Tag: 2009

Chronic fatigue syndrome: a psychoneuroimmunological perspective

Abstract:

This article casts light on the contribution that psychoneuroimmunology can make in the search for the cause of chronic fatigue syndrome (cfs). Several studies suggest that psychosocial and physical stress may play an important predisposing, precipitating and perpetuating role in cfs. Moving on from these studies we now discuss recent research into the stress-related pathophysiological mechanisms of the illness. Although there is evidence for a hypofunctional stress response, a hyperactive immune response and disturbances in the interaction between both, the findings are not consistent. Longitudinal studies are needed to unravel the pathophysiology of cfs still further. In such studies the concept of ‘sickness response’ and ‘sickness behaviour’ may perform an important heuristic function.

 

Source: van Houdenhove B, Heijnen CJ. Chronic fatigue syndrome: a psychoneuroimmunological perspective. Tijdschr Psychiatr. 2009;51(8):603-10. [Article in Dutch] http://www.tijdschriftvoorpsychiatrie.nl/en/issues/413/articles/2821 (Full article)

 

Autoantibodies to lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) in children with chronic nonspecific complaints and with positive antinuclear antibodies

Abstract:

Autoimmune fatigue syndrome (AIFS) is characterized by chronic nonspecific complaints, consistently positive antinuclear antibodies (ANA), and lack of alternate medical explanations. A newly recognized antibody, named anti-Sa, was detected in approximately 40% of the patients by Western blot (WB) using HeLa extract.

Some patients with AIFS later develop chronic fatigue syndrome (CFS), and most of them are positive for anti-Sa. On the other hand, Muro et al. reported anti-DFS70 in patients with CFS. Anti-Sa and anti-DFS70 were turned out to be same specificities by exchanging studies of blind sera. The target antigen of anti-DFS70 was identified as lens epithelium derived growth factor/transcription co-activator p75 (LEDGF/p75).

The objectives of this study are to confirm whether the target antigen of anti-Sa is also LEDGF/p75, and to develop ELISA system by using recombinant protein. Recombinant protein of LEDGF/p75 was purchased from Protein One (Bethesda, MD, USA). We developed an ELISA system to detect anti-LEDGF/p75 by coating this recombinant protein. 226 sera of AIFS patients (including 36 CFS patients) were applied to this ELISA assay and Western immunoblot, and it was revealed that anti-Sa-positive sera defined by WB and sera positive for anti-LEDGF/p75 on ELISA were identical.

Moreover, reactivities of anti-Sa on WB were inhibited by pre-incubating with recombinant LEDGF/p75, and eluted antibodies from the nitrocellulose membrane could react on the ELISA. These results confirm that the Sa antigen is LEDGF/p75. The ELISA assay using recombinant LEDGF/p75 could be a promising tool for measuring anti-Sa and consequently for diagnosing CFS.

 

Source: Kuwabara N, Itoh Y, Igarshi T, Fukunaga Y. Autoantibodies to lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) in children with chronic nonspecific complaints and with positive antinuclear antibodies. Autoimmunity. 2009 Sep;42(6):492-6. Doi: 10.1080/08916930902736663. https://www.ncbi.nlm.nih.gov/pubmed/19657776

 

Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects

Abstract:

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become markedly worse after exercise. Previous studies implicated dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in CFS and FMS.

We recently demonstrated that acid sensing ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These molecular receptors are found on human leukocytes along with SNS and IS genes.

Real-time, quantitative PCR showed that 19 CFS patients had lower expression of beta-2 adrenergic receptors but otherwise did not differ from 16 control subjects before exercise. After a sustained moderate exercise test, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha-2A, beta-1, beta-2, and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05). These increases were also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of physical fatigue, mental fatigue, and pain.

These new findings suggest dysregulation of metabolite detecting receptors as well as SNS and IS in CFS and CFS-FMS.

PERSPECTIVE: Muscle fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and CFS-FMS patients show enhanced gene expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these symptoms. These findings suggest possible new causes, points for intervention, and objective biomarkers for these disorders.

 

Source: Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain. 2009 Oct;10(10):1099-112. doi: 10.1016/j.jpain.2009.06.003. Epub 2009 Jul 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/ (Full article)

 

Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence

Abstract:

Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue.

On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta).

Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome.

 

Source: Sachdeva AK, Kuhad A, Tiwari V, Chopra K. Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence. Behav Brain Res. 2009 Dec 28;205(2):414-20. doi: 10.1016/j.bbr.2009.07.020. Epub 2009 Jul 28. https://www.ncbi.nlm.nih.gov/pubmed/19643148

 

Cardiac function fluctuates during exacerbation and remission in young adults with chronic fatigue syndrome and “small heart”

Abstract:

BACKGROUND: “Small heart syndrome”, previously referred to as so-called “neurocirculatory asthenia” associated with a small heart shadow on the chest roentgenogram, is characterized by weakness or fatigue even after mild exertion, palpitation, dyspnea, and fainting, many of which resemble symptoms in patients with chronic fatigue syndrome (CFS).

