Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome

Abstract:

BACKGROUND: Studies of hypothalamic-pituitary-adrenal (HPA) axis function in chronic fatigue syndrome (CFS) point to hypofunction, although there are negative reports. Suggested mechanisms include a reduced hypothalamic or supra-hypothalamic stimulus to the HPA axis and enhanced sensitivity to the negative feedback of glucocorticoids. The aim of the current study was to investigate HPA axis function in CFS with the dexamethasone/corticotropin-releasing factor (Dex/CRF) test, in analogy with research in affective disorders.

METHOD: Thirty-four well-characterized female CFS patients and 25 healthy control subjects participated in the low-dose Dex/CRF test. Current major depressive episode was an exclusion criterion. History of early-life stress (ELS) was assessed with the Structured Trauma Interview.

RESULTS: Salivary cortisol responses after 0.5 mg Dex were lower in CFS patients than in controls (before 100 microg CRF, p=0.038; after 100 microg CRF, p=0.015). A secondary analysis revealed an influence of early-life stress and of oestrogen intake. After removal of the 10 participants who were taking an oral oestrogen, patients without a history of ELS showed lower cortisol responses than patients with ELS and controls (before CRF, p=0.005; after CRF, p=0.008).

CONCLUSIONS: CFS is globally associated with reduced cortisol responses in the combined low-dose Dex/CRF test, but this effect is only clearly present in CFS patients without a history of ELS. This study provides further support for an enhanced glucocorticoid negative feedback and/or a reduced central HPA axis drive in CFS. Furthermore, it demonstrates that ELS is an important variable to consider in CFS research.

 

Source: Van Den Eede F, Moorkens G, Hulstijn W, Van Houdenhove B, Cosyns P, Sabbe BG, Claes SJ. Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome. Psychol Med. 2008 Jul;38(7):963-73. Epub 2007 Sep 6. https://www.ncbi.nlm.nih.gov/pubmed/17803834

 

The chronic fatigue syndrome: a comparative pathway analysis

Abstract:

In this paper, we introduce a method to detect pathological pathways of a disease. We aim to identify biological processes rather than single genes affected by the chronic fatigue syndrome (CFS). So far, CFS has neither diagnostic clinical signals nor abnormalities that could be diagnosed by laboratory examinations. It is also unclear if the CFS represents one disease or can be subdivided in different categories. We use information from clinical trials, the gene ontology (GO) database as well as gene expression data to identify undirected dependency graphs (UDGs) representing biological processes according to the GO database. The structural comparison of UDGs of sick versus non-sick patients allows us to make predictions about the modification of pathways due to pathogenesis.

 

Source: Emmert-Streib F. The chronic fatigue syndrome: a comparative pathway analysis. J Comput Biol. 2007 Sep;14(7):961-72. https://www.ncbi.nlm.nih.gov/pubmed/17803373

 

Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance

Data from other countries indicate that chronic fatigue syndrome (also known as myalgic encephalomyelitis or myalgic encephalopathy) (CFS/ME) is relatively common (affecting at least 0.2-0.4% of the population), although good epidemiological data for the United Kingdom are lacking. Many different potential aetiologies for CFS/ME have been investigated, including neurological, endocrine, immunological, genetic, psychiatric, and infectious, but the aetiology cannot yet be fully explained. CFS/ME can cause prolonged illness and disability and substantially affect patients and their families. Although most patients have mild or moderate symptoms, some have severe CFS/ME and are housebound or even unable to move from their bed. Uncertainties about diagnosis and management may exacerbate the impact of symptoms, and patients often encounter delays in diagnosis and difficulty accessing information, support, and potentially helpful therapies.1 This article summarises the most recent guidance from the National Institute for Health and Clinical Excellence (NICE) on diagnosing and managing this condition.2

 

Source: Baker R, Shaw EJ. Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ. 2007 Sep 1;335(7617):446-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962830/ (Full article)

 

Chronic fatigue syndrome or myalgic encephalomyelitis

Comment on: Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. [BMJ. 2007]

The uncertainty inherent in making a diagnosis of chronic fatigue syndrome (CFS) is reflected by the variety of names (such as myalgic encephalomyelitis; ME) it has been given. The names reflect the hope that such labels can impose some certainty where little exists. Many doctors are reluctant to make a diagnosis of CFS, with half not even believing it exists.1 The consequences of this uncertainty and reluctance have been that patients hear mixed messages and often receive poor, if any, care.2 It is therefore a welcome relief that the National Institute for Health and Clinical Excellence (NICE) has just published clinical guidelines on the diagnosis and management of this disease.3 In this week’s BMJ, Baker and Shaw summarise the guidelines.4

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962896/

 

