A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome

Abstract:

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been found in a high proportion of chronic fatigue syndrome (CFS) patients and includes enhanced corticosteroid-induced negative feedback, basal hypocortisolism, attenuated diurnal variation, and a reduced responsivity to challenge. A putative causal role for genetic profile, childhood trauma, and oxidative stress has been considered.

In addition, the impact of gender is demonstrated by the increased frequency of HPA axis dysregulation in females. Despite the temporal relationship, it is not yet established whether the endocrine dysregulation is causal, consequent, or an epiphenomenon of the disorder. Nonetheless, given the interindividual variation in the effectiveness of existing biological and psychological treatments, the need for novel treatment strategies such as those which target the HPA axis is clear.

 

Source: Tomas C, Newton J, Watson S. A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. ISRN Neurosci. 2013 Sep 30;2013:784520. doi: 10.1155/2013/784520. eCollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045534/ (Full article)

 

Chronic fatigue syndrome following infections in adolescents

Abstract:

PURPOSE OF REVIEW: To review the recent epidemiology, pathophysiology, and treatment of postinfectious chronic fatigue syndrome (CFS) in adolescents.

RECENT FINDINGS: Thirteen percent of adolescents (mainly women) met the criteria for CFS 6 months following infectious mononucleosis; the figure was 7% at 12 months and 4% at 24 months. Peak work capacity, activity level, orthostatic intolerance, salivary cortisol, and natural killer cell number and function were similar between adolescents with CFS following infectious mononucleosis and recovered controls. Autonomic system, oxygen consumption, peak oxygen pulse, psychological and cytokine network differences were documented between those who recovered and those who did not.

SUMMARY: The prognosis of CFS is better in adolescents than in adults. Activity level, exercise tolerance, and orthostatic testing could not distinguish patients with CFS from adolescents who have recovered from infectious mononucleosis (controls), while certain cytokine network analyses, life stress factors, and autonomic symptoms could.

 

Source: Katz BZ, Jason LA. Chronic fatigue syndrome following infections in adolescents. Curr Opin Pediatr. 2013 Feb;25(1):95-102. doi: 10.1097/MOP.0b013e32835c1108. https://www.ncbi.nlm.nih.gov/pubmed/23263024

 

Association of monoamine-synthesizing genes with the depression tendency and personality in chronic fatigue syndrome patients

Abstract:

AIMS: Tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GCH) are the rate-limiting enzymes for the biosynthesis of catecholamines and tetrahydrobiopterin (BH4), respectively. Since catecholamines and BH4 are thought to be involved in the pathophysiology of CFS, we explored the genetic factors that influence CFS development and examined the possible association between the SNPs of the TH and GCH genes and the various characteristics of CFS patients.

MAIN METHODS: After drawing venous blood from CFS patients and controls, genomic DNA was then extracted from whole blood in accordance with standard procedures. Digestion patterns of the PCR products were used for genotyping the SNPs of GCH (rs841; C+243T) and TH (rs10770141; C-824T). We also performed questionnaires consisting of fatigue-scale and temperament and character inventory scale (TCI) to CFS patients.

KEY FINDINGS: Our results demonstrated that the allele differences for the GCH and TH SNPs were not associated with CFS patients. We did find that the GCH gene with the C+243T polymorphism affected harm avoidance, while the TH gene with the C-824T polymorphism affected persistence in the CFS patients. The concept of persistence has been linked to specific personality, such as perfectionism, in CFS.

SIGNIFICANCE: Our results suggest that the biosynthetic pathways of the monoamine neurotransmitters that are mediated by TH and GCH might be associated with the CFS clinical findings, because persistence is one of the typical personality traits observed in CFS and patients with major depressive disorder exhibit a higher harm avoidance score.

Copyright © 2012 Elsevier Inc. All rights reserved.