METHODS AND RESULTS: The study population comprised 42 patients with CFS younger than 40 years of age. Cardiothoracic ratio was determined on the chest roentgenogram and echocardiographic examination was performed to evaluate both the cardiac chamber size and function. “Small heart” (cardiothoracic ratio < or = 42%) on the chest X-ray photograph was noted in 26 (62%) of the study CFS patients. Echocardiographic examination demonstrated significantly smaller mean values of both the left ventricular (LV) end-diastolic and end-systolic dimensions, stroke volume indexes and cardiac indexes in CFS patients with “small heart” than in those without it and also in 20 control subjects. Thus, CFS patients with “small heart” had an actually small LV chamber and poor cardiac performance. During a long follow-up period of 10 CFS patients with “small heart”, all echocardiographic parameters mentioned above improved and cardiothoracic ratios increased significantly during the remission phase as compared with exacerbation phase.

CONCLUSIONS: “Small heart” on the chest X-ray photograph was prevalently noted in CFS patients. Echocardiographic examination revealed that CFS patients with “small heart” had an actually small LV chamber and poor cardiac performance. Cardiac functional changes evaluated by repeated examinations appeared to be directly associated with the severity of their symptoms. Small heart syndrome with impaired cardiac function may contribute to the development of CFS through low cardiac output as a constitutional factor.

 

Source: Miwa K, Fujita M. Cardiac function fluctuates during exacerbation and remission in young adults with chronic fatigue syndrome and “small heart”. J Cardiol. 2009 Aug;54(1):29-35. doi: 10.1016/j.jjcc.2009.02.008. Epub 2009 Mar 28. http://www.journal-of-cardiology.com/article/S0914-5087(09)00066-5/fulltext (Full article)

 

Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine if self-reported levels of physical activity and fatigue are related to peak oxygen uptake (VO(2peak)) and whether these relationships differ among the patient groups (rheumatoid arthritis [RA], polymyositis [PM], and chronic fatigue syndrome [CFS]).

DESIGN: Correlational investigation.

SETTING: Two ambulatory research clinics at the National Institutes of Health, Clinical Center, Bethesda, MD.

PARTICIPANTS: There were 9 patients with PM, 10 with RA, and 10 with CFS. All patients met case criteria for their respective diagnoses. METHODS/MAIN OUTCOME MEASUREMENTS: VO(2peak) during bicycle ergometry and self-reported fatigability, fatigue, and physical activity. VO(2peak) was used as the criterion measurement of physiological fatigue with which the self-reported variables were compared.

RESULTS: The Pearson r revealed that self-reported physical activity correlated with VO(2peak) (r = 61, P = .01). However, fatigability and fatigue did not correlate with VO(2peak). Linear regression analysis was performed to assess the effects of diagnosis group, self-reported activity level or fatigue, and their interaction. A trend in the data showed a distinctive relationship between fatigue/fatigability within the 3 groups. In addition, when controlling for group status, self-reported activity predicted aerobic capacity as measured by VO(2peak).

CONCLUSIONS: This study confirms that patients with chronic, but stable RA, PM, or CFS are fatigued and have significantly decreased aerobic capacity. Self-reports of physical activity predicted VO(2peak), and may be used as an indicator of activity-based aerobic capacity. Self-reports of fatigue, however, did not correlate with VO(2peak) and hence are assessing something other than an index of aerobic capacity, and provide additional information about patients’ perceptions, which will require further investigation.

 

Source: Weinstein AA, Drinkard BM, Diao G, Furst G, Dale JK, Straus SE, Gerber LH. Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome. PM R. 2009 Jul;1(7):620-8. doi: 10.1016/j.pmrj.2009.04.007. https://www.ncbi.nlm.nih.gov/pubmed/19627955

 

The role of coping in the relationship between depression and illness severity in chronic fatigue syndrome

Abstract:

The self-regulatory model (SRM) proposes that both cognitive and emotional illness representations influence the coping processes adopted in response to an illness.

AIM: This study used the SRM to explore the role of coping in the relationship between depression and self-appraisals of illness severity in a population of patients with chronic fatigue syndrome (CFS).

METHODS: The sample comprised 156 participants, 34 men and 121 women, aged between 18 and 78 yrs, who had been medically diagnosed with CFS. Participants were asked to complete three questionnaires: the Cardiac Depression Scale, Ways of Coping Questionnaire, and Severity Subscale of the Illness Perceptions Questionnaire-Revised.

RESULTS: Analyses revealed that almost 70% of the participants were moderately or severely depressed. Additionally, two particular subscales, social support seeking and positive reappraisals, emerged as positively contributing to self-appraisals of illness severity (beta = 0.20 [p < 0.05] and beta = 0.21 [p < 0.05], respectively), thereby supporting the SRM. Furthermore, results indicated that a combination of depression and coping was a better predictor of illness severity than depression alone, accounting for 22% of the variance compared with 8%, respectively.

