CFS: A Review of Epidemiology and Natural History Studies

Abstract:

Almost all studies with samples of patients who have chronic fatigue syndrome (CFS) have relied on referrals from physicians or health facilities. Under-served minorities, who not only tend to manifest higher levels of chronic illness, but are also less likely to seek and receive adequate medical care, have not been represented in these studies (1). This may have contributed to an under-estimation of CFS among minority groups (2). Few studies have derived their samples from socioeconomically and ethnically diverse community-based populations. A technical report issued by the Agency for Healthcare Research and Quality (3) concluded that estimating rates of recovery/improvement or relapse from CFS are not possible because there are so few natural history studies and those that are available have involved selected referral populations.

This paper provides a review of epidemiologic studies of CFS followed by a discussion of diagnostic issues and risk factors for the illness. Findings from Jason et al.’s (4) epidemiologic study in a multi-ethnic, economically diverse urban area are highlighted as this research group is now examining the natural course of CFS over the past 10 years with this community-based sample. The current study will add to current epidemiologic and risk factors research by assessing the course, progression, and risk factors of CFS among a demographically diverse sample of participants who are unbiased by illness, help-seeking behaviors, or differential access to the health care system.

 

Source: Jason LA, Porter N, Brown M, Anderson V, Brown A, Hunnell J, Lerch A. CFS: A Review of Epidemiology and Natural History Studies. Bull IACFS ME. 2009;17(3):88-106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021257/ (Full article)

 

A controlled study of the effect of a mindfulness-based stress reduction technique in women with multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia

Abstract:

BACKGROUND: The objective of this study was to examine the effect of a mindfulness-based stress reduction (MBSR) program on women diagnosed with conditions such as multiple chemical sensitivity (MCS), chronic fatigue syndrome (CFS), and fibromyalgia (FM).

METHODS: The intervention group underwent a 10-week MBSR program. Symptoms Checklist Inventory (SCL-90R) was used as outcome measure and was administered before the start of the program (pre-), immediately upon completion (post-) and at three-month follow-up. Women on the wait list to receive treatment at the Nova Scotia Environmental Health Centre were used as control subjects for the study.

RESULTS: A total of 50 participants in the intervention group and 26 in the wait-list controls group were recruited for this study. Global scores in the intervention group reached statistical significance pre-post (<0.0001) and at pre-follow-up (<0.0001) while the global scores in the control group remained the same. Five of nine and eight of nine subscales of the SCL-90R showed improvement of statistical significance in MBSR group following treatment and at three-month follow-up.

CONCLUSIONS: The study showed the importance of complementary interventions such as MBSR techniques in the reduction of psychological distress in women with chronic conditions.

 

Source: Sampalli T, Berlasso E, Fox R, Petter M. A controlled study of the effect of a mindfulness-based stress reduction technique in women with multiple chemical sensitivity, chronic fatigue syndrome, and fibromyalgia. J Multidiscip Healthc. 2009 Apr 7;2:53-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004557/(Full article)

 

A Bayesian approach to gene-gene and gene-environment interactions in chronic fatigue syndrome

Abstract:

INTRODUCTION: In the study of genomics, it is essential to address gene-gene and gene-environment interactions for describing the complex traits that involves disease-related mechanisms. In this work, our goal is to detect gene-gene and gene-environment interactions resulting from the analysis of chronic fatigue syndrome patients’ genetic and demographic factors including SNPs, age, gender and BMI.

MATERIALS & METHODS: We employed the dataset that was original to the previous study by the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Research Group. To investigate gene-gene and gene-environment interactions, we implemented a Bayesian based method for identifying significant interactions between factors. Here, we employed a two-stage Bayesian variable selection methodology based on Markov Chain Monte Carlo approaches.

RESULTS: By applying our Bayesian based approach, NR3C1 was found in the significant two-locus gene-gene effect model, as well as in the significant two-factor gene-environment effect model. Furthermore, a significant gene-environment interaction was identified between NR3C1 and gender. These results support the hypothesis that NR3C1 and gender may play a role in biological mechanisms associated with chronic fatigue syndrome.

CONCLUSION: We demonstrated that our Bayesian based approach is a promising method to assess the gene-gene and gene-environment interactions in chronic fatigue syndrome patients by using genetic factors, such as SNPs, and demographic factors such as age, gender and BMI.

 

Source: Lin E, Hsu SY. A Bayesian approach to gene-gene and gene-environment interactions in chronic fatigue syndrome. Pharmacogenomics. 2009 Jan;10(1):35-42. Doi: 10.2217/14622416.10.1.35. https://www.ncbi.nlm.nih.gov/pubmed/19102713

 

Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings?

