The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome

Abstract:

The hypothalamo-pituitary-adrenal (HPA) axis plays a major role in the regulation of responses to stress. Human stress-related disorders such as chronic fatigue syndrome (CFS), fibromyalgia syndrome (FMS), chronic pelvic pain and post-traumatic stress disorder are characterized by alterations in HPA axis activity. However, the role of the HPA axis alterations in these stress-related disorders is not clear.

Most studies have shown that the HPA axis is underactive in the stress-related disorders, but contradictory results have also been reported, which may be due to the patients selected for the study, the methods used for the investigation of the HPA axis, the stage of the syndrome when the tests have been done and the interpretation of the results.

There is no structural abnormality in the endocrine organs which comprise the HPA axis, thus it seems that hypocortisolemia found in the patients with stress-related disorder is functional. It may be also an adaptive response of the body to chronic stress. In this review, tests used in the assessment of HPA axis function and the HPA axis alterations found in CFS and FMS are discussed in detail.

 

Source: Tanriverdi F, Karaca Z, Unluhizarci K, Kelestimur F. The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome. Stress. 2007 Mar;10(1):13-25. https://www.ncbi.nlm.nih.gov/pubmed/17454963

 

Is cognitive behaviour therapy for chronic fatigue syndrome also effective for pain symptoms?

Abstract:

Patients with chronic fatigue syndrome (CFS) frequently report chronic pain symptoms. Cognitive behavioural therapy (CBT) for CFS results in a reduction of fatigue, but is not aimed at pain symptoms. In this study, we tested the hypothesis that a successful treatment of CFS can also lead to a reduction of pain. The second objective was to explore possible mechanisms of changes in pain. The third objective was to assess the predictive value of pain for treatment outcome. Data from two previous CBT studies were used, one of adult CFS patients (n=96) and one of adolescent CFS patients (n=32).

Pain severity was assessed with a daily self-observation list at baseline and post-treatment. The location of pain in adults was assessed with the McGill Pain Questionnaire (MPQ). Patients were divided into recovered and non-recovered groups. Recovery was defined as reaching a post-treatment level of fatigue within normal range. Recovered adult and adolescent CFS patients reported a significant reduction of pain severity compared to non-recovered patients. Recovered adult patients also had fewer pain locations following treatment. The decrease in fatigue predicted the change in pain severity. In adult patients, a higher pain severity at baseline was associated with a negative treatment outcome.

 

Source: Knoop H, Stulemeijer M, Prins JB, van der Meer JW, Bleijenberg G. Is cognitive behaviour therapy for chronic fatigue syndrome also effective for pain symptoms? Behav Res Ther. 2007 Sep;45(9):2034-43. Epub 2007 Mar 14. https://www.ncbi.nlm.nih.gov/pubmed/17451642

 

The prevalence of chronic fatigue syndrome in Nigeria

Abstract:

The present study found adult rates of chronic fatigue syndrome (CFS) in Nigeria that were somewhat higher than rates from community-based CFS epidemiologic studies in the USA. The rates of chronic fatigue for both adults and children were also higher than in existing community-based studies. It is possible that the presence of several fatiguing illnesses such as malaria and typhoid, the lack of adequate healthcare resources and poverty in Nigeria, place individuals at greater risk for fatigue and its syndromes. There is a need for more epidemiologic studies on the prevalence and sociodemographic characteristics of CFS in developing countries.

 

Source: Njoku MG, Jason LA, Torres-Harding SR. The prevalence of chronic fatigue syndrome in Nigeria. J Health Psychol. 2007 May;12(3):461-74. https://www.ncbi.nlm.nih.gov/pubmed/17439996

 

Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome?

Abstract:

BACKGROUND: Cognitive behavioural therapy (CBT) for chronic fatigue syndrome (CFS) leads to a decrease in symptoms and disabilities. There is controversy about the nature of the change following treatment; some suggest that patients improve by learning to adapt to a chronic condition, others think that recovery is possible. The objective of this study was to find out whether recovery from CFS is possible after CBT.

