Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model

Abstract:

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens.

The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels.

These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

 

Source: Gupta A, Vij G, Sharma S, Tirkey N, Rishi P, Chopra K. Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model. Immunobiology. 2009;214(1):33-9. doi: 10.1016/j.imbio.2008.04.003. Epub 2008 Jun 17. https://www.ncbi.nlm.nih.gov/pubmed/19159825

 

Association of chronic fatigue syndrome and acute psychotic episode: is it coincidental?

Sir: We present a case of a woman who had suffered from chronic fatigue syndrome (CFS) for several years and was admitted for an acute psychotic episode. This association has rarely been described.

Case report. Ms. A, a 43-year-old mother of 2 children, was admitted in January 2006 with delusion and hallucinations following a period of exacerbated fatigue. She was afraid that her children would be abducted by the devil and tried to protect them. She begged her children not to get near the walls of her house for fear that the devil could erupt from the walls and take them.

Ms. A first experienced persistent fatigue 3 years before admission. Prior to this, she had been a very active woman. She had to stop working and was able to participate in only very few activities during the day. She attributed her fatigue to the overwhelming task of educating her hyperkinetic 9-year-old son.

She had a depressive episode of several months’ duration 10 years before admission, following an abortion of a pregnancy involving a malformed child. This episode had subsided without relapse. She had infectious mononucleosis 20 years before admission. A polysomnographic test 2 years before admission showed many awakenings interrupting Ms. A’s sleep pattern. She was then diagnosed with chronic fatigue syndrome according to the criteria of Holmes1 and Fukuda.2 Antidepressive medication was prescribed; it alleviated the secondary depressive symptoms but had no impact on her fatigue complaint.

During Ms. A’s hospitalization, her blood analysis results were unremarkable, excluding common organic causes of fatigue. Results of her neurologic examination at admission were normal. Her brain computed tomography (CT) scan showed frontal cortical atrophy, but neuropsychological tests failed to show major cognitive impairments.

Olanzapine was prescribed at the dosage of 15 mg/day, and her symptoms gradually subsided. She was discharged 1 month after admission, totally free of her psychotic symptoms. Her neuroleptic treatment was changed to 10 mg of aripiprazole because of excessive weight gain. Aripiprazole was as effective as olanzapine but allowed her to return to her usual weight. The treatment was gradually stopped after 1 year, with no recurrence of psychotic symptoms.

The association between CFS and psychosis has rarely been described. We are aware of only 2 other case reports. The first describes a 28-year-old man who developed CFS after mononucleosis and suffered afterward from a manic episode with psychotic characteristics.3

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629064/

 

Source: Kornreich C, Szombat M, Vandriette YM, Dan B. Association of chronic fatigue syndrome and acute psychotic episode: is it coincidental? Prim Care Companion J Clin Psychiatry. 2008;10(5):412. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629064/ (Full article)

 

Barriers to healthcare utilization in fatiguing illness: a population-based study in Georgia

Abstract:

BACKGROUND: The purpose of this study was to determine the prevalence of barriers to healthcare utilization in persons with fatiguing illness and describe its association with socio-demographics, the number of health conditions, and frequency of healthcare utilization. Furthermore, we sought to identify what types of barriers interfered with healthcare utilization and why they occurred.

METHODS: In a cross-sectional population-based survey, 780 subjects, 112 of them with chronic fatigue syndrome (CFS), completed a healthcare utilization questionnaire. Text analysis was used to create the emerging themes from verbatim responses regarding barriers to healthcare utilization. Multiple logistic regression was performed to examine the association between barriers to healthcare utilization and other factors.

RESULTS: Forty percent of subjects reported at least one barrier to healthcare utilization. Of 112 subjects with CFS, 55% reported at least one barrier to healthcare utilization. Fatiguing status, reported duration of fatigue, insurance, and BMI were significant risk factors for barriers to healthcare utilization. After adjusting for socio-demographics, medication use, the number of health problems, and frequency of healthcare utilization, fatiguing status remained significantly associated with barriers to healthcare utilization.

Subjects with CFS were nearly 4 times more likely to forego needed healthcare during the preceding year than non-fatigued subjects while those with insufficient fatigue (ISF) were nearly 3 times more likely.Three domains emerged from text analysis on barriers to healthcare utilization: 1) accessibility; 2) knowledge-attitudes-beliefs (KABs); and, 3) healthcare system. CFS and reported duration of fatigue were significantly associated with each of these domains. Persons with CFS reported high levels of healthcare utilization barriers for each domain: accessibility (34%), healthcare system (25%), and KABs (19%). In further examination of barrier domains to healthcare utilization, compared to non-fatigued persons adjusted ORs for CFS having “accessibility”, “KAB” and “Healthcare System” barrier domains decreased by 40%, 30%, and 19%, respectively.

