Tag: 2008

Association of peripheral inflammatory markers with chronic fatigue in a population-based sample

Abstract:

Alterations in the innate immune response may contribute to the pathogenesis of chronic fatigue syndrome (CFS). However, studies have been limited by small sample sizes, use of patients from tertiary care settings, inappropriate selection of controls, and failure to control for confounding demographic, medical and behavioral factors independently associated with immune activity. It is also not known whether specific symptoms account for observed associations between CFS and the innate immune response.

To address these limitations, the current study examined plasma concentrations of high-sensitivity c-reactive protein (hs-CRP), white blood cell count (WBC) and a combined inflammation factor in a large population-based sample. Log-transformed mean plasma concentrations of hs-CRP were increased in subjects with CFS (n=102) and in subjects with unwellness symptoms that did not meet diagnostic criteria for CFS (defined as “insufficient fatigue” [ISF]) (n=240) when compared to subjects who were well (n=115). Log transformed WBC was increased in ISF and was increased at a trend level in CFS. The combined inflammation factor was increased in both CFS and ISF. Subjects with CFS and ISF did not differ on any of the inflammation measures.

In the entire subject population, the physical component summary score (PCS), but not the mental component summary score (MCS), from the Medical Outcomes Study Short Form-36 (SF-36) was negatively associated with each of the inflammation measures. Depressive symptoms were also associated with increased log hs-CRP. After adjustment for age, sex, race, location of residence, BMI, depressive status and immune-modulating medications, subjects classified as ISF continued to demonstrate increased log hs-CRP, WBC and elevations on the inflammation factor when compared to well controls; however, associations between CFS and log hs-CRP and the inflammation factor were no longer statistically significant. After adjustment, PCS score also remained independently associated with each of the inflammation measures.

These findings support a role for innate immune activation in unexplained fatigue and unwellness, but do not suggest that immune activation is specific to CFS.

Comment in: Chronic fatigue syndrome and the immune system: “findings in search of meanings”. [Brain Behav Immun. 2009]

 

Source: Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. 2009 Mar;23(3):327-37. doi: 10.1016/j.bbi.2008.11.005. Epub 2008 Dec 11. https://www.ncbi.nlm.nih.gov/pubmed/19111923

 

Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming

Abstract:

AIM OF THE STUDY: Alteration of immune function may be associated with chronic fatigue syndrome (CFS) and this study reveals the immunoregulatory effect of Astragalus membranaceus flavonoids (AMF).

MATERIALS AND METHODS: CF rats were induced by food intake restriction plus forced swimming for 6 weeks.

RESULTS: An atrophied spleen associated with a significantly decreased spleen/body weight ratio and a reduced spleen cells proliferation was found in CF rats when compared with home cage controls. AMF given orally at 20, 50 and 100 mg/kg body weight once a day consecutively for 6 weeks could recover the reduced cell proliferation. A switch to Th1-dominated immune regulation was observed in CF rats as the cultured splenocytes produced more interleukin-2 (IL-2) but less IL-4 when compared with controls. Supplementation with AMF could significantly counteract the aberrant cytokine production and rats received AMF exhibited higher endurance capacity to swim when compared with those without AMF administration. Checking the spectrum signals confirmed that the three major isoflavones contained in AMF were ononin, formononetin, and demethylhomopterocarpin.

CONCLUSION: Alterations of immune function may be associated with CFS and the tonic effects of AMF against CF may be attributable to balance the abnormal cytokine level by isoflavones.

 

Source: Kuo YH, Tsai WJ, Loke SH, Wu TS, Chiou WF. Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming. J Ethnopharmacol. 2009 Feb 25;122(1):28-34. doi: 10.1016/j.jep.2008.11.025. Epub 2008 Dec 6. https://www.ncbi.nlm.nih.gov/pubmed/19103273

 

Longitudinal change in chronic fatigue syndrome: what home-based assessments reveal

Abstract:

The purpose of this 2-year prospective study was to compare standard self-report and ecologically-based outcome measures in patients with chronic fatigue syndrome (CFS). Standard measures assessed physical function, fatigue impact, psychological variables, and global impression of change ratings. Ecological measures included actigraphy, a structured activity record, and an electronic fatigue/energy diary.

Results for this high functioning sample (N = 75) revealed that self-report global improvement was significantly associated with lower momentary fatigue and fatigue impact, and a higher frequency of standing up (at home), but not with actigraphy or psychological variables. However, actigraphy change was significantly correlated with change in self-report physical function. At follow-up, only a small minority (<20%) scored in the healthy adult range for fatigue impact and physical function.