METHODS: The outcome of a cohort of 96 patients treated for CFS with CBT was studied. The definition of recovery was based on the absence of the criteria for CFS set up by the Center for Disease Control (CDC), but also took into account the perception of the patients’ fatigue and their own health. Data from healthy population norms were used in calculating conservative thresholds for recovery.

RESULTS: After treatment, 69% of the patients no longer met the CDC criteria for CFS. The percentage of recovered patients depended on the criteria used for recovery. Using the most comprehensive definition of recovery, 23% of the patients fully recovered. Fewer patients with a co-morbid medical condition recovered.

CONCLUSION: Significant improvement following CBT is probable and a full recovery is possible. Sharing this information with patients can raise the expectations of the treatment, which may enhance outcomes without raising false hopes.

Copyright 2007 S. Karger AG, Basel.

 

Source: Knoop H, Bleijenberg G, Gielissen MF, van der Meer JW, White PD. Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom. 2007;76(3):171-6. https://www.ncbi.nlm.nih.gov/pubmed/17426416

 

Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls

Abstract:

Hemodynamic dysfunction is documented in chronic fatigue syndrome (CFS). This study was conducted to investigate cardiovascular responses to orthostatic stress in adolescents with CFS, using a novel procedure for tilt-table testing.

A total of 27 adolescents with CFS and 33 healthy control subjects with equal age and gender distribution underwent 15 minutes of 20 degrees head-up tilt testing. Heart rate, systolic blood pressure (BP), mean BP, diastolic BP, stroke index, total peripheral resistance index, end-diastolic volume index, and acceleration index were continuously and noninvasively recorded.

At rest, patients with CFS had higher total peripheral resistance index values (p<0.01) and lower stroke index and end-diastolic volume index values (p<0.05) than controls. During 20 degrees head-up tilt testing, patients with CFS had greater increases in heart rate, diastolic BP (p<0.001), mean BP (p<0.01), and total peripheral resistance index (p<0.05) than controls and greater decreases in stroke index (p<0.05). Syncope or near syncope was not observed.

In conclusion, this study found that adolescents with CFS have significant abnormalities of cardiovascular regulation in response to mild orthostatic stress, differentiating them from healthy controls.

 

Source: Wyller VB, Due R, Saul JP, Amlie JP, Thaulow E. Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls. Am J Cardiol. 2007 Apr 1;99(7):997-1001. Epub 2007 Feb 16. https://www.ncbi.nlm.nih.gov/pubmed/17398200

 

Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis /encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioural therapy and graded exercise therapy. The latter two therapies have been found to be efficacious in small trials, but patient organisations surveys have reported adverse effects. Although pacing has been advocated by patient organisations, it lacks empirical support. Specialist medical care is commonly provided but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone.

METHODS: 600 patients, who meet operationalised diagnostic criteria for CFS, will be recruited from secondary care into a randomised trial of four treatments, stratified by current co morbid depressive episode and different CFS/ME criteria. The four treatments are standardised specialist medical care either given alone, or with adaptive pacing therapy or cognitive behaviour therapy or graded exercise therapy. Supplementary therapies will involve fourteen sessions over 23 weeks and a booster session at 36 weeks. Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self-rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility. The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures.

DISCUSSION: The results of the trial will provide information about the benefits and adverse effects of these treatments, their cost-effectiveness and cost-utility, the process of clinical improvement and the predictors of efficacy.

 

Source: White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol. 2007 Mar 8;7:6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147058/

 

Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVE: Individuals with chronic fatigue syndrome (CFS) experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their cotwins without CFS.

DESIGN: Cotwin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS.

PATIENTS AND SETTING: Fifteen monozygotic twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington.

RESULTS: Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their cotwins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain (P = 0.003) and fatigue (P < 0.001) by their cotwins without CFS.

CONCLUSIONS: These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS.

