Tag: chronic fatigue

Gene expression correlates of unexplained fatigue

Abstract:

Quantitative trait analysis (QTA) can be used to test whether the expression of a particular gene significantly correlates with some ordinal variable. To limit the number of false discoveries in the gene list, a multivariate permutation test can also be performed. The purpose of this study is to identify peripheral blood gene expression correlates of fatigue using quantitative trait analysis on gene expression data from 20,000 genes and fatigue traits measured using the multidimensional fatigue inventory (MFI).

A total of 839 genes were statistically associated with fatigue measures. These mapped to biological pathways such as oxidative phosphorylation, gluconeogenesis, lipid metabolism, and several signal transduction pathways. However, more than 50% are not functionally annotated or associated with identified pathways. There is some overlap with genes implicated in other studies using differential gene expression. However, QTA allows detection of alterations that may not reach statistical significance in class comparison analyses, but which could contribute to disease pathophysiology.

This study supports the use of phenotypic measures of chronic fatigue syndrome (CFS) and QTA as important for additional studies of this complex illness. Gene expression correlates of other phenotypic measures in the CFS Computational Challenge (C3) data set could be useful. Future studies of CFS should include as many precise measures of disease phenotype as is practical.

 

Source: Whistler T, Taylor R, Craddock RC, Broderick G, Klimas N, Unger ER. Gene expression correlates of unexplained fatigue. Pharmacogenomics. 2006 Apr;7(3):395-405. https://www.ncbi.nlm.nih.gov/pubmed/16610950

 

The validity of an empirical delineation of heterogeneity in chronic unexplained fatigue

Abstract:

OBJECTIVES: To validate a latent class structure derived empirically from a clinical data set obtained from persons with chronic medically unexplained fatigue.

METHODS: The strategies utilized in this validation study included: recalculating latent class analysis (LCA) results varying random seeds and the number of initial random starting sets; recalculating LCA results by substituting alternate variables to demonstrate a robust solution; determining the statistical significance of between-class differences on disability, fatigue and demographic measures omitted from the data set used for LCA; cross-classifying class membership using established Centers for Disease Control and Prevention (CDC) research criteria for chronic fatigue syndrome (CFS) to compare the relative proportions of subjects designated CFS, chronic fatigue (not CFS) or healthy controls captured by the latent classes.

RESULTS: Recalculation of results and substitution of variables for low-loading variables demonstrated a robust LCA result. Highly significant between-class differences were confirmed between Class 2 (well) and those interpreted as ill/fatigued. Analysis of between-class differences for the fatigue groups revealed significant differences for all disability and fatigue variables, but with equivalent levels of reported activity and reduction in motivation. Cross-classification against established CDC criteria demonstrated that 89% of subjects constituting Class 2 (well) were indeed nonfatigued controls. A general tendency for grouping CFS cases in the multiple symptomatic classes was noted.

CONCLUSION: This study established reasonably good validity for an empirically-derived latent class solution reflecting considerable heterogeneity among subjects with medically unexplained chronic fatigue. This work strengthens the growing understanding of CFS as a heterogeneous entity comprised of several conditions with different underlying pathophysiological mechanisms.

 

Source: Aslakson E, Vollmer-Conna U, White PD. The validity of an empirical delineation of heterogeneity in chronic unexplained fatigue. Pharmacogenomics. 2006 Apr;7(3):365-73. https://www.ncbi.nlm.nih.gov/pubmed/16610947

 

The prevalence of self-reported chronic fatigue in a U.S. twin registry

Abstract:

OBJECTIVE: To investigate the prevalence and correlates of various definitions of self-reported lifetime fatiguing illness in a U.S. twin registry.

METHODS: Data from 4591 female and male twins from the population-based Mid-Atlantic Twin Registry were available for this study. Variables representing different definitions of lifetime fatiguing illness and personal characteristics were obtained through questionnaires. Odds ratios and 95% confidence intervals were calculated as measures of association between fatigue and gender. Kaplan-Meier curves were produced to examine the age at onset for lifetime fatiguing illnesses.

RESULTS: Prevalences for different definitions of self-reported lifetime fatigue ranged from 36.7% for any fatigue to 2.7% for chronic fatigue syndrome-like illness. Females were two to three times more likely to report fatigue than males. Gender differences increased as fatigue definitions grew more restrictive. Ages at onset of chronic fatiguing illness were significantly earlier and the number of ancillary symptoms was greater for females than males. People with lifetime fatigue had significantly more compromised functional status than people without lifetime fatigue.

CONCLUSION: The prevalence of self-reported lifetime fatiguing illness varied widely depending upon how it was defined. Given the debilitating consequences of fatiguing illnesses, the reasons for the female predominance and the earlier onset in women should receive increased research priority.

 

Source: Furberg H, Olarte M, Afari N, Goldberg J, Buchwald D, Sullivan PF. The prevalence of self-reported chronic fatigue in a U.S. twin registry. J Psychosom Res. 2005 Nov;59(5):283-90. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949064/

 

Twin analyses of chronic fatigue in a Swedish national sample

Abstract:

BACKGROUND: Chronic fatigue has infrequently been studied in twins. Data from twin studies can inform clinical and research approaches to the management and etiology of human complex traits.

