Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study

Abstract:

BACKGROUND: Studies comparing chronic fatigue syndrome (CFS) and major depressive disorder (MDD) reported similarities as well as differences between the two disorders. However, whereas psychomotor symptoms have been studied extensively in MDD, such research in CFS is more limited. Moreover, the few studies that compared cognitive and motor performance in MDD and CFS yielded inconsistent results. This study hence directly compares fine psychomotor functioning in both syndromes.

METHODS: Thirty-eight patients diagnosed with CFS without a current major depressive episode (MDE), 32 MDD patients with a current MDE and 38 healthy controls performed two computerized copying tasks differing in complexity: a line-copying task that mainly requires motor effort and a figure-copying task requiring additional cognitive efforts. All participants were female. A multivariate general linear model was used to compute group differences.

RESULT: Overall, both patient groups performed more slowly than the controls. Compared to CFS patients, patients with MDD needed significantly more time to copy the single lines but no such between-group performance difference was observed for the figure reproductions. In this latter copying task, the increasing complexity of the figures resulted in prolonged reaction times for all three participant groups with the effect being larger and the magnitude similar for the two patient groups.

LIMITATIONS: All patients were female and most were on psychotropic medication.

CONCLUSIONS: Both the MDD and CFS patients tested demonstrated an overall fine motor slowing, with the motor component being more affected in the MDD patients than in the CFS patients while both patient groups showed similar cognitive impairments.

 

Source: Schrijvers D, Van Den Eede F, Maas Y, Cosyns P, Hulstijn W, Sabbe BG. Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study. J Affect Disord. 2009 May;115(1-2):46-53. doi: 10.1016/j.jad.2008.08.010. Epub 2008 Sep 24. https://www.ncbi.nlm.nih.gov/pubmed/18817977

 

Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome

Abstract:

BACKGROUND: It has been suggested that postural orthostatic tachycardia syndrome (POTS) be considered in the differential diagnosis of those with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Currently, measurement of haemodynamic response to standing is not recommended in the UK NICE CFS/ME guidelines.

OBJECTIVES: To determine prevalence of POTS in patients with CFS/ME.

DESIGN: Observational cohort study.

METHODS: Fifty-nine patients with CFS/ME (Fukuda criteria) and 52 age- and sex-matched controls underwent formal autonomic assessment in the cardiovascular laboratory with continuous heart rate and beat-to-beat blood pressure measurement (Task Force, CNSystems, Graz Austria). Haemodynamic responses to standing over 2 min were measured. POTS was defined as symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of >30 beats per minute or to a heart rate of >120 beats per minute on standing.

RESULTS: Maximum heart rate on standing was significantly higher in the CFS/ME group compared with controls (106 +/- 20 vs. 98 +/- 13; P = 0.02). Of the CFS/ME group, 27% (16/59) had POTS compared with 9% (5) in the control population (P = 0.006). This difference was predominantly related to the increased proportion of those in the CFS/ME group whose heart rate increased to >120 beats per minute on standing (P = 0.0002). Increasing fatigue was associated with increase in heart rate (P = 0.04; r(2) = 0.1).

CONCLUSION: POTS is a frequent finding in patients with CFS/ME. We suggest that clinical evaluation of patients with CFS/ME should include response to standing. Studies are needed to determine the optimum intervention strategy to manage POTS in those with CFS/ME.

 

Source: Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Dec;101(12):961-5. doi: 10.1093/qjmed/hcn123. Epub 2008 Sep 19. http://qjmed.oxfordjournals.org/content/101/12/961.long (Full article)

 

Immunological aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterises unexplained disabling fatigue and a combination of non-specific accompanying symptoms for at least 6 months, in the absence of a medical diagnosis that would otherwise explain the clinical presentation. Other common symptoms include headaches, myalgia, arthralgia, and post-exertional malaise; cognitive difficulties, with impaired memory and concentration; unrefreshing sleep; and mood changes.

Similar disorders have been described for at least two centuries and have been differently named neurasthenia, post-viral fatigue, myalgic encephalomyelitis and chronic mononucleosis. Recent longitudinal studies suggest that some people affected by chronic fatigue syndrome improve with time but that most remain functionally impaired for several years. The estimated worldwide prevalence of CFS is 0.4-1% and it affects over 800,000 people in the United States and approximately 240,000 patients in the UK.

No physical examination signs are specific to CFS and no diagnostic tests identify this syndrome. The pathophysiological mechanism of CFS is unclear. The main hypotheses include altered central nervous system functioning resulting from an abnormal immune response against a common antigen; a neuroendocrine disturbance; cognitive impairment caused by response to infection or other stimuli in sentient people. The current concept is that CFS pathogenesis is a multifactorial condition.

