Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome

Abstract:

OBJECTIVE: It has been suggested that a hypofunctional hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated release of pro-inflammatory cytokines during stress. As pro-inflammatory cytokines are involved in the induction of sickness behavior and thus constitute a potential physiological correlate of stress-induced symptom exacerbation in chronic fatigue syndrome, we set out to evaluate the LPS-induced production of pro-inflammatory cytokines during psychosocial stress in CFS and healthy controls.

METHOD: Twenty-one CFS patients and 20 healthy controls matched for age and gender underwent a standardized psychosocial stress test (Trier social stress test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma cortisol levels were measured before and repeatedly following exposure to the stressor. Lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after the stress test.

RESULTS: CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF-alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels.

CONCLUSION: CFS patients do not show an exaggerated secretion of LPS-induced cytokines. Although cortisol responses to stress were normal, pro-inflammatory cytokine levels in CFS patients were significantly attenuated. Possible intracellular mechanisms, such as for example an enhanced sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity to catecholaminergic stimulation, and a disruption of intracellular activation are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are generally related to fatigue scores. However, in CFS patients this association is of greater magnitude and can also be observed for TNF-alpha.

 

Source: Gaab J, Rohleder N, Heitz V, Engert V, Schad T, Schürmeyer TH, Ehlert U. Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome. Psychoneuroendocrinology. 2005 Feb;30(2):188-98. http://www.ncbi.nlm.nih.gov/pubmed/15471616

 

Manual-based cognitive behaviour therapy for chronic fatigue syndrome: therapists’ adherence and perceptions

Abstract:

Several randomized controlled trials have indicated that cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome. In 1 of these studies 13 therapists applied cognitive behaviour therapy for chronic fatigue syndrome in 83 chronic fatigue syndrome patients.

In the present study therapists’ adherence and perceptions of the manual are studied. Following completion of the study the therapists were asked to complete a questionnaire. Audiotaped sessions were conducted to verify the therapists’ adherence. Analyses of the audiotapes showed that in 87% of the sessions this appeared to be the case.

The questionnaire revealed that the therapists found it more difficult to treat patients with chronic fatigue syndrome than to treat patients with psychological or other physical problems. Treatment aspects posing the most problems were integrating individual problems into the standardized treatment, dealing with the patients’ lack of confidence in the treatment and handling insufficient motivation.

 

Source: Bazelmans E, Prins JB, Hoogveld S, Bleijenberg G. Manual-based cognitive behaviour therapy for chronic fatigue syndrome: therapists’ adherence and perceptions. Cogn Behav Ther. 2004;33(3):143-50. http://www.ncbi.nlm.nih.gov/pubmed/15471384

 

Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study

Abstract:

OBJECTIVE: To study childhood risk factors for chronic fatigue syndrome in adult life.

DESIGN: Examination of data from the 1970 British birth cohort.

PARTICIPANTS: 16,567 babies born 5-11 April 1970, followed up at 5, 10, 16, and 29-30 years.

MAIN OUTCOME MEASURES: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) identified by self report at age 30 years. Data from childhood from questionnaires given to parents and teachers. Maternal mental health assessed with the malaise inventory.

RESULTS: 93 (0.8%, 95% confidence interval 0.7 to 1.0) of 11 261 participants reported ever having CFS/ME, and 48 (0.4%, 0.3 to 0.6) had the condition currently. Higher risk of CFS/ME was associated with having a limiting longstanding condition in childhood (odds ratio 2.3, 1.4 to 3.9), female sex (2.3, 1.4 to 2.6), and high social class in childhood (2.2, 1.4 to 3.5). Higher levels of exercise in childhood were associated with lower risk (0.5, 0.2 to 0.9). Maternal psychological disorder, psychological problems in childhood, birth weight, birth order, atopy, obesity, school absence, academic ability, and parental illness were not associated with risk of CFS/ME.

CONCLUSIONS: We identified no association between maternal or child psychological distress, academic ability, parental illness, atopy, or birth order and increasing risk of lifetime CFS/ME. Sedentary behaviour increased the risk.