METHOD: The authors obtained telephone interview data on current chronic fatigue from 31406 individuals twins in the Swedish Twin Registry (aged 42-64 years, 75.68% response rate), from both members of 12407 pairs and from one member of 6592 pairs. Of the complete pairs, 3269 pairs were monozygotic, 9010 pairs dizygotic, and 128 pairs of unknown zygosity. Structural equation twin modeling was used to estimate the latent genetic architecture of varying definitions of fatiguing illness.

RESULTS: Estimates of additive genetic effects, shared environmental effects, and individual-specific environmental effects were similar in males and females. No definition of current fatiguing illness (ranging from any fatigue to CFS-like illness) was strikingly distinctive. Individual-specific effects were the predominant source of variation, followed by modest genetic influences. We could not exclude a small but conceptually important contribution of shared environmental effects.

CONCLUSIONS: Current fatiguing illness appears to be a complex trait resulting from both environmental and genetic sources of variation without pronounced differences by gender.

 

Source: Sullivan PF, Evengård B, Jacks A, Pedersen NL. Twin analyses of chronic fatigue in a Swedish national sample. Psychol Med. 2005 Sep;35(9):1327-36. http://www.ncbi.nlm.nih.gov/pubmed/16168155

 

Predictors of outcome following treatment for chronic fatigue

Abstract:

We explored the role of baseline characteristics of 105 patients who presented with fatigue in primary care in determining outcome following either graded exercise or cognitive-behavioural therapy. Meeting the criteria for chronic fatigue syndrome was the most powerful predictor of poor outcome and this negative effect was enhanced by greater functional impairment or greater perceived negative consequences, but was not further enhanced by both.

 

Source: Darbishire L, Seed P, Ridsdale L. Predictors of outcome following treatment for chronic fatigue. Br J Psychiatry. 2005 Apr;186:350-1. http://bjp.rcpsych.org/content/186/4/350.long (Full article)

 

A systematic review describing the prognosis of chronic fatigue syndrome

Abstract:

AIM: To perform a systematic review of studies describing the prognosis of chronic fatigue (CF) and chronic fatigue syndrome (CFS) and to identify occupational outcomes from such studies.

METHOD: A literature search was used to identify all studies describing the clinical follow-up of patients following a diagnosis of CF or CFS. The prognosis is described in terms of the proportion of individuals improved during the period of follow-up. Return to work, other medical illnesses and death as outcomes are also considered, as are variables which may influence prognosis.

RESULTS: Twenty-eight articles met the inclusion criteria and, for the 14 studies of subjects meeting operational criteria for CFS, the median full recovery rate was 5% (range 0-31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8-63%). Less fatigue severity at baseline, a sense of control over symptoms and not attributing illness to a physical cause were all associated with a good outcome. Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome.

CONCLUSIONS: Full recovery from untreated CFS is rare. The prognosis for an improvement in symptoms is less gloomy. This review looks at the course of CF/CFS without systematic intervention. However, there is increasing evidence for the effectiveness of cognitive behavioural and graded exercise therapies. Medical retirement should be postponed until a trial of such treatment has been given.

 

Source: Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond). 2005 Jan;55(1):20-31. http://occmed.oxfordjournals.org/content/55/1/20.long (Full artricle)

 

Randomized controlled trial of Siberian ginseng for chronic fatigue

Abstract:

BACKGROUND: Chronic fatigue greatly affects quality of life and is a common reason for consulting a physician. Since conventional therapy is often of limited help, fatigued patients may use herbal treatments. This randomized controlled trial evaluated the effectiveness of Siberian ginseng.

METHOD: Subjects were recruited from advertisements in Iowa (82%) and members of chronic fatigue syndrome support groups (18%). Potential subjects were required to have substantial fatigue > or = 6 months with no identifiable cause. The mean change in a fatigue measure was compared for placebo and Siberian ginseng at 1 and 2 months. Comparisons were for all subjects and for subjects with characteristics previously identified in the literature as important for categorizing chronic fatigue.

RESULTS: Ninety-six subjects were randomized to treatment groups, and 76 provided information at 2 months of follow-up. Fatigue among subjects assigned to either placebo or Siberian ginseng was substantially reduced during the study, but differences between treatment groups were not statistically significant in the full sample. Fatigue severity and duration had a statistically significant interaction with response to Siberian ginseng at the P < 0.05 level. Treatment was effective at 2 months for 45 subjects with less severe fatigue (P = 0.04 unadjusted for multiple comparisons) and for 41 subjects with fatigue for > or = 5 years (P = 0.09 unadjusted for multiple comparisons).

CONCLUSION: Overall efficacy was not demonstrated. However, the findings of possible efficacy for patients with moderate fatigue suggests that further research may be of value.

