clinically relevant sleepiness, were compared to 15 untreated SAHS patients, without clinically relevant fatigue, and to 16 healthy controls of similar age. The auditory verbal learning test (AVLT), digit span, digit symbol and finger tapping test (FTT) were used as cognitive and behavioural measures. In addition we assessed daytime EEG spectral power and P300 evoked potentials. With exception for the digit span, all tests showed lower performances in patient groups. Recall on the AVLT did not differ between the two patient groups, but the digit and symbol spans showed more severe impairment in SAHS patients. Psychomotor performance on the FTT presented with slower hit rates in SAHS than in CFS. EEG theta power was highest in CFS patients. P300 latencies and amplitudes did not differ between groups. Fatigue– and sleepiness–associated conditions can both present with significant and objective impairment of cognitive functioning and behavioural motor performance. In our sample cognitive impairment and psychomotor performance were worse when associated to sleepiness in SAHS than with fatigue in CFS.

Predictors of outcome in a multi-component treatment program for chronic fatigue syndrome

Background Little is known about factors predicting treatment outcome in chronic fatigue syndrome (CFS). Methods Based on Vercoulen et al.'s (1998) cognitive–behavioral model of perpetuating factors in CFS, the predictive value of the following patient characteristics were examined in a sample of 178 CFS patients who followed a multi-component treatment program: (1) somatic attributions, (2) psychological attributions, (3) sense of control over symptoms, (4) physical activity, (5) functional impairment, (6) somatic focus, and (7) severity of depression. Results Only pre-treatment severity of depression was associated with negative treatment outcome defined in terms of post-treatment fatigue and improvement in fatigue. Limitations The study was conducted at a tertiary care centre and did not include a control group or a long-term follow-up. Conclusions Level of depression may be the most important factor of the cognitive–behavioral model predicting post-treatment fatigue in CFS. Hence, findings suggest that treatment of CFS should include a focus on severity of depression.

How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity

Cognitive behaviour therapy (CBT) is known to reduce fatigue severity in chronic fatigue syndrome (CFS). How this change in symptomatology is accomplished is not yet understood. The purpose of the present study was to determine whether the effect of CBT on fatigue is mediated by an increase in physical activity. Three randomized controlled trials were reanalysed, previously conducted to evaluate the efficacy of CBT for CFS. In all samples, actigraphy was used to assess the level of physical activity prior and subsequent to treatment or a control group period. The mediation hypothesis was analysed according to guidelines of Baron & Kenny [Journal of Personality and Social Psychology (1986)51, 1173-1182]. A non-parametric bootstrap approach was used to test statistical significance of the mediation effect. Although CBT effectively reduced fatigue, it did not change the level of physical activity. Furthermore, changes in physical activity were not related to changes in fatigue. Across the samples, the mean mediation effect of physical activity averaged about 1% of the total treatment effect. This effect did not yield significance in any of the samples. The effect of CBT on fatigue in CFS is not mediated by a persistent increase in physical activity.

Possible use of repeated cold stress for reducing fatigue in chronic fatigue syndrome: a hypothesis

BackgroundPhysiological fatigue can be defined as a reduction in the force output and/or energy-generating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity. A typical example of a fatigue-related disorder is chronic fatigue syndrome (CFS), a disabling condition of unknown etiology and with uncertain therapeutic options. Recent advances in elucidating pathophysiology of this disorder revealed hypofunction of the hypothalamic-pituitary-adrenal axis and that fatigue in CFS patients appears to be associated with reduced motor neurotransmission in the central nervous system (CNS) and to a smaller extent with increased fatigability of skeletal muscle. There is also some limited evidence that CFS patients may have excessive serotonergic activity in the brain and low opioid tone.Presentation of the hypothesisThis work hypothesizes that repeated cold stress may reduce fatigue in CFS because brief exposure to cold may transiently reverse some physiological changes associated with this illness. For example, exposure to cold can activate components of the reticular activating system such as raphe nuclei and locus ceruleus, which can result in activation of behavior and increased capacity of the CNS to recruit motoneurons. Cold stress has also been shown to reduce the level of serotonin in most regions of the brain (except brainstem), which would be consistent with reduced fatigue according to animal models of exercise-related fatigue. Finally, exposure to cold increases metabolic rate and transiently activates the hypothalamic-pituitary-adrenal axis as evidenced by a temporary increase in the plasma levels of adrenocorticotropic hormone, beta-endorphin and a modest increase in cortisol. The increased opioid tone and high metabolic rate could diminish fatigue by reducing muscle pain and accelerating recovery of fatigued muscle, respectively.Testing the hypothesisTo test the hypothesis, a treatment is proposed that consists of adapted cold showers (20 degrees Celsius, 3 minutes, preceded by a 5-minute gradual adaptation to make the procedure more comfortable) used twice daily.Implications of the hypothesisIf testing supports the proposed hypothesis, this could advance our understanding of the mechanisms of fatigue in CFS.