The findings suggest that home-based measures of symptom severity and physical functioning may provide evidence of change (or lack of change) that is important for interpreting standard self-report outcomes in CFS.

 

Source: Friedberg F, Sohl SJ. Longitudinal change in chronic fatigue syndrome: what home-based assessments reveal. J Behav Med. 2009 Apr;32(2):209-18. doi: 10.1007/s10865-008-9189-9. Epub 2008 Dec 20. https://www.ncbi.nlm.nih.gov/pubmed/19101789

 

Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG) frequencies in monozygotic twins discordant for chronic fatigue syndrome.

METHODS: Thirteen pairs of female twins underwent polysomnography. During the first night, they adapted to the sleep laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was conducted on sleep electroencephalographic records according to standard criteria, and power spectral analysis was used to quantify delta through beta frequency bands, processed in 6-s blocks. Data were averaged across sleep stage within each twin and coded for sleep stage and the presence or absence of chronic fatigue syndrome (CFS). A completely within-subjects repeated measure multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs.

RESULTS: No significant differences in spectral power in any frequency band were found between those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects genetic influences on the sleep electroencephalogram rather than disease-specific sleep pathology.

CONCLUSIONS: The genetic influences on sleep polysomnography and microarchitecture appear to be stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms that probe sleep regulation may provide a better description of sleep abnormalities in CFS.

 

Source: Armitage R, Landis C, Hoffmann R, Lentz M, Watson N, Goldberg J, Buchwald D. Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome. J Psychosom Res. 2009 Jan;66(1):51-7. doi: 10.1016/j.jpsychores.2008.08.004. Epub 2008 Nov 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634600/ (Full article)

 

Does depression mediate the relation between fatigue severity and disability in chronic fatigue syndrome sufferers?

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is often associated with significant levels of disability. Although fatigue and depression have been found to be independently related to severity of disability, it is not clear how these three factors are mutually related. The present study sought to address this issue by specifically testing a model of mediation whereby depression was hypothesized to influence relations between fatigue and disability.

METHODS: Participants included 90 individuals seeking treatment for CFS at a tertiary care facility. Each provided demographic information and completed standardized measures of depression and fatigue severity, as well as a measure of disability, which assessed difficulties in physical, psychosocial, and independence domains.

RESULTS: Analyses indicated that depression and fatigue were positively correlated with one another, as well as all three disability domains. Analyses of mediation indicated that depression completely mediated the relation between fatigue and psychosocial disability and partially mediated the relation between fatigue and the other two disability domains. Indirect effects tests indicated that the inclusion of depression in the statistical models was statistically meaningful.

CONCLUSIONS: These results replicate previous findings that fatigue and depression are independently related to disability in those with CFS. A more complex statistical model, however, suggested that depression severity substantially influenced the strength of the relation between fatigue and disability levels across a range of domains, including complete mediation in areas involving psychosocial functioning. These results may aid in clarifying contemporary conceptualizations of CFS and provide guidance in the identification of appropriate treatment targets.

 

Source: Hadlandsmyth K, Vowles KE. Does depression mediate the relation between fatigue severity and disability in chronic fatigue syndrome sufferers? J Psychosom Res. 2009 Jan;66(1):31-5. doi: 10.1016/j.jpsychores.2008.08.002. Epub 2008 Nov 22. https://www.ncbi.nlm.nih.gov/pubmed/19073290

 

Chronic fatigue syndrome and DSM-IV personality disorders

Abstract:

OBJECTIVE: Personality is an important factor in the research of the chronic fatigue syndrome (CFS). Although some studies report a high rate of personality disorders–around the 40% level–in samples of patients with CFS, the generalizability of these findings can be questioned. The present study evaluates the prevalence of Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) personality disorders in a sample of female CFS patients and in two control groups.

METHOD: The ADP-IV questionnaire (Assessment of DSM Personality Disorders IV) was used to assess the DSM-IV-TR personality disorders at a dimensional and categorical level in a sample of 50 female CFS patients and in two matched control samples of Flemish civilians (n=50) and psychiatric patients (n=50).

RESULTS: The results indicate a striking lack of statistical significant differences between the CFS sample and the Flemish control group at the level of dimensional Trait scores, number of criteria, and prevalence rates of personality disorder diagnoses. Unsurprisingly, higher scores at these levels were obtained within the psychiatric sample. The prevalence of an Axis II disorder was 12% in the Flemish and CFS samples, whereas the psychiatric sample obtained a prevalence of 54%.