 

Source: Fukuda S, Horiguchi M, Yamaguti K, Nakatomi Y, Kuratsune H, Ichinose H, Watanabe Y. Association of monoamine-synthesizing genes with the depression tendency and personality in chronic fatigue syndrome patients. Life Sci. 2013 Feb 27;92(3):183-6. doi: 10.1016/j.lfs.2012.11.016. Epub 2012 Dec 13. https://www.ncbi.nlm.nih.gov/pubmed/23246742

 

Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a clinical condition characterized by severe and disabling fatigue that is medically unexplained and lasts longer than 6 months. Although it is possible to effectively treat CFS, the nature of the underlying physiology remains unclear. Various studies have sought evidence for an underlying disturbance in immunity. The aim of this study was to compare the humoral and cellular immune responses upon influenza vaccination in CFS patients and healthy controls.

RESULTS: Identical antibody titers were observed in CFS patients and healthy controls. Patients and controls demonstrated similar seroprotection rates against all three virus-strains of the influenza vaccine, both pre- and post-vaccination. Functional T cell reactivity was observed in both CFS patients and healthy controls. CFS patients showed a non-significant, numerically lower cellular proliferation at baseline compared to controls. Vaccination induced a significant increase in cellular proliferation in CFS patients, but not in healthy controls. Cytokine production and the number of regulatory T cells were comparable in patients and controls.

CONCLUSIONS: The humoral and cellular immune responses upon influenza vaccination were comparable in CFS patients and healthy controls. Putative aberrations in immune responses in CFS patients were not evident for immunity towards influenza. Standard seasonal influenza vaccination is thus justified and, when indicated, should be recommended for patients suffering from CFS.

 

Source: Prinsen H, de Vries IJ, Torensma R, Pots JM, Mulder SF, van Herpen CM, Elving LD, Bleijenberg G, Stelma FF, van Laarhoven HW. Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome. BMC Immunol. 2012 Dec 17;13:71. doi: 10.1186/1471-2172-13-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534525/ (Full article)

 

Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a chronic, disabling illness that affects approximately 0.2% of the population. Non-restorative sleep despite sufficient or extended total sleep time is one of the major clinical diagnostic criteria; however, the underlying cause of this symptom is unknown.

This review aims to provide a comprehensive overview of the literature examining sleep in CFS/ME and the issues surrounding the current research findings. Polysomnographic and other objective measures of sleep have observed few differences in sleep parameters between CFS/ME patients and healthy controls, although some discrepancies do exist. This lack of significant objective differences contrasts with the common subjective complaints of disturbed and unrefreshed sleep by CFS/ME patients.

The emergence of new, more sensitive techniques that examine the microstructure of sleep are showing promise for detecting differences in sleep between patients and healthy individuals. There is preliminary evidence that alterations in sleep stage transitions and sleep instability, and other physiological mechanisms, such as heart rate variability and altered cortisol profiles, may be evident. Future research investigating the etiology of non-restorative sleep in CFS/ME may also help us to undercover the causes of non-restorative sleep and fatigue in other medical conditions.

 

Source: Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review. J Clin Sleep Med. 2012 Dec 15;8(6):719-28. doi: 10.5664/jcsm.2276. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501671/ (Full article)

 

Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor

Abstract:

BACKGROUND: Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(-)] autoantibodies.

METHODOLOGY: Five CFS(+) and six CFS(-) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[(11)C]methyl-3-piperidyl benzilate [(11)C](+)3-MPB for the mAChR binding and N-[(11)C]methyl-4-piperidyl acetate [(11)C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [(11)C](+)3-MPB binding in CFS(-) patients did not differ from normal controls, CFS(+) patients showed significantly lower [(11)C](+)3-MPB binding than CFS(-) patients and normal controls. In contrast, the [(11)C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups.

CONCLUSION: The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients.

 

Source: Yamamoto S, Ouchi Y, Nakatsuka D, Tahara T, Mizuno K, Tajima S, Onoe H, Yoshikawa E, Tsukada H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of [11C](+)3-MPB binding in brain of chronic fatigue syndrome with serum autoantibody against muscarinic cholinergic receptor. PLoS One. 2012;7(12):e51515. doi: 10.1371/journal.pone.0051515. Epub 2012 Dec 11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519853/ (Full article)

 

Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit

Abstract:

We report on an audit of 138 ME/CFS patients who attended a private practice and took the ATP Profile biomedical test. The results revealed that all of these patients had measureable mitochondrial dysfunction. A basic treatment regime, based on 1) eating the evolutionary correct stone-age diet, 2) ensuring optimum hours of good quality sleep, 3) taking a standard package of nutritional supplements, and 4) getting the right balance between work and rest, was recommended for all patients. Additions to the basic regime were tailored for each patient according to the results of the ATP Profile and additional nutritional tests and clues from the clinical history.