Various studies have sought evidence for a disturbance in immunity in people with CFS. An alteration in cytokine profile, a decreased function of natural killer (NK) cells, a presence of autoantibodies and a reduced responses of T cells to mitogens and other specific antigens have been reported. The observed high level of pro-inflammatory cytokines may explain some of the manifestations such as fatigue and flu-like symptoms and influence NK activity. Abnormal activation of the T lymphocyte subsets and a decrease in antibody-dependent cell-mediated cytotoxicity have been described. An increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR activation markers have been reported, and a decrease in CD11b expression associated with an increased expression of CD28+ T subsets has been observed. This review discusses the immunological aspects of CFS and offers an immunological hypothesis for the disease processes.

 

Source: Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G. Immunological aspects of chronic fatigue syndrome. Autoimmun Rev. 2009 Feb;8(4):287-91. doi: 10.1016/j.autrev.2008.08.003. Epub 2008 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/18801465

 

Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection

Abstract:

The purpose of this study was to evaluate the beneficial effect of Hochu-ekki-to (TJ-41) combined with interferon-gamma (IFN gamma) on daily activity, immunological and neurological alternation in a mouse model of chronic fatigue syndrome (CFS).

CFS was induced by 6 times of repeated injection of Brucella abortus antigen every 2 weeks. Both single TJ-41 and TJ-41 combined with IFN gamma increased running activity and thymus weight of CFS mice, while thicker thymic cortex together with elevation of natural killer cell activity was only found in the combined treatment group. No significant improvement was observed in the atrophic brain and decreased expression level of brain-derived neurotrophic factor and Bcl-2 mRNA in hippocampus in both treatment groups.

Our results suggest that TJ-41 combined with IFN gamma might have a protective effect on the marked reduction in the activity in a model of CFS via normalization of host immune responses, but not neuroprotection.

 

Source: Chen R, Moriya J, Luo X, Yamakawa J, Takahashi T, Sasaki K, Yoshizaki F. Hochu-ekki-to combined with interferon-gamma moderately enhances daily activity of chronic fatigue syndrome mice by increasing NK cell activity, but not neuroprotection. Immunopharmacol Immunotoxicol. 2009 Jun;31(2):238-45. doi: 10.1080/08923970802391525.https://www.ncbi.nlm.nih.gov/pubmed/18791913

 

Anaesthesia for patients with idiopathic environmental intolerance and chronic fatigue syndrome

Abstract:

BACKGROUND: Idiopathic environmental intolerance syndrome (IEI), formerly known as multiple chemical sensitivity syndrome (MCSS), andchronic fatigue syndrome (CFS) are controversial diseases and there is little information in the literature regarding the appropriate conduct of anaesthesia in such patients.

METHODS: We studied 27 patients referred to our anaesthetic allergy clinic with IEI and CFS and performed literature and web searches on anaesthesia in these disorders.

RESULTS: The patients had a significant incidence of adverse events related to anaesthesia which were not allergic in nature. The adverse effects usually occurred postoperatively and were self limiting. Patients with IEI and CFS are not at risk of anaphylaxis and there is no scientific evidence that any drug or technique is excessively hazardous. Neither our patients nor the review of the scientific literature supported available web-based recommendations for the anaesthetic management of patients with IEL and CFS.

CONCLUSIONS: We suggest that the anaesthetist may be best to use the technique they would use if the patient did not have CFS or IEI but avoid drugs to which there is a history of adverse response. Anaesthesia is likely to be associated with adverse effects in these patients but the effects are not likely to be severe. A series of recommendations for the safe and harmonious conduct of anaesthesia in patients with CFS and IEI are provided.

 

Source: Fisher MM, Rose M. Anaesthesia for patients with idiopathic environmental intolerance and chronic fatigue syndrome. Br J Anaesth. 2008 Oct;101(4):486-91. doi: 10.1093/bja/aen242. http://bja.oxfordjournals.org/content/101/4/486.long (Full article)

 

Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: an exploratory analysis

Abstract:

This work investigates the significance of changes in association patterns linking indicators of neuroendocrine and immune activity in patients with chronic fatigue syndrome (CFS). Gene sets preferentially expressed in specific immune cell isolates were integrated with neuroendocrine data from a large population-based study.