CONCLUSION: The prominent absence of any significant difference in personality disorder characteristics between the female Flemish general population and the CFS samples seems to suggest only a minor etiological role for personality pathology, as defined by the DSM-IV Axis II, within CFS.

 

Source: Courjaret J, Schotte CK, Wijnants H, Moorkens G, Cosyns P. Chronic fatigue syndrome and DSM-IV personality disorders. J Psychosom Res. 2009 Jan;66(1):13-20. doi: 10.1016/j.jpsychores.2008.07.001. Epub 2008 Nov 22. https://www.ncbi.nlm.nih.gov/pubmed/19073288

 

Nitric oxide modulation mediates the protective effect of trazodone in a mouse model of chronic fatigue syndrome

Abstract:

The present study was conducted with the aim of elucidating the possible role of nitric oxide (NO) in the neuroprotective effects of trazodone used to treat chronic fatigue syndrome (CFS) in mice.

Male albino mice were forced to swim for a six minute session each day for 7 days and the immobility period was recorded every other day. Trazodone (5 mg/kg and 10 mg/kg) was administered each day 30 min before the forced swim test. In addition, L-arginine (100 mg/kg) and L-NAME (5 mg/kg) were administered 15 min before administration of trazodone (5 mg/kg).

Various behavioral tests, including locomotor (actophotometer) and anxiety (mirror chamber and plus maze) tests, as well as biochemical parameters (lipid peroxidation, reduced glutathione, catalase, and nitrites) were evaluated on the 8th day.

Forced swimming for 7 days caused a chronic fatigue-like condition, anxiety-like behavior, impairments in locomotor activity, and oxidative damage (increased lipid peroxidation and nitrite levels, and depletions in the reduced forms of glutathione and catalase activity) in animals. Pretreatment with L-NAME (5 mg/kg) potentiated the antioxidant effect of trazodone (5 mg/kg). However, L-arginine (100 mg/kg) pretreatment reversed the protective effect of trazodone (5 mg/kg) (p<0.05). The present study suggests the possible involvement of NO signaling in the protective effect of trazodone.

 

Source: Kumar A, Garg R, Kumar P. Nitric oxide modulation mediates the protective effect of trazodone in a mouse model of chronic fatigue syndrome. Pharmacol Rep. 2008 Sep-Oct;60(5):664-72. http://www.if-pan.krakow.pl/pjp/pdf/2008/5_664.pdf (Full article)

 

Assessment of fibromyalgia & chronic fatigue syndrome: a new protocol designed to determine work capability–chronic pain abilities determination (CPAD)

Abstract:

The objective was to design a protocol to assess work ability in people suffering ill-defined painful and disabling disorders, the outstanding prototype of which is fibromyalgia/chronic fatigue syndrome (FM/CSF).Following an extensive literature search, the mos appropriate components of current methods of assessment of physical and cognitive abilities were incorporated into the protocol, occasionally with appropriate modification to suit the specific requirements of the individual.

The initial part of the assessment consists of a standard history taking, principally focusing on the patient’s self-reported physical and cognitive abilities and disabilities, as well as the completion of established pain and fatigue scales, and relevant disability questionnaires.

Following this, physical and cognitive abilities are objectively assessed on two separate occasions, utilizing computerized hand-held dynamometers, inclinometers, algometers, and force dynamometers. Specific work simulation tests using the industrial standards Methods-Time-Measurement testing are availed of, as is aerobic testing using the Canadian Aerobic Fitness Test (CAFT). Objective computerised neuro-cognitive testing are also utilised as an integral component of the assessment. All results are then subject to specific computerized analysis and compared to normative and standardised work-based databases.

The designed system produces reliable, consistent and reproducible results. It also proves capable of detecting any inconsistencies in patient input and results, in addition to being independent of any possible assessor bias. A new protocol has been designed to determine the working capability of individuals who suffer from various chronic disabling conditions, and represents a significant step forward in a difficult but rapidly expanding area of medical practice.