Comment in: What causes chronic fatigue syndrome? [BMJ. 2004]

 

Source: Viner R, Hotopf M. Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. BMJ. 2004 Oct 23;329(7472):941. Epub 2004 Oct 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524102/ (Full article)

 

 

Kinesiophobia in chronic fatigue syndrome: assessment and associations with disability

Abstract:

OBJECTIVES: To investigate aspects of the validity of the total scores of the Tampa Scale for Kinesiophobia (TSK), Dutch Version, which was modified to make it an appropriate questionnaire for the assessment of kinesiophobia (fear of movement) in chronic fatigue syndrome (CFS) patients (the Dutch TSK-CFS), and, using this assessment tool, to examine the associations between kinesiophobia, exercise capacity, and activity limitations and participation restrictions in patients with CFS.

DESIGN: Prospective observational studies.

SETTING: An outpatient fatigue clinic.

PARTICIPANTS: In the first study, 40 patients fulfilling the 1994 US Centers for Disease Control and Prevention (CDC) criteria for CFS were enrolled. The sample of the second study consisted of 51 CDC-defined patients with CSF.

INTERVENTIONS: Not applicable. Main outcome measures Study 1: Subjects completed a set of questionnaires; the Utrechtse Coping List (UCL), the Dutch TSK-CFS, and the Dutch Baecke Questionnaire of Habitual Physical Activity. Study 2: All patients completed 2 questionnaires (Chronic Fatigue Syndrome Activities and Participation Questionnaire [CFS-APQ], Dutch TSK-CFS) and performed a maximal exercise stress test on a bicycle ergometer. The heart rate was monitored continuously by use of an electrocardiograph. Metabolic and ventilatory parameters were measured through spirometry.

RESULTS: Study 1: The Cronbach alpha coefficient for the individual item scores on the TSK-CFS was .80. The total scores on the Dutch TSK-CFS showed a statistically significant correlation with both the avoidance/abide subscale of the UCL (Spearman rho=.35, P=.029) and the total score of the Baecke Questionnaire (rho=-.45, P=.004). Study 2: The total scores on the Dutch TSK-CFS showed a statistically significant correlation with the total scores on the CFS-APQ (rho=.39, P=.004). No statistically significant associations were observed between the exercise capacity parameters and the total scores on the Dutch TSK-CFS.

CONCLUSIONS: These results provide evidence for the internal consistency and the convergent and congruent validity of the scores obtained by use of the Dutch TSK-CFS. Kinesiophobia appears to be associated with activity limitations/participation restrictions but not with exercise capacity in patients with CFS.

 

Source: Nijs J, De Meirleir K, Duquet W. Kinesiophobia in chronic fatigue syndrome: assessment and associations with disability. Arch Phys Med Rehabil. 2004 Oct;85(10):1586-92. http://www.ncbi.nlm.nih.gov/pubmed/15468015

 

Chronic/post-viral fatigue syndrome

Chronic / post-viral fatigue syndrome is the diagnosis term Rikstrygdeverket opted for the ICD-10 called “benign myalgic encephalomyelitis / post-viral fatigue syndrome.” Benign myalgic encephalomyelitis has since 1956 designated the epidemic form of this disease picture.”Chronic Fatigue Syndrome” is the Norwegian translation of “chronic fatigue syndrome” which has different meanings according to how it is defined.

Methodological differences from evaluation and diagnosis of chronic / post-viral fatigue syndrome from a study of chronic fatigue syndrome, and states have different therapeutic implications. Rikstrygdeverket bases its diagnosis in the original research definition of “chronic fatigue syndrome” from the Centers for Disease Control in 1988, an illness which later was recognized as benign myalgic encephalomyelitis.

You can read the rest of this article here: http://tidsskriftet.no/article/1072526

 

Source: Kreyberg S. Chronic/post-viral fatigue syndrome. Tidsskr Nor Laegeforen. 2004 Sep 23;124(18):2382-3. [Article in Norwegian] http://tidsskriftet.no/article/1072526  (Full article)

 

Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health

Abstract:

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system.

A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.

Data suggest that persons with CFS manifest changes in immune responses that fall outside normative ranges, but current research does not provide definitive evidence on whether these immune abnormalities are a cause or result of the illness. It has become clear that CFS cannot be understood based on single measurements of immune, endocrine, cardiovascular, or autonomic nervous system dysfunction. This panel encourages a new emphasis on multidisciplinary research into CFS.