Co-expression patterns linking immune cell activity with hypothalamic-pituitary-adrenal (HPA), thyroidal (HPT) and gonadal (HPG) axis status were computed using mutual information criteria. Networks in control and CFS subjects were compared globally in terms of a weighted graph edit distance. Local re-modeling of node connectivity was quantified by node degree and eigenvector centrality measures. Results indicate statistically significant differences between CFS and control networks determined mainly by re-modeling around pituitary and thyroid nodes as well as an emergent immune sub-network.

Findings align with known mechanisms of chronic inflammation and support possible immune-mediated loss of thyroid function in CFS exacerbated by blunted HPA axis responsiveness.

 

Source: Fuite J, Vernon SD, Broderick G. Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: an exploratory analysis. Genomics. 2008 Dec;92(6):393-9. doi: 10.1016/j.ygeno.2008.08.008. Epub 2008 Oct 1. http://www.sciencedirect.com/science/article/pii/S0888754308001948 (Full article)

 

Lower frequency of IL-17F sequence variant (His161Arg) in chronic fatigue syndrome patients

Abstract:

Chronic fatigue syndrome (CFS) is characterized by immune dysfunctions including chronic immune activation, inflammation, and alteration of cytokine profiles. T helper 17 (Th17) cells belong to a recently identified subset of T helper cells, with crucial regulatory function in inflammatory and autoimmune processes. Th17 cells are implicated in allergic inflammation, intestinal diseases, central nervous system inflammation, disorders that may all contribute to the pathophysiology of CFS. IL-17F is one of the pro-inflammatory cytokines secreted by Th17 cells.

We investigated the association between CFS and the frequency of rs763780, a C/T genetic polymorphism leading to His161Arg substitution in the IL-17F protein. The His161Arg variant (C allele) antagonizes the pro-inflammatory effects of the wild-type IL-17F. A significantly lower frequency of the C allele was observed in the CFS population, suggesting that the His161Arg variant may confer protection against the disease. These results suggest a role of Th17 cells in the pathogenesis of CFS.

 

Source: Metzger K, Frémont M, Roelant C, De Meirleir K. Lower frequency of IL-17F sequence variant (His161Arg) in chronic fatigue syndrome patients. Biochem Biophys Res Commun. 2008 Nov 7;376(1):231-3. doi: 10.1016/j.bbrc.2008.08.135. Epub 2008 Sep 5. https://www.ncbi.nlm.nih.gov/pubmed/18774769

 

Functional incapacity and physical and psychological symptoms: how they interconnect in chronic fatigue syndrome

Abstract:

BACKGROUND: It has been argued that perceived functional incapacity might be a primary characteristic of chronic fatigue syndrome (CFS) and could be explained by physical symptoms. If so, it could be expected to be closely associated with physical, but not psychological symptoms. The study tests this hypothesis.

SAMPLING AND METHODS: The sample consisted of 73 patients, with a diagnosis of CFS according to the Oxford criteria, randomly selected from clinics in the Departments of Immunology and Psychiatry at St. Bartholomew’s Hospital, London. The degree of fatigue experienced by patients was assessed using the Chalder Fatigue Questionnaire and a visual analogue scale. Self-rated instruments were used to measure physical and social functioning, quality of life, and physical and psychological symptoms.

RESULTS: Principal-component analysis of all scale scores revealed 2 distinct components, explaining 53% of the total variance. One component was characterized by psychological symptoms and generic quality of life indicators, whilst the other component was made up of physical symptoms, social and physical functioning and indicators of fatigue.

CONCLUSIONS: The findings suggest that perceived functional incapacity is a primary characteristic of CFS, which is manifested and/or explained by physical symptoms.

(c) 2008 S. Karger AG, Basel.

 

Source: Priebe S, Fakhoury WK, Henningsen P. Functional incapacity and physical and psychological symptoms: how they interconnect in chronic fatigue syndrome. Psychopathology. 2008;41(6):339-45. doi: 10.1159/000152375. Epub 2008 Sep 3. https://www.ncbi.nlm.nih.gov/pubmed/18765959

 

Can CBT substantially change grey matter volume in chronic fatigue syndrome?

Sir, I wish to comment on the paper ‘Increase in prefrontal cortical volume following cognitive behavioural therapy (CBT) in patients with chronic fatigue syndrome (CFS)’ (De Lange et al., 2008). The authors compared the grey matter volume (GMV) of 22 patients with CFS before and after treatment with CBT, and with 22 healthy controls who were assessed at a similar time interval but received no treatment. The patient sample at baseline had a 5% smaller GMV as compared to healthy controls. In patients, GMV at baseline was correlated with slow information processing speed and physical activity. At follow-up, in the patient group, mean GMV increased with 0.7% from 669.4 to 674.1 ml. This increase in GMV was correlated with changes in cognitive speed. On the basis of this result, the authors conclude ‘that the cerebral atrophy associated with CFS is partially reversed after effective CBT’. In the Netherlands, a press release of the author’s institution even states ‘CBT brings about structural changes in brains of patients’ (Radboud University, 2008). The question arises whether the study results indeed support such far reaching conclusions.