CONCLUSION: Barriers to healthcare utilization pose a significant problem in persons with fatiguing illnesses. Study results suggested two-fold implications: a symptom-targeted model focusing on symptoms associated with fatigue; and an interactive model requiring efforts from patients and providers to improve interactions between them by reducing barriers in accessibility, KABs, and healthcare system.

 

Source: Lin JM, Brimmer DJ, Boneva RS, Jones JF, Reeves WC. Barriers to healthcare utilization in fatiguing illness: a population-based study in Georgia. BMC Health Serv Res. 2009 Jan 20;9:13. doi: 10.1186/1472-6963-9-13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651135/ (Full article)

 

Secondary structural changes of proteins in fingernails of chronic fatigue syndrome patients from Fourier-transform infrared spectra

Abstract:

BACKGROUND: Generally, nails can be an index of health, with abnormalities sometimes found under diseased conditions. Fatigue is also supposed to affect the condition of nails. Possible differences in infrared (IR) spectra of nail plates of chronic fatigue syndrome(CFS) patients compared to healthy control subjects were investigated in this study.

METHODS: Using an attenuated total reflection (ATR)-Fourier-transform infrared (FTIR) spectrophotometer, spectra in the region of 4000-600 cm(-1) were obtained. The amide I region was then separated by Fourier deconvolution and curve fitting based on the Gauss and Lorentz formula and revealed differences in the secondary structural content of proteins compared to healthy donors.

RESULTS: The specific secondary structural pattern commonly observed in nails of male and female CFS patients in the absence and presence of medication indicated a decreased alpha-helix content and increased beta-sheet content, suggesting reduced levels of normal elements of the nail plate.

CONCLUSIONS: This provides the first evidence of alterations in the fingernails of CFS patients which could be detected by IR spectroscopy. Possible explanations for the alterations will be discussed.

 

Source: Sakudo A, Kuratsune H, Kato YH, Ikuta K. Secondary structural changes of proteins in fingernails of chronic fatigue syndrome patients from Fourier-transform infrared spectra. Clin Chim Acta. 2009 Apr;402(1-2):75-8. doi: 10.1016/j.cca.2008.12.020. Epub 2008 Dec 30. https://www.ncbi.nlm.nih.gov/pubmed/19150612

 

Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants

Abstract:

BACKGROUND: This study attempted to longitudinally investigate neuropsychological function, illness representations, self-esteem, mood and quality of life (QoL) in individuals with chronic fatigue syndrome (CFS) and compared them with both healthy participants and a clinical comparison group of individuals with autoimmune thyroid disease (AITD).

METHOD: Neuropsychological evaluation was administered at two time points, five weeks apart. Twenty-one individuals with CFS, 20 individuals with AITD and 21 healthy participants were matched for age, pre-morbid intelligence, education level and socio-economic status (SES). All groups also completed measures of illness perceptions, mood, self-esteem and QoL at both time points.

RESULTS: The CFS group showed significantly greater impairment on measures of immediate and delayed memory, attention and visuo-constructional ability, and reported significantly higher levels of anxiety and depression. After controlling for the effects of mood, the CFS group still demonstrated significant impairment in attention. The CFS group also reported significantly lower self-reported QoL than the AITD and healthy participants. In terms of illness perceptions, the AITD group believed that their condition would last longer, that they had more treatment control over their condition, and reported less concern than the CFS group.

CONCLUSIONS: These results suggest that the primary cognitive impairment in CFS is attention and that this is not secondary to affective status. The lower treatment control perceptions and greater illness concerns that CFS patients report may be causally related to their affective status.

 

Source: Dickson A, Toft A, O’Carroll RE. Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants. Psychol Med. 2009 Sep;39(9):1567-76. doi: 10.1017/S0033291708004960. Epub 2009 Jan 15. https://www.ncbi.nlm.nih.gov/pubmed/19144216

 

Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms

Abstract:

PURPOSE OF REVIEW: The aim of this paper is to review recent findings on inflammatory and oxidative and nitrosative stress (IO&NS) pathways in chronic fatigue and somatization disorder.