 

Source: Ullrich PM, Afari N, Jacobsen C, Goldberg J, Buchwald D. Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome. Pain Med. 2007 Apr;8(3):216-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957294/ (Full article)

 

The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) often have concentration and memory problems. Neuropsychological test performance is impaired in at least a subgroup of patients with CFS. Cognitive behavioural therapy (CBT) for CFS leads to a reduction in fatigue and disabilities.

AIM: To test the hypothesis that CBT results in a reduction of self-reported cognitive impairment and in an improved neuropsychological test performance.

METHODS: Data of two previous randomised controlled trials were used. One study compared CBT for adult patients with CFS, with two control conditions. The second study compared CBT for adolescent patients with a waiting list condition. Self-reported cognitive impairment was assessed with questionnaires. Information speed was measured with simple and choice reaction time tasks. Adults also completed the symbol digit-modalities task, a measure of complex attentional function.

RESULTS: In both studies, the level of self-reported cognitive impairment decreased significantly more after CBT than in the control conditions. Neuropsychological test performance did not improve.

CONCLUSIONS: CBT leads to a reduction in self-reported cognitive impairment, but not to improved neuropsychological test performance. The findings of this study support the idea that the distorted perception of cognitive processes is more central to CFS than actual cognitive performance.

 

Source: Knoop H, Prins JB, Stulemeijer M, van der Meer JW, Bleijenberg G. The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance. J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):434-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077788/ (Full article)

 

Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) subjects would produce greater force production in their matching limb during a fatiguing contralateral limb-matching task of the elbow flexors, compared with healthy, matched controls.

Eight CFS subjects and 8 healthy, matched control subjects participated in a fatiguing task that consisted of intermittent submaximal contractions (30% maximal voluntary contraction) of the nondominant arm performed over a 45 min duration. Each minute, the subject attempted to match the force of the nondominant arm with their dominant arm (without visual feedback for the dominant arm).

Results showed that average matching force and ratings of perceived effort values were significantly higher in the CFS group during the fatiguing task (P = 0.04, P = 0.02, respectively). This study demonstrated objectively that CFS subjects experienced a greater sense of effort in the elbow flexors while performing a fatiguing task.

 

Source: Wallman KE, Sacco P. Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome. Res Sports Med. 2007 Jan-Mar;15(1):47-59. https://www.ncbi.nlm.nih.gov/pubmed/17365951

 

Infection and vaccination in chronic fatigue syndrome: myth or reality?

Abstract:

Chronic fatigue syndrome (CFS) is characterized by severe disabling fatigue lasting for more than 6 months associated with physical and mental disturbances such as headache, arthralgia, myalgia, memory impairment, sore throat and tender lymph nodes. The exact pathogenesis is still unknown. Several models were proposed to explain its etiology including chronic infection, endocrine dysfunction, autonomic imbalance, depression, decreased immunity states and an aberrant reaction to infection. No convincing evidence was found to support any of the suggested pathogenic mechanisms.

The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 dominant response. When the response fails to be switched-off, a chronic immune activation occurs and clinically expressed as the symptomatology of CFS. Vaccinations are used in order to stimulate the immune system to induce a persistent immunity against the favorable antigens.

Several syndromes that contain chronic fatigue as one of their symptoms, such as “Gulf war syndrome” and macrophagic myofasciitis were related to vaccinations. Can vaccinations induce the aberrant immune response of CFS? Little is known about this issue. There are some reports on CFS occurring after vaccination, but few prospective and retrospective studies failed to find such an association. A working group of the Canadian Laboratory Center for Disease Control (LCDC) that was founded in order to examine the suspected association between CFS and vaccinations concluded that there is no evidence that relates CFS to vaccination.

Further studies are requested to examine this issue since it is very conceivable that if infection can lead to CFS, vaccination may also lead to it in the same immune-mediated pathogenesis.

 

Source: Appel S, Chapman J, Shoenfeld Y. Infection and vaccination in chronic fatigue syndrome: myth or reality? Autoimmunity. 2007 Feb;40(1):48-53. https://www.ncbi.nlm.nih.gov/pubmed/17364497