Activity of hypothalamic-pituitary-adrenal axis by induction of experimental chronic fatigue syndrome

Abstract:

Changes in the activity of hypothalamic-pituitary adrenal (HPA) axis were investigated in experimental model of chronic fatigue syndrome(CFS) induced by intraperitoneal administration of synthetic double-stranded RNA (polyriboinosinic: polyribocytidylic acid, Poly I : C) to rats in the dose of 3 mg/kg body weight. In order to reveal functional changes in different links of the HPA axis, standard probes with intraperitoneal administration of ACTH and hydrocortisone against the background of cold stress application and Poly I : C injections were performed. A single injection of Poly I : C led to disordered HPA axis functions which was manifested by decreased sensitivity of the cells in the adrenal gland in response to ACTH, and suppression of the mechanism of negative feedback resulting in significant fall of corticosterone concentration in standard assays with ACTH and hydrocortisone administration.

 

Source: Fomicheva EE, Filatenkova TA, Rybakina EG. Activity of hypothalamic-pituitary-adrenal axis by induction of experimental chronic fatigue syndrome. Ross Fiziol Zh Im I M Sechenova. 2009 Jan;95(1):11-8. [Article in Russian] https://www.ncbi.nlm.nih.gov/pubmed/19323439

 

Lower ambulatory blood pressure in chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine blood pressure circadian rhythm in subjects with chronic fatigue syndrome (CFS) and appropriate normal and fatigued controls to correlate parameters of blood pressure regulation with perception of fatigue in an observational cohort study. The cause of CFS remains unknown and there are no effective treatments.

METHODS: To address whether inactivity was a confounder, we performed a 24-hour ambulatory blood pressure monitoring in the following three subject groups: 1) CFS patients (Fukuda Diagnostic criteria) (n = 38); 2) normal controls (n = 120); and 3) a fatigue comparison group (n = 47) with the autoimmune liver disease primary biliary cirrhosis (PBC). All patients completed a measure of fatigue severity (Fatigue Impact Scale). In view of the different demographics between the patient groups, patients were age- and sex-matched on a case-by-case basis to normal controls and blood pressure parameters were compared.

RESULTS: Compared with the control population, the CFS group had significantly lower systolic blood pressure (p < .0001) and mean arterial blood pressure (p = .0002) and exaggerated diurnal variation (p = .009). There was a significant inverse relationship between increasing fatigue and diurnal variation of blood pressure in both the CFS and PBC groups (p < .05).

CONCLUSION: Lower blood pressure and abnormal diurnal blood pressure regulation occur in patients with CFS. We would suggest the need for a randomized, placebo-controlled trial of agents to increase blood pressure such as midodrine in CFS patients with an autonomic phenotype.

 

Source: Newton JL, Sheth A, Shin J, Pairman J, Wilton K, Burt JA, Jones DE. Lower ambulatory blood pressure in chronic fatigue syndrome. Psychosom Med. 2009 Apr;71(3):361-5. doi: 10.1097/PSY.0b013e31819ccd2a. Epub 2009 Mar 17. https://www.ncbi.nlm.nih.gov/pubmed/19297309

 

On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics

Abstract:

Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic.

The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors.

An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia.

Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms.

As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

Comment in: Hypotheses concerning rickettsial microorganisms, autoimmune diseases and new treatment strategies. [Med Hypotheses. 2010]

 

Source: Frykholm BO. On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics. Med Hypotheses. 2009 Jun;72(6):736-9. doi: 10.1016/j.mehy.2008.11.045. Epub 2009 Mar 6. https://www.ncbi.nlm.nih.gov/pubmed/19269110

 

Visible and near-infrared spectral changes in the thumb of patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients show a persistent fatigue condition with muscle pain and impairment of concentration, memory, and sleep. Presently, the physiological basis of CFS remains unclear. In this study, spectroscopic differences in the thumb were compared between 103 CFS patients and 122 healthy controls to examine possible changes of levels of oxygenated or deoxygenated hemoglobin.

METHODS: Visible and near-infrared (Vis-NIR) spectroscopy was used to examine possible changes in the region of 600-1100 nm.

RESULTS: Vis-NIR spectra showed sharp peaks at 694, 970 and 1060 nm and broad peaks in the regions of 740-760 and 830-850 nm. As these peaks are possibly related to oxyhemoglobin, cytochrome c oxidase and water, levels of these factors were compared between the two groups. Statistical analysis of the absorbance of Vis-NIR spectra showed a significant decrease in water content, a significant increase in oxyhemoglobin content, and a significant increase in the oxidation of heme a+a(3) and copper in cytochrome c oxidase in CFS patients.