Body Mass Index and Fatigue Severity in Chronic Fatigue Syndrome

AbstractBackground: It is uncertain how much fatigue is related to weight in patients with chronic fatigue syndrome (CFS).Objective: To assess the association of body mass index (BMI) and fatigue in CFS patients.Methods: Consecutive patients seen in a referral-based specialty clinic were eligible if they met CFS criteria and had completed required measures. Fatigue measures were the vitality subscale of the Medical Outcomes Short-Form 36 and the global fatigue index from the Multidimensional Assessment of Fatigue.Results: In women, there was no relationship between BMI and vitality subscale or global fatigue index scores (P = 0.99 and P = 0.44). For men, vitality subscale scores significantly decreased as BMI increased (P = 0.02).Conclusions: In CFS patients, the prevalence of obesity was low despite risk factors for weight gain. Fatigue severity and BMI were unrelated in women with CFS, but this relationship may differ for men.

A placebo-controlled, double-blind, randomized controlled trial of a natural killer cell stimulant (BioBran MGN-3) in chronic fatigue syndrome

Previous research has suggested that natural killer (NK) cell activity may be reduced in patients with chronic fatigue syndrome (CFS). To evaluate the effectiveness of a putative NK cell stimulant, BioBran MGN-3, in reducing fatigue in CFS patients. Randomized, double-blind, placebo-controlled trial. We recruited 71 patients with CFS (according to the Centers for Disease Control 1994 criteria) attending an out-patient specialist CFS service. Participants were given oral BioBran MGN-3 for 8 weeks (2 g three times per day) or placebo equivalent. The primary outcome measure was the Chalder physical fatigue score. Self-reported fatigue measures, self-assessment of improvement, change in key symptoms, quality of life, anxiety and depression measures were also included. Data were complete in 64/71 patients. Both groups showed marked improvement over the study duration, but without significant differences. Mean improvement in the Chalder fatigue score (physical scale) was 0.3 (95%CI -2.6 to 3.2) lower in the BioBran group. The findings do not support a specific therapeutic effect for BioBran in CFS. The improvement showed by both groups over time highlights the importance of placebo controls when evaluating interventions in CFS.

Reliability of physiological, psychological, and cognitive variables in chronic fatigue syndrome

The purpose of this study was to assess the reliability of specific physiological, psychological, and cognitive variables in 31 chronic fatigue syndrome (CFS) subjects and 31 matched control subjects. All variables were assessed weekly over a 4-week period and reliability was determined using an intraclass correlation coefficient (ICC). Results ranged from moderately to highly reliable for all variables assessed, except for mental and physical fatigue, which were of questionable reliability in both groups (ICC = 0.61 and 0.65, respectively, for the CFS group; 0.62 and 0.52 for the control group). A Pearson product-moment correlation analysis that compared exercise performance with all psychological variables assessed, demonstrated a significant relationship between exercise performance and depression (r = .41, P = .02) in week 3 only, suggesting minimal association between objective performance and psychological responses. These correlation results support a central, as opposed to a peripheral, basis to the sensation of fatigue in CFS.

Levels of DHEA and DHEAS and responses to CRH stimulation and hydrocortisone treatment in chronic fatigue syndrome