 

Source: Hartz AJ, Bentler S, Noyes R, Hoehns J, Logemann C, Sinift S, Butani Y, Wang W, Brake K, Ernst M, Kautzman H. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol Med. 2004 Jan;34(1):51-61. http://www.ncbi.nlm.nih.gov/pubmed/14971626

 

Chronic fatigue and chronic fatigue syndrome in the general population

Both chronic fatigue (CF) connected to a chronic or serious disease, and Chronic Fatigue Syndrome (CFS) form a serious problem in our Western society. It causes a lot of suffering for patients and may lead to disability to work. Doctors are frequently confronted with these patients, but it is unknown how many of these patients are suffering without help-seeking.

Most research has been done in CFS, and in specialised CFS clinics. Much less is known about other types of chronic fatigue, connected with a serious disabling disease, or with a psychiatric condition. There is hardly any knowledge about the prevalence and characteristics of these types of chronic fatigue and especially CFS, and the course of CFS in the general population. If we would know more about fatigue and chronic fatigue in the general population then, for example, the development of prevention programs would become nearer.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269992/

 

Comment on:

Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population. [Health Qual Life Outcomes. 2003]

A population-based study of the clinical course of chronic fatigue syndrome. [Health Qual Life Outcomes. 2003]

 

Source: Bleijenberg G. Chronic fatigue and chronic fatigue syndrome in the general population. Health Qual Life Outcomes. 2003 Oct 6;1:52. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269992/ (Full article)

 

Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has been defined, but many more patients consult in primary care with chronic fatigue that does not meet the criteria for CFS. General practitioners (GPs) do not generally use the CFS diagnosis, and have some doubt about the validity of CFS as an illness.

AIM: To describe the proportion of patients consulting their GP for fatigue that met the criteria for CFS, and to describe the social, psychological, and physical differences between patients with CFS and those with non-CFS chronic fatigue in primary care.

DESIGN OF STUDY: Baseline data from a trial of complex interventions for fatigue in primary care.

SETTING: Twenty-two general practices located in London and the South Thames region of the United Kingdom recruited patients to the study between 1999 and 2001.

METHOD: One hundred and forty-one patients who presented to their GP with unexplained fatigue lasting six months or more as a main symptom were recruited, and the Centers for Disease Control (CDC) case definition was applied to classify CFS.

RESULTS: Approximately two-thirds (69%) of patients had chronic fatigue and not CFS. The duration of fatigue (32 months) and perceived control over fatigue were similar between groups; however, fatigue, functioning, associated symptoms, and psychological distress were more severe in the patients in the CFS group, who also consulted their GP significantly more frequently, were twice as likely to be depressed, and more than twice as likely to be unemployed. About half (CFS = 50%; chronic fatigue = 55%) in each group attributed their fatigue to mainly psychological causes.

CONCLUSIONS: In primary care, CFS is a more severe illness than chronic fatigue, but non-CFS chronic fatigue is associated with significant fatigue and is reported at least twice as often. That half of patients, irrespective of CFS status, attribute their fatigue to psychological causes, more than is observed in secondary care, indicates an openness to the psychological therapies provided in that setting. More evidence on the natural history of chronic fatigue and CFS in primary care is required, as are trials of complex interventions. The results may help determine the usefulness of differentiating between chronic fatigue and CFS.

 

Source: Darbishire L, Ridsdale L, Seed PT. Distinguishing patients with chronic fatigue from those with chronic fatigue syndrome: a diagnostic study in UK primary care. Br J Gen Pract. 2003 Jun;53(491):441-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314617/ (Full article)

 

Differences between patients with chronic fatigue syndrome and with chronic fatigue at an infectious disease clinic in Stockholm, Sweden

Abstract:

Background data were collected from patients presenting with fatigue at the clinic of infectious diseases at Huddinge University Hospital, Stockholm. The main purpose was to look for differences as to demographic and functional status for patients fulfilling criteria for chronic fatigue syndrome (CFS) and chronic fatigue (CF).

A cross-sectional questionnaire survey was performed using a variety of instruments. A thorough medical investigation was performed. No difference was found as to social situation, occupation and illness attributions for patients in the two categories. Patients with CFS reported in general a higher degree of ‘sickness’ with more self-reported somatic symptoms, more self-reported functional impairment and more absence from work. A higher degree of psychiatric comorbidity was observed in CF than in CFS patients. A majority of CFS patients (80%) had an acute infectious onset compared to 43% in the CF group.

Presently used criteria might, according to findings presented here, define two different patient categories in a population characterized by severe, prolonged fatigue. Because CFS patients (compared to patients with CF) have more somatic symptoms, more often report an infectious, sudden onset and have less psychiatric comorbidity, and CF patients seem to have more of an emotional, burn-out-like component one could speculate about the existence of different pathogenetic backgrounds behind the two diagnoses.

 

Source: Evengård B, Jonzon E, Sandberg A, Theorell T, Lindh G. Differences between patients with chronic fatigue syndrome and with chronic fatigue at an infectious disease clinic in Stockholm, Sweden. Psychiatry Clin Neurosci. 2003 Aug;57(4):361-8. http://onlinelibrary.wiley.com/doi/10.1046/j.1440-1819.2003.01132.x/full (Full article)