Integration of gene expression,clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome

Background  

Chronic fatigue syndrome (CFS) has no diagnostic clinical signs or diagnostic laboratory abnormalities and it is unclear if it represents a single illness. The CFS research case definition recommends stratifying subjects by co-morbid conditions, fatigue level and duration, or functional impairment. But to date, this analysis approach has not yielded any further insight into CFS pathogenesis. This study used the integration of peripheral blood gene expression results with epidemiologic and clinical data to determine whether CFS is a single or heterogeneous illness.     

Continuing medical education challenges in chronic fatigue syndrome

Background  

Chronic fatigue syndrome (CFS) affects at least 4 million people in the United States, yet only 16% of people with CFS have received a diagnosis or medical care for their illness. Educating health care professionals about the diagnosis and management of CFS may help to reduce population morbidity associated with CFS.     

A train-the-trainer education and promotion program: chronic fatigue syndrome – a diagnostic and management challenge

Background  

Chronic fatigue syndrome (CFS) is a complicated illness for providers and patients. Fewer than 20% of persons with CFS have been diagnosed and treated. For providers, compounding the issue are the challenges in making a diagnosis due to the lack of a biomedical marker.     

An evaluation of exclusionary medical/psychiatric conditions in the definition of chronic fatigue syndrome

Background  

The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the exclusion of subjects with medical and psychiatric conditions that could confound the analysis and interpretation of results. This study compares illness parameters between individuals with CFS who have and those who do not have exclusionary conditions.     

Prevalence of DSM-IV Personality Disorders in Patients with Chronic Fatigue Syndrome: A Controlled Study

Background

It is not yet clear whether chronic fatigue syndrome (CFS) is associated with elevated levels of personality disorders.

Purpose

This study aims to determine the prevalence of DSM-IV axis II personality disorders among patients with CFS.

Methods

We examined the prevalence of personality disorders in a sample of 92 female CFS patients and in two well-matched control groups, i.e., normal community individuals (N?=?92) and psychiatric patients (N?=?92). Participants completed the assessment of DSM-IV personality disorders questionnaire (ADP-IV), which yields a categorical and dimensional evaluation of personality disorder features.

Results

The prevalence of personality disorders in CFS patients (16.3 %) was significantly lower than in psychiatric patients (58.7 %) and was similar to that in the community sample (16.3 %). Similar results were found for dimensional and pseudodimensional scores, except for the Depressive (DE) and Obsessive–Compulsive Personality Disorder (O-C) subscales. Patients with CFS had significantly higher levels of DE features compared to normal controls and similar dimensional scores on the O-C scale compared to psychiatric controls.

Conclusions

Although the CFS sample was characterized by depressive and obsessive–compulsive personality features, this study provides no evidence for the assumption that these patients generally show a higher prevalence of axis II pathology. Given the conflicting findings in this area, future studies using multiple measures to assess personality disorders in CFS are needed to substantiate these findings.     

Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways

Background  

In a recently published paper, Harvey and Wessely put forward a 'biopsychosocial' explanatory model for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is proposed to be applicable to (chronic) fatigue even when apparent medical causes are present.     

Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity

Background  

The aim of this study was to investigate the possibility that a decreased mitochondrial ATP synthesis causes muscular and mental fatigue and plays a role in the pathophysiology of the chronic fatigue syndrome (CFS/ME).     

Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States

Background  

Chronic fatiguing illnesses, including chronic fatigue syndrome (CFS), pose a diagnostic and therapeutic challenge. Previous clinical reports addressed the utilization of health care provided to patients with CFS by a variety of practitioners with other than allopathic training, but did not examine the spectrum of complementary and alternative medicine (CAM) therapies used. This study was designed to measure CAM therapy use by persons with fatiguing illnesses in the United States population.     

Differences in Physical and Psychosocial Characteristics Between CFS and Fatigued Non-CFS Patients,a Case-Control Study

Purpose

The main research question is: “Do CFS patients differ from fatigued non-CFS patients with respect to physical, cognitive, behavioral, social, and emotional determinants?” In addition, group differences in relevant outcomes were explored.