CONCLUSIONS: The findings suggest that focusing on depression, and particularly coping styles, during treatment interventions could have important implications for therapeutic interventions. This could lead to better treatment strategies for health professionals who work with patients with CFS.

 

Source: Walker K, Lindner H, Noonan M. The role of coping in the relationship between depression and illness severity in chronic fatigue syndrome. J Allied Health. 2009 Summer;38(2):91-9. https://www.ncbi.nlm.nih.gov/pubmed/19623790

 

Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome

Abstract:

Examination of anticardiolipin antibodies (ACAs) in the sera of patients clinically diagnosed with chronic fatigue syndrome (CFS) using an enzyme-linked immunoassay procedure demonstrated the presence of immunoglobulin M isotypes in 95% of CFS serum samples tested. The presence of immunoglobulin G and immunoglobulin A isotypes were also detected in a subset of the samples. Future studies will focus on elucidating whether alterations to mitochondrial inner membranes and/or metabolic functions play a possible role in the expression of ACAs.

 

Source: Hokama Y, Campora CE, Hara C, Kuribayashi T, Le Huynh D, Yabusaki K. Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome. J Clin Lab Anal. 2009;23(4):210-2. doi: 10.1002/jcla.20325. https://www.ncbi.nlm.nih.gov/pubmed/19623655

 

Use of medications by people with chronic fatigue syndrome and healthy persons: a population-based study of fatiguing illness in Georgia

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating condition of unknown etiology and no definitive pharmacotherapy. Patients are usually prescribed symptomatic treatment or self-medicate. We evaluated prescription and non-prescription drug use among persons with CFS in Georgia and compared it to that in non-fatigued Well controls and also to chronically Unwell individuals not fully meeting criteria for CFS.

METHODS: A population-based, case-control study. To identify persons with possible CFS-like illness and controls, we conducted a random-digit dialing telephone screening of 19,807 Georgia residents, followed by a detailed telephone interview of 5,630 to identify subjects with CFS-like illness, other chronically Unwell, and Well subjects. All those with CFS-like illness (n = 469), a random sample of chronically Unwell subjects (n = 505), and Well individuals (n = 641) who were age-, sex-, race-, and geographically matched to those with CFS-like illness were invited for a clinical evaluation and 783 participated (48% overall response rate). Clinical evaluation identified 113 persons with CFS, 264 Unwell subjects with insufficient symptoms for CFS (named ISF), and 124 Well controls; the remaining 280 subjects had exclusionary medical or psychiatric conditions, and 2 subjects could not be classified. Subjects were asked to bring all medications taken in the past 2 weeks to the clinic where a research nurse viewed and recorded the name and the dose of each medication.

RESULTS: More than 90% of persons with CFS used at least one drug or supplement within the preceding two weeks. Among users, people with CFS used an average of 5.8 drugs or supplements, compared to 4.1 by ISF and 3.7 by Well controls. Persons with CFS were significantly more likely to use antidepressants, sedatives, muscle relaxants, and anti-acids than either Well controls or the ISF group. In addition, persons with CFS were significantly more likely to use pain-relievers, anti-histamines and cold/sinus medications than were Well controls.

CONCLUSION: Medical care providers of patients with chronic fatigue syndrome should be aware of polypharmacy as a problem in such patients, and the related potential iatrogenic effects and drug interactions.

 

Source: Boneva RS, Lin JM, Maloney EM, Jones JF, Reeves WC. Use of medications by people with chronic fatigue syndrome and healthy persons: a population-based study of fatiguing illness in Georgia. Health Qual Life Outcomes. 2009 Jul 20;7:67. doi: 10.1186/1477-7525-7-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731740/ (Full article)

 

Chronic fatigue syndrome in adolescents: do parental expectations of their child’s intellectual ability match the child’s ability?

Abstract:

OBJECTIVE: This cross-sectional study aimed to measure the discrepancy between actual and perceived IQ in a sample of adolescents with CFS compared to healthy controls. We hypothesized that adolescents with CFS and their parent would have higher expectations of the adolescent’s intellectual ability than healthy adolescents and their parent.

METHODS: The sample was 28 CFS patients and 29 healthy controls aged 11-19 years and the parent of each participant. IQ was assessed using the AH4 group test of general intelligence and a self-rating scale which measured perceived IQ.

RESULTS: Parents’ perceptions of their children’s IQ were significantly higher for individuals with CFS than healthy controls.

CONCLUSIONS: High expectations may need to be addressed within the context of treatment.

 

Source: Godfrey E, Cleare A, Coddington A, Roberts A, Weinman J, Chalder T. Chronic fatigue syndrome in adolescents: do parental expectations of their child’s intellectual ability match the child’s ability? J Psychosom Res. 2009 Aug;67(2):165-8. doi: 10.1016/j.jpsychores.2009.02.004. Epub 2009 Apr 16. https://www.ncbi.nlm.nih.gov/pubmed/19616144