CONCLUSIONS: These changes imply accelerated blood flow and energy metabolism in the thumbs of CFS patients.

 

Source: Sakudo A, Kato YH, Tajima S, Kuratsune H, Ikuta K. Visible and near-infrared spectral changes in the thumb of patients with chronic fatigue syndrome. Clin Chim Acta. 2009 May;403(1-2):163-6. doi: 10.1016/j.cca.2009.02.010. Epub 2009 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/19248775

 

Illness intrusiveness in myalgic encephalomyelitis: an exploratory study

Abstract:

This study assessed the relationship between illness intrusiveness, symptoms, disability and depression in patients with myalgic encephalomyelitis (ME). Participants were 16 patients with ME and eight patients with ME plus co-morbid disorders. The patients with co-morbid disorders reported greater illness intrusiveness than the patients with ME alone, but there were no differences between the groups on the other variables. Significant correlations were found between illness intrusiveness on the one hand, and fatigue, cognitive dysfunction, disability and depression, on the other. We conclude that ME is a disabling illness, which has a major impact on various life domains.

 

Source: Goudsmit EM, Stouten B, Howes S. Illness intrusiveness in myalgic encephalomyelitis: an exploratory study. J Health Psychol. 2009 Mar;14(2):215-21. Doi: 10.1177/1359105308100205. https://www.ncbi.nlm.nih.gov/pubmed/19237488

 

Does hypothalamic-pituitary-adrenal axis hypofunction in chronic fatigue syndrome reflect a ‘crash’ in the stress system?

Abstract:

The etiopathogenesis of chronic fatigue syndrome (CFS) remains poorly understood. Although neuroendocrine disturbances – and hypothalamic-pituitary-adrenal (HPA) axis hypofunction in particular – have been found in a large proportion of CFS patients, it is not clear whether these disturbances are cause or consequence of the illness.

After a review of the available evidence we hypothesize that that HPA axis hypofunction in CFS, conceptualized within a system-biological perspective, primarily reflects a fundamental and persistent dysregulation of the neurobiological stress system. As a result, a disturbed balance between glucocorticoid and inflammatory signaling pathways may give rise to a pathological cytokine-induced sickness response that may be the final common pathway underlying central CFS symptoms, i.e. effort/stress intolerance and pain hypersensitivity.

This comprehensive hypothesis on HPA axis hypofunction in CFS may stimulate diagnostic refinement of the illness, inform treatment approaches and suggest directions for future research, particularly focusing on the neuroendocrine-immune interface and possible links between CFS, early and recent life stress, and depression.

 

Source: Van Houdenhove B, Van Den Eede F, Luyten P. Does hypothalamic-pituitary-adrenal axis hypofunction in chronic fatigue syndrome reflect a ‘crash’ in the stress system? Med Hypotheses. 2009 Jun;72(6):701-5. doi: 10.1016/j.mehy.2008.11.044. Epub 2009 Feb 23. https://www.ncbi.nlm.nih.gov/pubmed/19237251

 

Can sustained arousal explain the Chronic Fatigue Syndrome?

Abstract:

We present an integrative model of disease mechanisms in the Chronic Fatigue Syndrome (CFS), unifying empirical findings from different research traditions. Based upon the Cognitive activation theory of stress (CATS), we argue that new data on cardiovascular and thermoregulatory regulation indicate a state of permanent arousal responses – sustained arousal – in this condition.

We suggest that sustained arousal can originate from different precipitating factors (infections, psychosocial challenges) interacting with predisposing factors (genetic traits, personality) and learned expectancies (classical and operant conditioning).

Furthermore, sustained arousal may explain documented alterations by establishing vicious circles within immunology (Th2 (humoral) vs Th1 (cellular) predominance), endocrinology (attenuated HPA axis), skeletal muscle function (attenuated cortical activation, increased oxidative stress) and cognition (impaired memory and information processing). Finally, we propose a causal link between sustained arousal and the experience of fatigue.

The model of sustained arousal embraces all main findings concerning CFS disease mechanisms within one theoretical framework.