Background: An association between chronic fatigue syndrome (CFS) and abnormalities of the hypothalamo-pituitary–adrenal axis has been described, and other adrenal steroid abnormalities have been suggested. Dehydroepiandrostenedione (DHEA) and its sulphate (DHEA-S), apart from being a precursor of sex steroids, have other functions associated with memory, depression and sleep. It has been suggested that CFS may be associated with a state of relative DHEA(-S) deficiency. Therefore we investigated basal levels of DHEA(-S), the cortisol/DHEA molar ratio and the responsiveness of DHEA to stimulation by corticotrophin-releasing hormone (CRH). Recent studies have also suggested that low dose hydrocortisone may be effective at reducing fatigue in CFS. We therefore also assessed these parameters prior to and following treatment with low dose oral hydrocortisone. Methods: Basal levels of serum DHEA, DHEAS and cortisol were measured in 16 patients with CFS without depression and in 16 controls matched for age, gender, weight, body mass index and menstrual history. CRH tests (1 μg/kg IV) were carried out on all subjects and DHEA measured at 0, +30 and +90 min. In the patient group, CRH tests were repeated on two further occasions following treatment with hydrocortisone (5 or 10 mg, PO) or placebo for 1 month each in a double-blind cross over study protocol. Results: Basal levels of DHEA were higher in the patient, compared to the control, group (14.1±2.2 vs. 9.0±0.90 ng/ml, P=0.04), while levels of DHEAS in patients (288.7±35.4 μg/dl) were not different from controls (293.7±53.8, P=NS). Higher DHEA levels were correlated with higher disability scores. Basal cortisol levels were higher in patients, and consequently the cortisol/DHEA molar ratio did not differ between patients and controls. Levels of DHEA (8.9±0.97 ng/ml, P=0.015) and DHEAS (233.4±41.6 μg/dl, P=0.03) were lower in patients following treatment with hydrocortisone. There was a rise in DHEA responsiveness to CRH in the patients after treatment but this did not attain significance (AUC c: 2.5±1.7 ng/ml h pre-treatment vs. 6.4±1.2 ng/ml h post-hydrocortisone, P=0.053). However, those patients who responded fully to hydrocortisone in terms of reduced fatigue scores did show a significantly increased DHEA responsiveness to CRH (AUC c: −1.4±2.5 ng/ml h at baseline, 5.0±1.2 ng/ml h after active treatment, P=0.029). Conclusions: DHEA levels are raised in CFS and correlate with the degree of self-reported disability. Hydrocortisone therapy leads to a reduction in these levels towards normal, and an increased DHEA response to CRH, most marked in those who show a clinical response to this therapy.

Integrity of the growth hormone/insulin-like growth factor system is maintained in patients with chronic fatigue syndrome.

GH deficiency states and chronic fatigue syndrome (CFS) share several characteristics, and preliminary studies have revealed aspects of GH dysfunction in CFS. This study assessed indexes of GH function in 37 medication-free CFS patients without comorbid psychiatric illness and 37 matched healthy controls. We also assessed GH function before and after treatment with low dose hydrocortisone, which has been shown recently to reduce fatigue in CFS. We measured basal levels of serum insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2 and IGFBP-3 together with 24-h urinary GH excretion. We also performed 2 dynamic tests of GH function: a 100-microg GHRH test and an insulin stress test using 0.15 U/kg BW insulin. There were no differences between patients and controls in basal levels of IGF/IGFBP or in urinary GH excretion. GH responses to both the GHRH test and the insulin stress test were no different in patients and controls. CFS patients did have a marginally reduced suppression of IGFBP-1 during the insulin stress test. Hydrocortisone treatment had no significant effect on any of these parameters. There is no evidence of GH deficiency in CFS. At the doses used, hydrocortisone treatment appears to have little impact on GH function.

Chronic fatigue syndrome is an acquired neurological channelopathy

Many symptoms of chronic fatigue syndrome (CFS), including severity of fatigue, may be periodic, fluctuant and induced by physical and mental activities, including trauma and stress. The fatigue in CFS is distinct from the fatigue of neuromuscular disorders but is similar to that found in disorders of the central nervous system such as multiple sclerosis, Parkinson's disease and multiple system atrophy. Though fatigue is a common symptom of depressive disorders, it is now clear that CFS patients differ from patients with major depression in their symptoms, biologic markers such as steroid metabolism and response to standard antidepressant drug therapy. In this paper, we propose dysfunctional ion channels in the cell membranes as the key abnormality in CFS which may also be responsible for the altered neuroendocrine functions reported in this condition. In our hypothesis, changes in the neuronal ion channel function from time to time offers a rational basis to explain fluctuating fatigue and related symptoms in CFS. Finally, ion channel abnormality leading to selective neuronal instability may be the common disease mechanism in CFS and other paroxysmal disorders affecting brain functions such as migraine and epilepsy. Copyright © 1999 John Wiley & Sons, Ltd.