 

Source: Kelly M, Gagne R, Newman JD, Olney C, Gualtieri C, Trail D. Assessment of fibromyalgia & chronic fatigue syndrome: a new protocol designed to determine work capability–chronic pain abilities determination (CPAD). Ir Med J. 2008 Oct;101(9):277-8. https://www.ncbi.nlm.nih.gov/pubmed/19051616

 

Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls

Abstract:

PURPOSE: Since physical exertion is known to exacerbate the symptoms of chronic fatigue syndrome (CFS) and metabolic changes and including oxidative stress can modulate heat shock protein (HSP) expression responses, we sought to determine whether HSP expression is altered in CFS patients before and after exercise. Heat shock proteins (HSPs) in peripheral blood mononuclear cells (PBMC) were examined from 6 chronic fatigue syndrome (CFS) patients and 7 controls before and after a standardized treadmill exercise. Basal hsp27 was significantly higher among CFS patients compared to controls, and decreased immediately post-exercise, remaining below basal levels even at 7 days. A similar pattern was observed for HSP60, which gradually decreased in CFS patients but increased in controls post-exercise. These findings suggest an abnormal adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.

METHODS: HSP27, HSP60, HSP70 and HSP90 expression from 6 CFS patients and 7 age- and sex-matched controls were examined by western blot analysis of peripheral blood mononuclear cells immediately before, after, and at 1 day and 7 days following a standardized treadmill exercise.

RESULTS: Basal HSP27 was higher among CFS patients than in controls (0.54 +/- 0.13 vs. 0.19 +/- 0.06, mean +/- SEM; P < 0.01). In addition, these levels in CFS patients decreased immediately post-exercise (0.25 +/- 0.09; P < 0.05) and remained below basal levels at day 1 post-exercises (0.18 +/- 0.05; P < 0.05). P < 0.05). This declining expression of HSP27 during the post-exercise period among CFS patients was confirmed by one-way ANOVA analysis with repeated measures (P < 0.05). In contrast, HSP27 levels remained relatively constant following exercise among control subjects. Similar patterns of declining HSP levels in CFS patients were also observed for HSP60 (0.94 +/- 0.40 vs. 1.32 +/- 0.46; P < 0.05), and for HSP90 (0.34 +/- 0.09 vs. 0.49 +/- 0.10; P < 0.05) at day 7 post-exercise compared with basal levels, respectively. In contrast, HSP60 levels in control subjects increased at day 1 (1.09 +/- 0.27) and day 7 (1.24 +/- 0.50) post-exercise compared to corresponding levels immediately post-exercise (0.55 +/- 0.06) (P < 0.05, respectively).

CONCLUSION: These preliminary findings suggest an abnormal or defective adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.

 

Source: Thambirajah AA, Sleigh K, Stiver HG, Chow AW. Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls. Clin Invest Med. 2008 Dec 1;31(6):E319-27. https://www.ncbi.nlm.nih.gov/pubmed/19032901

 

Are patients with chronic fatigue syndrome just ‘tired’ or also ‘sleepy’?

Abstract:

It is presently unclear whether chronic fatigue syndrome (CFS) patients exhibit daytime sleepiness in addition to fatigue. Both, fatigue, such as that seen in CFS patients, and excessive daytime sleepiness, such as in sleep apnea-hypopnea syndrome (SAHS), remain poorly understood. Both daytime conditions are generally related to unrefreshing sleep and show affective symptoms. This study’s objective was to contribute to the understanding of the relationship between fatigue and sleepiness in CFS patients not co-morbid for primary sleep or psychiatric disorders.

We compared 16 untreated CFS patients (mean age 32.8, all females) with 13 untreated SAHS (mean age 47.7, all females) patients and 12 healthy controls (mean age 32.2, all females). Objective sleepiness was measured using multiple sleep latency tests (MSLT). Subjective sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Fatigue Severity Scale, respectively. Mean Sleep Latency (SL) on the MSLT was significantly shorter in SAHS patients than in CFS patients and CFS patients showed significantly shorter mean SL than matched controls but within normal range.

Subjective sleepiness was greatest in SAHS patients and subjective fatigue was highest in CFS patients. Affective symptoms showed highest intensities in CFS patients. While higher than the control group on all measures, compared to SAHS, the CFS group had higher subjective fatigue and lower subjective and objective sleepiness. Despite possible overlap in symptoms and signs of both daytime conditions, our data indirectly support the clinical distinction between fatigue and sleepiness.

 

Source: Neu D, Hoffmann G, Moutrier R, Verbanck P, Linkowski P, Le Bon O. Are patients with chronic fatigue syndrome just ‘tired’ or also ‘sleepy’? J Sleep Res. 2008 Dec;17(4):427-31. doi: 10.1111/j.1365-2869.2008.00679.x. Epub 2008 Oct 17. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2869.2008.00679.x/full (Full article)