 

Source: Wyller VB, Eriksen HR, Malterud K. Can sustained arousal explain the Chronic Fatigue Syndrome? Behav Brain Funct. 2009 Feb 23;5:10. doi: 10.1186/1744-9081-5-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654901/ (Full article)

 

The lifestyle of patients with chronic fatigue syndrome and the effect on fatigue and functional impairments

Abstract:

BACKGROUND: Little is known about the lifestyle of patients with chronic fatigue syndrome (CFS) and its influence on symptoms of CFS. The present study aimed to investigate the lifestyle of patients with CFS, and to assess whether lifestyle factors are related to fatigue and functional impairments.

METHODS: Two hundred and forty-seven patients fulfilling the Center for Disease Control criteria for CFS were included. Validated questionnaires were used to collect data on lifestyle factors, smoking, intake of alcohol, fat, fibres, fruit and vegetables, body mass index (BMI), fatigue severity and functional impairments.

RESULTS: Of the CFS patients, 23% smoked, 32% had an unhealthy BMI, and none had an unhealthy alcohol intake. A majority had an unhealthy food intake: 70% had unhealthy fat, fruit and vegetable intake, and 95% had unhealthy fibre intake. Compared with the general Dutch population, significantly fewer CFS patients were overweight. Significantly more female CFS patients abstained from alcohol, and fewer male CFS patients smoked. Unhealthy lifestyle factors were not significantly associated with fatigue severity or functional impairments.

CONCLUSIONS: CFS patients tend to lead a healthier lifestyle compared to the general Dutch population. However, no relationship was found between lifestyle factors and fatigue severity and functional impairments in CFS.

 

Source: Goedendorp MM, Knoop H, Schippers GM, Bleijenberg G. The lifestyle of patients with chronic fatigue syndrome and the effect on fatigue and functional impairments. J Hum Nutr Diet. 2009 Jun;22(3):226-31. doi: 10.1111/j.1365-277X.2008.00933.x. Epub 2009 Feb 17. https://www.ncbi.nlm.nih.gov/pubmed/19226353

 

Cognitive-behavior therapy in chronic fatigue syndrome: is improvement related to increased physical activity?

Abstract:

This multiple case study of cognitive-behavioral treatment (CBT) for chronic fatigue syndrome (CFS) compared self-report and behavioral outcomes. Eleven relatively high-functioning participants with CFS received 6-32 sessions of outpatient graded-activity oriented CBT.

Self-report outcomes included measures of fatigue impact, physical function, depression, anxiety, and global change. Behavioral outcomes included actigraphy and the 6-minute walking test. Global change ratings were very much improved (n=2), much improved (n=2), improved (n=5), and no change (n=2).

Of those reporting improvement, clinically significant actigraphy increases (n=3) and decreases (n=4) were found, as well as no significant change (n=2). The nature of clinical improvement in CBT trials for high-functioning CFS patients may be more ambiguous than that postulated by the cognitive-behavioral model.

 

Source: Friedberg F, Sohl S. Cognitive-behavior therapy in chronic fatigue syndrome: is improvement related to increased physical activity? J Clin Psychol. 2009 Apr;65(4):423-42. doi: 10.1002/jclp.20551. https://www.ncbi.nlm.nih.gov/pubmed/19213007

 

Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations

Abstract:

Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities. The aim of this study was to explore the protective effects of antidepressants in an animal model of CFS in mice. Male albino mice were forced to swim individually for a period of 6-min session each for 7 days. Imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg) and citalopram (5 and 10 mg/kg) were administered 30 min before forced swimming test on each day.

Various behavior tests (immobility time, locomotor activity, anxiety-like behavior by plus maze and mirror chamber) followed by biochemical parameters (lipid peroxidation, reduced glutathione, catalase and nitrite level) were assessed in chronic stressed mice. Chronic forced swimming for 7 days significantly caused increase in immobility period, impairment in locomotor activity, anxiety-like behavior, and oxidative stress (raised lipid peroxidation, nitrite activity and reduced glutathione and catalase activity) as compared with naïve mice (P < 0.05).

Seven days of pretreatment with imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg), and citalopram (5 and 10 mg/kg) significantly reduced immobility time, improved locomotor activity and anti-anxiety effect (in both plus maze and mirror chamber test), and attenuated oxidative stress in chronic stressed mice as compared with control (chronic fatigues) (P < 0.05). These results suggested that these drugs have protective effect and could be used in the management of chronic fatigue like conditions.

 

Source: Kumar A, Garg R. Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations. Fundam Clin Pharmacol. 2009 Feb;23(1):89-95. doi: 10.1111/j.1472-8206.2008.00638.x. Epub 2009 Jan 10. https://www.ncbi.nlm.nih.gov/pubmed/19207541