Abstract:

OBJECTIVE: The validity of the diagnosis of chronic fatigue syndrome and related chronic fatigue states remains controversial, particularly in psychiatry. This project utilized international epidemiological and clinical research data to test construct validity across diagnostic categories, health-care settings and countries. Relevant demographic, symptom and diagnostic data were obtained from 33 studies in 21 countries. The subjects had fatigue lasting 1-6 months (prolonged fatigue), or >6 months (chronic fatigue), or met diagnostic criteria for chronic fatigue syndrome.

METHOD: Common symptom domains were derived by factor analytic techniques. Mean scores on each symptom factor were compared across diagnostic categories, health-care settings and countries.

RESULTS: Data were obtained on 37,724 subjects (n = 20,845 female, 57%), including from population-based studies (n = 15,749, 42%), studies in primary care (n = 19 472, 52%), and secondary or specialist tertiary referral clinics (n = 2503, 7%). The sample included 2013 subjects with chronic fatigue, and 1958 with chronic fatigue syndrome. A five-factor model of the key symptom domains was preferred (‘musculoskeletal pain/fatigue’, ‘neurocognitive difficulties’, ‘inflammation’, ‘sleep disturbance/fatigue’ and ‘mood disturbance’) and was comparable across subject groups and settings. Although the core symptom profiles were similar, some differences in symptoms were observed across diagnostic categories, health-care settings and between countries.

CONCLUSIONS: The construct validity of chronic fatigue and chronic fatigue syndrome is supported by an empirically derived factor structure from existing international datasets.

 

 

Source: Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D, Lloyd A; International Chronic Fatigue Syndrome Study Group. Collaborators (28) Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Aust N Z J Psychiatry. 2009 Jan;43(1):25-35. Doi: 10.1080/00048670802534432. https://www.ncbi.nlm.nih.gov/pubmed/19085525

 

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study

Abstract:

Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ.

Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate.

CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

 

Source: Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC. Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed. 2009 Apr;22(3):251-8. doi: 10.1002/nbm.1315. https://www.ncbi.nlm.nih.gov/pubmed/18942064

 

Immunological aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterises unexplained disabling fatigue and a combination of non-specific accompanying symptoms for at least 6 months, in the absence of a medical diagnosis that would otherwise explain the clinical presentation. Other common symptoms include headaches, myalgia, arthralgia, and post-exertional malaise; cognitive difficulties, with impaired memory and concentration; unrefreshing sleep; and mood changes.

Similar disorders have been described for at least two centuries and have been differently named neurasthenia, post-viral fatigue, myalgic encephalomyelitis and chronic mononucleosis. Recent longitudinal studies suggest that some people affected by chronic fatigue syndrome improve with time but that most remain functionally impaired for several years. The estimated worldwide prevalence of CFS is 0.4-1% and it affects over 800,000 people in the United States and approximately 240,000 patients in the UK.

No physical examination signs are specific to CFS and no diagnostic tests identify this syndrome. The pathophysiological mechanism of CFS is unclear. The main hypotheses include altered central nervous system functioning resulting from an abnormal immune response against a common antigen; a neuroendocrine disturbance; cognitive impairment caused by response to infection or other stimuli in sentient people. The current concept is that CFS pathogenesis is a multifactorial condition.

Various studies have sought evidence for a disturbance in immunity in people with CFS. An alteration in cytokine profile, a decreased function of natural killer (NK) cells, a presence of autoantibodies and a reduced responses of T cells to mitogens and other specific antigens have been reported. The observed high level of pro-inflammatory cytokines may explain some of the manifestations such as fatigue and flu-like symptoms and influence NK activity. Abnormal activation of the T lymphocyte subsets and a decrease in antibody-dependent cell-mediated cytotoxicity have been described. An increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR activation markers have been reported, and a decrease in CD11b expression associated with an increased expression of CD28+ T subsets has been observed. This review discusses the immunological aspects of CFS and offers an immunological hypothesis for the disease processes.

 

Source: Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev. 2009 Feb;8(4):287-91. doi: 10.1016/j.autrev.2008.08.003. Epub 2008 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/18801465

 

Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection

Abstract:

The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFN gamma) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS).

CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFN gamma increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups.

Our results suggest that TJ-41 combined with IFN gamma might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.

 

Source: Chen R, Moriya J, Luo X, Yamakawa J, Takahashi T, Sasaki K, Yoshizaki F. Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection. Immunopharmacol Immunotoxicol. 2009 Jun;31(2):238-45. doi: 10.1080/08923970802391525.https://www.ncbi.nlm.nih.gov/pubmed/18791913