Source: White P, Murphy M, Moss J, Armstrong G, Spencer P. Chronic fatigue syndrome or myalgic encephalomyelitis. BMJ. 2007 Sep 1;335(7617):411-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962896/ (Full article)

 

Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome

Abstract:

OBJECTIVE: We reviewed previous studies that have described an association between abnormal functioning of the hypothalamic-pituitary-adrenal axis and depression. In addition to melancholic depression, a spectrum of conditions may be associated with increased and prolonged activation of the hypothalamic-pituitary-adrenal axis. In contrast another group of states is characterized by hypoactivation of the stress system, rather than sustained activation, in which chronically reduced secretion of corticotropin releasing factor may result in pathological hypoarousal and an enhanced hypothalamic-pituitary-adrenal negative feedback. Patients with atypical depression, seasonal affective disorder and chronic fatigue syndrome fall in this category.

METHOD: The literature data on the overlap between the key-words were reviewed, summarized and discussed.

RESULTS: Many studies suggest that these conditions themselves overlap biologically, showing hypofunction of central corticotropin releasing factor neuronal systems.

CONCLUSIONS: Therefore, in the real world of clinical practice, patients often present in a grey area between classical idiopathic fatigue and early chronic atypical depression and/or seasonal depression. This underscores the potential common biological links underpinning common symptom clusters not only between depression (atypical and seasonal) and chronic fatigue syndrome, but also other conditions characterized by the hypothalamic-pituitary-adrenal axis mainly diminished the corticotropin releasing factor activity.

 

Source: Juruena MF, Cleare AJ. Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome. Rev Bras Psiquiatr. 2007 May;29 Suppl 1:S19-26. [Article in Portuguese] http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462007000500005&lng=en&nrm=iso&tlng=en (Full article)

 

Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) have a broad and variable spectrum of signs and symptoms with variable onsets. This report outlines the results of a single-blind, cross-sectional research project that extensively investigated a large cohort of 100 CFS patients and 82 non fatigued control subjects with the aim of performing a case-control evaluation of alterations in standard blood parameters and urinary amino and organic acid excretion profiles.

Blood biochemistry and full blood counts were unremarkable and fell within normal laboratory ranges. However, the case-control comparison of the blood cell data revealed that CFS patients had a significant decrease in red cell distribution width and increases in mean platelet volume, neutrophil counts, and the neutrophil-lymphocyte ratio.

Evaluation of the urine excretion parameters also revealed a number of anomalies. The overnight urine output and rate of amino acid excretion were both reduced in the CFS group (P < 0.01). Significant decreases in the urinary excretion of asparagine (P < 0.0001), phenylalanine (P < 0.003), the branch chain amino acids (P < 0.005), and succinic acid (P < 0.0001), as well as increases in 3-methylhistidine (P < 0.05) and tyrosine (P < 0.05) were observed.

It was concluded that the urinary excretion and blood parameters data supported the hypothesis that alterations in physiologic homeostasis exist in CFS patients.

 

Source: Niblett SH, King KE, Dunstan RH, Clifton-Bligh P, Hoskin LA, Roberts TK, Fulcher GR, McGregor NR, Dunsmore JC, Butt HL, Klineberg I, Rothkirch TB. Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome. Exp Biol Med (Maywood). 2007 Sep;232(8):1041-9. https://www.ncbi.nlm.nih.gov/pubmed/17720950

 

Hyperventilation in patients with chronic fatigue syndrome: the role of coping strategies

Abstract:

Hyperventilation has been suggested as a concomitant and possible maintaining factor that may contribute to the symptom pattern of chronic fatigue syndrome (CFS). Because patients accepting the illness and trying to live with it seem to have a better prognosis than patients chronically fighting it, we investigated breathing behavior during different coping response sets towards the illness in patients with CFS (N=30, CDC criteria).

Patients imagined a relaxation script (baseline), a script describing a coping response of hostile resistance, and a script depicting acceptance of the illness and its (future) consequences. During each imagery trial, end-tidal PCO2 (Handheld Capnograph, Oridion) was measured. After each trial, patients filled out a symptom checklist. Results showed low resting values of PetCO2 overall, while only imagery of hostile resistance triggered a decrease and deficient recovery of PetCO2. Also, more hyperventilation complaints and complaints of other origin were reported during hostile resistance imagery compared with acceptance and relaxation.

In conclusion, hostile resistance seems to trigger both physiological and symptom perception processes contributing to the clinical picture of CFS.