Method

Patients who met the Centers for Disease Control (CDC) criteria for CFS were categorized as CFS; these patients were mainly recruited via a large Dutch patient organization. Primary care patients who were fatigued for at least 1 month and up to 2 years but did not meet the CDC criteria were classified as fatigued non-CFS patients. Both groups were matched by age and gender (N?=?192 for each group).

Results

CFS patients attributed their fatigue more frequently to external causes, reported a worse physical functioning, more medical visits, and a lower employment rate. The results of a multiple logistic regression analysis showed that patients who believe that their fatigue is associated with more severe consequences, that their fatigue will last longer and is responsible for more additional symptoms are more likely to be classified as CFS, while patients who are more physically active and have higher levels of “all or nothing behavior” are less likely to be classified as having CFS.

Conclusion

A longitudinal study should explore the predictive value of the above factors for the transition from medically unexplained fatigue to CFS in order to develop targeted interventions for primary care patients with short-term fatigue complaints.

     

A Cross-Cultural Perspective on Psychological Determinants of Chronic Fatigue Syndrome: a Comparison Between a Portuguese and a Dutch Patient Sample

Background

Few studies focus on cross-cultural differences in Chronic fatigue syndrome (CFS).

Purpose

This study aimed to (1) compare fatigue severity and impairment, somatic complaints, psychological distress, and quality of life (QoL) in a population of Portuguese and Dutch patients; (2) explore the differential contribution of behavioral and cognitive determinants of fatigue severity; and (3) investigate the relation between fatigue severity and somatic complaints on one hand and QoL on the other in both populations.

Method

Eighty-five female patients from Portugal (Mean age?=?47.54) and 167 female CFS patients from The Netherlands (Mean age?=?44.93) participated in the study. All participants were surveyed for demographic and clinical characteristics, fatigue severity, somatic symptoms, psychological distress, (physical and psychological) QoL, physical activity, behavior regulation patterns, and illness representations.

Results

Cross-cultural differences were found in relation to working status, duration of fatigue symptoms, psychological distress, somatic complaints, and psychological QoL. Although behavioral characteristics and illness representations were significantly associated with fatigue severity in both Portuguese and Dutch patients, there were important differences in the determinants of CFS. Moreover, higher levels of fatigue and severity of other somatic complaints were related to poor QoL.

Conclusions

These findings show cross-cultural similarities and differences in clinical characteristics and psychological determinants of CFS that are important in view of diagnosis and treatment.     

Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study

Background

The lack of standardized criteria for defining chronic fatigue syndrome (CFS) has constrained research. The objective of this study was to apply the 1994 CFS criteria by standardized reproducible criteria.

Methods

This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n = 28). Participants were admitted to a hospital for two days and underwent medical history and physical examination, the Diagnostic Interview Schedule, and laboratory testing to identify medical and psychiatric conditions exclusionary for CFS. Illness classification at the time of the clinical study utilized two algorithms: (1) the same criteria as in the surveillance study; (2) a standardized clinically empirical algorithm based on quantitative assessment of the major domains of CFS (impairment, fatigue, and accompanying symptoms).

Results

One hundred and sixty-four participants had no exclusionary conditions at the time of this study. Clinically empirical classification identified 43 subjects as CFS, 57 as ISF, and 64 as not ill. There was minimal association between the empirical classification and classification by the surveillance criteria. Subjects empirically classified as CFS had significantly worse impairment (evaluated by the SF-36), more severe fatigue (documented by the multidimensional fatigue inventory), more frequent and severe accompanying symptoms than those with ISF, who in turn had significantly worse scores than the not ill; this was not true for classification by the surveillance algorithm.

Conclusion

The empirical definition includes all aspects of CFS specified in the 1994 case definition and identifies persons with CFS in a precise manner that can be readily reproduced by both investigators and clinicians.     

A comparison of classification methods for predicting Chronic Fatigue Syndrome based on genetic data

Background  

In the studies of genomics, it is essential to select a small number of genes that are more significant than the others for the association studies of disease susceptibility. In this work, our goal was to compare computational tools with and without feature selection for predicting chronic fatigue syndrome (CFS) using genetic factors such as single nucleotide polymorphisms (SNPs).     