Mitochondrial function is typically impaired in two ways: substrate or co-factor deficiency, and inhibition by chemicals, exogenous or endogenous. For the former, additional nutrients are recommended where there is a deficiency, and for the latter, improvement of anti-oxidant status and selective chelation therapy or far-infrared saunas are appropriate. We show case histories of nine patients who have taken the ATP Profile on three or four occasions, and a before-and-after treatment summary of the 34 patients who have had at least two ATP Profile tests separated by some months.

Finally, we summarize the results for the 30 patients who followed all aspects of the treatment regime and compare them with the 4 patients who were lax on two or more aspects of the treatment regime. All patients who followed the treatment regime improved in mitochondrial function by on average a factor of 4.

 

Source: Myhill S, Booth NE, McLaren-Howard J. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit. Int J Clin Exp Med. 2013;6(1):1-15. Epub 2012 Nov 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515971/ (Full article)

 

Implementing evidence-based practice for patients with chronic fatigue syndrome

Abstract:

The aim of our study was to explore whether community-based mental health care centres (MHCs) are able to implement and sustain cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) with the help of an implementation manual. We monitored the implementation process and treatment outcome data of three Dutch MHCs that implemented or sustained CBT for CFS, one in the context of a stepped care programme. We compared these data with findings of other treatment studies conducted in the context of CBT for CFS.

All three MHCs included at least 40 patients with dropout rates between 15% and 35% from intention-to-treat to second assessment. Effect sizes ranged between 0.88 and 1.76 for changes in fatigue severity and 0.43 and 1.23 for changes in physical functioning. With one exception, these outcomes were within the range of our benchmark. Contrary to original expectations, we provided additional implementation support to the two MHCs new with CBT for CFS. We concluded that our implementation manual does not seem to substitute external support for team leaders and associated professions during initial implementation of CBT for CFS but may have the potential to make this assistance more efficient. Particular attention should be paid to challenges of implementing stepped care for CFS.

KEY PRACTITIONERS MESSAGE: Implementation of CBT for CFS in community-based MHCs was monitored. External support was provided in addition to an implementation manual during initial implementation of CBT for CFS. Participating MHCs were generally capable of successfully implementing and delivering CBT for CFS. Implementation of low-intensity interventions for CFS might better be postponed until therapists have sufficient experience with conventional CBT for CFS.

Copyright © 2012 John Wiley & Sons, Ltd.

 

Source: Wiborg JF, Wensing M, Tummers M, Knoop H, Bleijenberg G. Implementing evidence-based practice for patients with chronic fatigue syndrome. Clin Psychol Psychother. 2014 Mar-Apr;21(2):108-14. doi: 10.1002/cpp.1827. Epub 2012 Dec 11. https://www.ncbi.nlm.nih.gov/pubmed/23229956

 

Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome

Abstract:

OBJECTIVES: A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.

METHODS: A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.

RESULTS: CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS-D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.

CONCLUSIONS: The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.

© 2013 The Association for the Publication of the Journal of Internal Medicine.

Comment in: Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning. [J Intern Med. 2013]

 

Source: Lewis I, Pairman J, Spickett G, Newton JL. Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome. J Intern Med. 2013 May;273(5):501-10. doi: 10.1111/joim.12022. Epub 2013 Jan 7. http://onlinelibrary.wiley.com/doi/10.1111/joim.12022/full (Full article)

 

Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two “fatigue” syndromes with overlapping symptoms and possibly related aetiologies

Abstract:

In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit.

Today, 20 months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors.

All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview.

Copyright © 2012 Elsevier B.V. All rights reserved.

 

Source: Rovigatti U. Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two “fatigue” syndromes with overlapping symptoms and possibly related aetiologies. Neuromuscul Disord. 2012 Dec;22 Suppl 3:S235-41. doi: 10.1016/j.nmd.2012.10.018. https://www.ncbi.nlm.nih.gov/pubmed/23182646