Two critical points need to be taken into consideration. First, the authors did not include a control group of patients receiving no treatment or a different treatment. Therefore, the increase in GMV cannot be attributed to the CBT treatment given. It is possible that the natural course of and fluctuations in the illness are responsible for this result. In addition, it might be possible that other treatments than CBT would have resulted in the same, or even better, results. Second, even if the results were indeed to be attributed to changes in lifestyle brought about by CBT, several questions still remain. To name a few, first, the increase in volume of <1% is very modest. Therefore, the question is whether, although statistically significant, this small increase is also of clinical significance. Second, if CBT brings about changes in lifestyle, and these changes are responsible for small improvements in the patients’ brain and activity levels, are these changes structural and related to the primary disease process? An alternative interpretation is that changing the lifestyle of patients, influences their quality of life, activity patterns and GMV, while the underlying disease process is not influenced.

Another critical remark relates to the fact that the authors in their paper do not mention the proportion of absolute increase in GMV of 0.7%, but rather report that the initial between-group difference between patients and healthy controls decreases with 12%. For readers, it is important to realize that the measure of change reported by the authors is influenced by the absolute size of the between-group difference: the smaller, and therefore less relevant, this difference is, the larger the reported proportion becomes, thereby making less relevant results looking more impressive.

The above considerations lead to the conclusion, that the author’s results, although interesting, do not support the far reaching conclusions regarding the power of CBT.

You can read the rest of this comment here: http://brain.oxfordjournals.org/content/132/6/e110.long

Comment in: Change in grey matter volume cannot be assumed to be due to cognitive behavioural therapy. [Brain. 2009]

Comment on: Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. [Brain. 2008]

 

Source: Bramsen I. Can CBT substantially change grey matter volume in chronic fatigue syndrome? Brain. 2009 Jun;132(Pt 6):e110; author reply e111. doi: 10.1093/brain/awn207. Epub 2008 Aug 29. http://brain.oxfordjournals.org/content/132/6/e110.long (Full article)

 

Chronic fatigue syndrome with autoantibodies–the result of an augmented adjuvant effect of hepatitis-B vaccine and silicone implant

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) that defines by prolonged fatigue and other manifestations, was recently integrated into a spectrum of central sensitivity syndromes including several diseases as fibromylagia. CFS etiology is multi-factorial commonly triggered by infectious agents. Vaccines, induce an immune response similarly to infections, and may trigger just like infections autoimmune diseases, CFS and fibromyalgia. Furthermore vaccines contain an adjuvant which enhances their immune stimulation.

CASE PRESENTATION: A 56-year-old woman was diagnosed with CFS accompanied by fibromyalgia, demyelination and autoantibodies. Her illness begun following the 2nd dose of hepatitis-B vaccine, and was aggravated by the 3rd vaccination. She underwent silicone breast implantation 6 years before vaccination with no adverse events. However, between the 2nd and 3rd vaccination she suffered a breast injury with local inflammation. Upon explanation of her breast implants silicone leak was observed.

DISCUSSION: Vaccines have been reported to precede CFS mainly following exposure to multiple vaccinations (e.g. the Gulf war syndrome), or as an adverse response to the vaccine adjuvant (e.g. the macrophagic myofasciitis syndrome). Silicone is considered an adjuvant to the immune system, and may induce “the adjuvant disease”. Silicone implant, especially silicone leak relationship with autoimmunity and CFS has been the focus of considerable debates.

CONCLUSION: Our patient illness started following hepatitis-B vaccine, suggesting that it was caused or accelerated by vaccination. In parallel to vaccination our patient suffered from breast injury, which might represent the time of silicone leak. The exposure to the adjuvant, silicone, might have augmented her immune response to the vaccine. To the best of our knowledge this is the first case of combined adverse effect to vaccine and silicone. Vaccine safety in individuals with silicone implants requires further studies.

 

Source: Nancy AL, Shoenfeld Y. Chronic fatigue syndrome with autoantibodies–the result of an augmented adjuvant effect of hepatitis-B vaccine and silicone implant. Autoimmun Rev. 2008 Oct;8(1):52-5. doi: 10.1016/j.autrev.2008.07.026. Epub 2008 Aug 24. https://www.ncbi.nlm.nih.gov/pubmed/18725327