The role of depression in pain, psychophysiological syndromes and medically unexplained symptoms associated with chronic fatigue syndrome

BACKGROUND: The association between depression and pain, function, medically unexplained symptoms and psychophysiological syndromes such as irritable bowel syndrome has not been explored before in chronic fatigue syndrome. METHODS: Cross-sectional controlled study of the current prevalence of psychophysiological syndromes, pain, function and lifetime prevalence of medically unexplained symptoms in 77 out-patients with chronic fatigue syndrome (CFS) without DSM-III-R depression, 42 CFS out-patients with DSM-III-R depression and 26 out-patient with primary DSM-III-R depression. RESULTS: Both CFS groups differed significantly from the primary depression group but not each other in the prevalence of tension headaches (P < 0.001), reporting of widespread bodily pain (P < 0.001) and the number of lifetime medically unexplained symptoms (P < 0.001). The three groups did not significantly differ in the prevalence of irritable bowel syndrome or fibromyalgia. CFS patients with depression were more impaired in social function than other CFS patients. CONCLUSION: Depression is not associated with the reporting of pain, psychophysiological syndromes and medically unexplained symptoms in CFS patients. Depression is associated with decreased social function in CFS patients. LIMITATIONS: Study depended on recall of symptoms, not confirmed by medical records and current investigations. Patients with depression were taking antidepressants. CLINICAL RELEVANCE: Treating depression in chronic fatigue syndrome is unlikely to diminish reporting of pain and medically unexplained symptoms but may improve social function.     

Self-investigation in adolescent chronic fatigue syndrome: Narrative changes and health improvement

Objective

A small-scale intervention study into narrative self-investigation in adolescent chronic fatigue syndrome (CFS).

Method

The self-confrontation method (SCM) is an instrument to assess and change personal life stories. Forty-two adolescents diagnosed with CFS were included and randomly assigned to either 6 or 12 sessions with the SCM. Twenty-five healthy adolescents were assigned to 6 sessions. Outcome was measured directly after the self-investigation procedure at 4 months. Follow-up measurements were made 10 months later. The Checklist Individual Strength and the Child Health Questionnaire were used to measure changes in fatigue, physical and psychosocial functioning.

Results

Self-investigation resulted in significant changes in participants’ narratives. Moreover, after self-investigation there was a significant improvement in fatigue, physical and psychosocial functioning for the adolescents with CFS. The patients who completed 12 sessions improved most. At follow-up, the positive effects were maintained.

Conclusion

Self-investigation enables a move beyond the symptoms of CFS in an individualized, patient centered way. Narrative transformation seems to contribute to improved physical and psychosocial outcome in adolescent CFS.

Practice implications

The SCM allows adolescents to discover (for themselves) factors that might cause or perpetuate their fatigue. The results suggest that self-investigation is a useful instrument in the management of adolescent CFS.     

Lipid and protein oxidation in female patients with chronic fatigue syndrome

Introduction

Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS.

Material and methods

Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined.

Results

The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol.

Conclusions

The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.     

Dimensions of pure chronic fatigue: psychophysical,cognitive and biological correlates in the chronic fatigue syndrome

Objectives

To investigate associated dimensions of fatigue regarding cognitive impairment, psychomotor performances, muscular effort power and circulating cytokine levels and their relations to symptom intensity in a sample of pure chronic fatigue syndrome (CFS) patients without overlapping objective sleepiness or sleep disorders.

Methods

16 CFS patients were compared to 14 matched controls. We assessed structured symptom-scales, polysomnography, multiple sleep latency tests, attention (Zazzo-Cancellation ZCT, digit-symbol-substitution DSST), psychomotor vigilance and speed (PVT, finger tapping test, FTT), dynamometer handgrip force (tonic and phasic trials) and circulating cytokines (IFN-γ, IL-1b, IL-6, IL-8, IL-10, TNF-α).