 

Source: Gerrity TR, Papanicolaou DA, Amsterdam JD, Bingham S, Grossman A, Hedrick T, Herberman RB, Krueger G, Levine S, Mohagheghpour N, Moore RC,Oleske J, Snell CR; CFIDS Association of America. Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health. Neuroimmunomodulation. 2004;11(6):351-7. http://www.ncbi.nlm.nih.gov/pubmed/15467349

 

Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome

Abstract:

OBJECTIVE: We have investigated whether central activation failure (CAF) is increased during local muscle fatigue in chronic fatigue syndrome (CFS).

METHODS: Fourteen female CFS patients and 14 age-matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was applied. Force and 5 channel surface EMG (sEMG) were registered.

RESULTS: Although force responses upon stimulation during rest did not differ between patients and controls, MVC was significantly lower in patients. Already at the beginning of sustained MVC, CFS patients showed significantly larger CAF than controls (36.5+/-17.0% and 12.9+/-13.3%, respectively). For all individual patients mean CAF over the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction.

CONCLUSIONS: Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue.

SIGNIFICANCE: CFS patients show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.

 

Source: Schillings ML, Kalkman JS, van der Werf SP, van Engelen BG, Bleijenberg G, Zwarts MJ. Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome. Clin Neurophysiol. 2004 Nov;115(11):2518-24. http://www.ncbi.nlm.nih.gov/pubmed/15465441

 

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Abstract:

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.

METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects.

RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects.

CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.

 

Source: Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N. Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol. 2004 Oct 4;4(1):14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524491/

 

Subjective and objective sleepiness in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

STUDY OBJECTIVE: To examine the association of chronic fatigue syndrome (CFS) with measures of objective and subjective sleepiness.

DESIGN: Monozygotic co-twin control study.

SETTING: Academic medical center.

PATIENTS AND PARTICIPANTS: Twenty monozygotic twin pairs discordant for CFS.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: All twins completed an Epworth Sleepiness Scale (ESS), 4 Stanford Sleepiness Scales (SSS), and underwent a standard 4-nap multiple sleep latency test. We compared the ESS scores, average SSS scores, and average sleep latency in CFS and healthy twins. The CFS twins reported more sleepiness as measured by mean scores on the ESS (10.9 vs 8.2; 95% confidence interval [CI] = 0.3-5.5; P = .03) and the SSS (3.4 versus 2.1; 95% CI = 0.7-1.9; P < .001). The mean sleep latency on the Multiple Sleep Latency Test was not significantly different between the CFS and healthy twins (8.9 vs 10.0 minutes; 95% CI -4.4-1.7; P = .33). Mean SSS scores increased among the CFS twins and decreased among healthy twins from nap 1 to nap 4 (P < .001). The individual ESS scores and mean sleep latencies on the Multiple Sleep Latency Test were negatively correlated for all the twins (Pearson’s r = – 0.40; P = .01), with a slightly stronger association among the healthy twins (Pearson’s r = -0.42, P = .07) than the CFS twins (Pearson’s r = -0.36, P = .15).

CONCLUSIONS: CFS twins reported significantly more subjective sleepiness than their healthy co-twins despite similar nonpathologic mean sleep latencies on the Multiple Sleep Latency Test. Patients with CFS may mistake their chronic disabling fatigue for sleepiness.

 

Source: Watson NF, Jacobsen C, Goldberg J, Kapur V, Buchwald D. Subjective and objective sleepiness in monozygotic twins discordant for chronic fatigue syndrome. Sleep. 2004 Aug 1;27(5):973-7. http://www.ncbi.nlm.nih.gov/pubmed/15453557

 

Chronic fatigue syndrome impairs circadian rhythm of activity level

Abstract:

Some of the symptoms of chronic fatigue syndrome (CFS) are the same as for disrupted circadian rhythm. Activity level is frequently used to study circadian rhythm. Continuous waist activity measurements taken every minute 24 h/day for from 5 to 7 days in 10 controls and from 2 to 7 days in 8 patients with CFS yielded two primary findings: (a) lower daytime activity and (b) less regular activity-rest cycles in persons with CFS than in controls.

 

Source: Tryon WW, Jason L, Frankenberry E, Torres-Harding S. Chronic fatigue syndrome impairs circadian rhythm of activity level. Physiol Behav. 2004 Oct 15;82(5):849-53. http://www.ncbi.nlm.nih.gov/pubmed/15451649