 

Source: Bogaerts K, Hubin M, Van Diest I, De Peuter S, Van Houdenhove B, Van Wambeke P, Crombez G, Van den Bergh O. Hyperventilation in patients with chronic fatigue syndrome: the role of coping strategies. Behav Res Ther. 2007 Nov;45(11):2679-90. Epub 2007 Jul 20. https://www.ncbi.nlm.nih.gov/pubmed/17719001

 

Chronic fatigue syndrome treated by acupuncture and moxibustion in combination with psychological approaches in 310 cases

Abstract:

OBJECTIVE: To observe clinical therapeutic effect of acupuncture and moxibustion combined with a psychological approach on chronic fatigue syndrome (CFS).

METHODS: The treatment was given by acupuncture plus moxibustion combined with a psychological approach based on differentiation of symptoms and signs in 310 cases.

RESULTS: Of 310 cases observed, 275 cases (88.7%) were clinically cured, 28 cases (9%) improved, and 7 cases (2.3%) failed.

CONCLUSION: Acupuncture plus moxibustion combined with a psychological approach is an effective therapy for CFS.

 

Source: Guo J.Chronic fatigue syndrome treated by acupuncture and moxibustion in combination with psychological approaches in 310 cases. J Tradit Chin Med. 2007 Jun;27(2):92-5. http://www.journaltcm.com/modules/Journal/contents/stories/072/3.pdf (Full article)

 

Identity and coping experiences in Chronic Fatigue Syndrome: a synthesis of qualitative studies

Abstract:

OBJECTIVE: To provide insight into patients’ and doctors’ experiences with CFS.

METHODS: We compiled available qualitative studies and applied meta-ethnography to identify and translate across the studies. Analysis provided second-order interpretation of the original findings and developed third-order constructs from a line of arguments.

RESULTS: Twenty qualitative studies on CFS experiences were identified. Symptom experiences and the responses from significant others could jeopardise the patients’ senses of identity. They felt severely ill, yet blamed and dismissed. Patients’ beliefs and causal attributions oppose the doctor’s understanding of the condition. For the patient, getting a diagnosis and knowing more was necessary for recovery. Doctors were reluctant towards the diagnosis, and struggle to maintain professional authority. For patients, experience of discreditation could lead to withdrawal and behavioural disengagement.

CONCLUSION: The identities of CFS patients are challenged when the legitimacy of their illness is questioned. This significant burden adds to a loss of previously established identity and makes the patient more vulnerable than just suffering from the symptoms. CFS patients work hard to cope with their condition by knowing more, keeping a distance to protect themselves and learning more about their limits.

PRACTICE IMPLICATIONS: Doctors can support patients’ coping by supporting the strong sides of the patients instead of casting doubt upon them.

 

Source: Larun L, Malterud K. Identity and coping experiences in Chronic Fatigue Syndrome: a synthesis of qualitative studies. Patient Educ Couns. 2007 Dec;69(1-3):20-8. Epub 2007 Aug 14. https://www.ncbi.nlm.nih.gov/pubmed/17698311

 

Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta

Abstract:

There is now some evidence that chronic fatigue syndrome is accompanied by an activation of the inflammatory response system and by increased oxidative and nitrosative stress. Nuclear factor kappa beta (NFkappabeta) is the major upstream, intracellular mechanism which regulates inflammatory and oxidative stress mediators. In order to examine the role of NFkappabeta in the pathophysiology of CFS, this study examines the production of NFkappabeta p50 in unstimulated, 10 ng/mL TNF-alpha (tumor necrosis factor alpha) and 50 ng/mL PMA (phorbolmyristate acetate) stimulated peripheral blood lymphocytes of 18 unmedicated patients with CFS and 18 age-sex matched controls.

The unstimulated (F=19.4, df=1/34, p=0.0002), TNF-alpha-(F=14.0, df=1/34, p=0.0009) and PMA-(F=7.9, df=1/34, p=0.008) stimulated production of NFkappabeta were significantly higher in CFS patients than in controls. There were significant and positive correlations between the production of NFkappabeta and the severity of illness as measured with the FibroFatigue scale and with symptoms, such as aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection.

The results show that an intracellular inflammatory response in the white blood cells plays an important role in the pathophysiology of CFS and that previous findings on increased oxidative stress and inflammation in CFS may be attributed to an increased production of NFkappabeta. The results suggest that the symptoms of CFS, such as fatigue, muscular tension, depressive symptoms and the feeling of infection reflect a genuine inflammatory response in those patients. It is suggested that CFS patients should be treated with antioxidants, which inhibit the production of NFkappabeta, such as curcumin, N-Acetyl-Cysteine, quercitin, silimarin, lipoic acid and omega-3 fatty acids.

 

Source: Maes M, Mihaylova I, Bosmans E. Not in the mind of neurasthenic lazybones but in the cell nucleus: patients with chronic fatigue syndrome have increased production of nuclear factor kappa beta. Neuro Endocrinol Lett. 2007 Aug;28(4):456-62. https://www.ncbi.nlm.nih.gov/pubmed/17693979