Results

In addition to fatigue, CFS patients presented with higher affective symptom intensity and worse perceived sleep quality. Polysomnography showed more slow-wave sleep and microarousals in CFS but similar sleep time, efficiency and light-sleep durations than controls. Patients presented with impaired attention (DSST, ZCT), slower reaction times (PVT) but not with lower hit rates (FTT). Notwithstanding lower grip strength during tonic and phasic trials, CFS also presented with higher fatigability during phasic trials. Cytokine levels were increased for IL-1b, IL-8, IL-10 and TNF-α and fatigue intensity was correlated to grip strength and IL-8.

Conclusions

In contrast to sleepiness, chronic fatigue is a more complex phenomenon that cannot be reduced to one single measured dimension (i.e., sleep propensity). Showing its relations to different measurements, our study reflects this multidimensionality, in a psychosomatic disorder such as CFS. To obtain objective information, routine assessments of fatigue should rule out sleepiness, combine aspects of mental and physical fatigue and focus on fatigability.     

In myalgic encephalomyelitis/chronic fatigue syndrome,increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation.

Methods

We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale).

Results

The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise.

Discussion

The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder.     

Influence of Symptom Expectancies on Stair-Climbing Performance in Chronic Fatigue Syndrome: Effect of Study Context

Background

In patients with chronic fatigue syndrome (CFS), performance of physical activities may be affected by an anticipated increase in symptoms after these activities. Nijs et al. previously studied the influence of symptom expectancies and related psychological processes on the performance of an isolated physical activity [Nijs J, Meeus M, Heins M, Knoop H, Moorkens G, Bleijenberg G. Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study. Disabil Rehabil 2012. doi:10.3109/09638288.2011.641661.].

Purpose

We aimed to validate the previous findings in a larger group of patients in a different setting. We also extended the possible underlying psychological processes studied.

Method

In 49 CFS patients, we measured performance (duration and increase in heart rate) during self-paced climbing and descending of two floors of stairs. Before this task, patients rated experienced fatigue and anticipated fatigue after stair climbing. In addition, kinesiophobia, catastrophising and focusing on bodily symptoms were measured. Using correlational and regression analyses, we tested whether performance during stair climbing could be explained by experienced and anticipated fatigue and psychological factors.

Results

Longer duration of stair climbing correlated with higher anticipated fatigue, independently of sex, age, body mass index and fatigue before stair climbing. Focusing on bodily symptoms and fatigue-related catastrophising were related to anticipated fatigue.

Conclusion

Symptom expectations affect the performance of physical activity in CFS patients, possibly through focusing on bodily symptoms and catastrophising. These findings partially contradict the findings of the previous study, which stresses the importance of study context in conducting this type of experiments (i.e., patient characteristics, instructions).     

Immune and hemorheological changes in Chronic Fatigue Syndrome

Background  

Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients.     

Cross-Cultural Study of Information Processing Biases in Chronic Fatigue Syndrome: Comparison of Dutch and UK Chronic Fatigue Patients

Purpose

This study aims to replicate a UK study, with a Dutch sample to explore whether attention and interpretation biases and general attentional control deficits in chronic fatigue syndrome (CFS) are similar across populations and cultures.

Method

Thirty eight Dutch CFS participants were compared to 52 CFS and 51 healthy participants recruited from the UK. Participants completed self-report measures of symptoms, functioning, and mood, as well as three experimental tasks (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) versus neutral words, (ii) interpretive bias task measuring positive versus somatic interpretations of ambiguous information, and (iii) the Attention Network Test measuring general attentional control.

Results

Compared to controls, Dutch and UK participants with CFS showed a significant attentional bias for illness-related words and were significantly more likely to interpret ambiguous information in a somatic way. These effects were not moderated by attentional control. There were no significant differences between the Dutch and UK CFS groups on attentional bias, interpretation bias, or attentional control scores.

Conclusion

This study replicated the main findings of the UK study, with a Dutch CFS population, indicating that across these two cultures, people with CFS demonstrate biases in how somatic information is attended to and interpreted. These illness-specific biases appear to be unrelated to general attentional control deficits.