RECENT FINDINGS: Activation of IO&NS pathways is the key phenomenon underpinning chronic fatigue syndrome (CFS): intracellular inflammation, with an increased production of nuclear factor kappa beta (NFkappabeta), cyclo-oxygenase-2 (COX-2) and inducible NO synthase (iNOS); and damage caused by O&NS to membrane fatty acids and functional proteins. These IO&NS pathways are induced by a number of trigger factors, for example psychological stress, strenuous exercise, viral infections and an increased translocation of LPS from gram-bacteria (leaky gut). The ‘psychosomatic’ symptoms experienced by CFS patients are caused by intracellular inflammation (aches and pain, muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection); damage caused by O&NS (aches and pain, muscular tension and fatigue); and gut-derived inflammation (complaints of irritable bowel). Inflammatory pathways (monocytic activation) are also detected in somatizing disorder.

SUMMARY: ‘Functional’ symptoms, as occurring in CFS and somatization, have a genuine organic cause, that is activation of peripheral and central IO&NS pathways and gut-derived inflammation. The development of new drugs, aimed at treating those disorders, should target these IO&NS pathways.

 

Source: Maes M. Inflammatory and oxidative and nitrosative stress pathways underpinning chronic fatigue, somatization and psychosomatic symptoms. Curr Opin Psychiatry. 2009 Jan;22(1):75-83. https://www.ncbi.nlm.nih.gov/pubmed/19127706

 

Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction

Abstract:

CONTEXT: Childhood trauma appears to be a potent risk factor for chronic fatigue syndrome (CFS). Evidence from developmental neuroscience suggests that early experience programs the development of regulatory systems that are implicated in the pathophysiology of CFS, including the hypothalamic-pituitary-adrenal axis. However, the contribution of childhood trauma to neuroendocrine dysfunction in CFS remains obscure.

OBJECTIVES: To replicate findings on the relationship between childhood trauma and risk for CFS and to evaluate the association between childhood trauma and neuroendocrine dysfunction in CFS.

DESIGN, SETTING, AND PARTICIPANTS: A case-control study of 113 persons with CFS and 124 well control subjects identified from a general population sample of 19 381 adult residents of Georgia.

MAIN OUTCOME MEASURES: Self-reported childhood trauma (sexual, physical, and emotional abuse; emotional and physical neglect), psychopathology (depression, anxiety, and posttraumatic stress disorder), and salivary cortisol response to awakening.

RESULTS: Individuals with CFS reported significantly higher levels of childhood trauma and psychopathological symptoms than control subjects. Exposure to childhood trauma was associated with a 6-fold increased risk of CFS. Sexual abuse, emotional abuse, and emotional neglect were most effective in discriminating CFS cases from controls. There was a graded relationship between exposure level and CFS risk. The risk of CFS conveyed by childhood trauma further increased with the presence of posttraumatic stress disorder symptoms. Only individuals with CFS and with childhood trauma exposure, but not individuals with CFS without exposure, exhibited decreased salivary cortisol concentrations after awakening compared with control subjects.

CONCLUSIONS: Our results confirm childhood trauma as an important risk factor of CFS. In addition, neuroendocrine dysfunction, a hallmark feature of CFS, appears to be associated with childhood trauma. This possibly reflects a biological correlate of vulnerability due to early developmental insults. Our findings are critical to inform pathophysiological research and to devise targets for the prevention of CFS.

 

Source: Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC. Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Arch Gen Psychiatry. 2009 Jan;66(1):72-80. doi: 10.1001/archgenpsychiatry.2008.508. https://www.ncbi.nlm.nih.gov/pubmed/19124690

 

Customizing treatment of chronic fatigue syndrome and fibromyalgia: the role of perpetuating factors

Erratum in: Psychosomatics. 2009 Mar-Apr;50(2):176.

Abstract:

BACKGROUND: Syndromes characterized by chronic, medically unexplained fatigue, effort- and stress-intolerance, and widespread pain are highly prevalent in medicine.

RESULTS: In chronic fatigue syndrome (CFS) and fibromyalgia (FM), various perpetuating factors may impair patients’ quality of life and functioning and impede recovery. Although cognitive-behavioral and graded-exercise therapy are evidence-based treatments, the effectiveness and acceptability of therapeutic interventions in CFS/FM may largely depend on a customized approach taking the heterogeneity of perpetuating factors into account.

CONCLUSION: Further research should clarify the aim and outcome of different treatment strategies in CFS/FM, as well as the underlying mechanisms of change, including those facilitating neurobiological recovery.

 

Source: Van Houdenhove B, Luyten P. Customizing treatment of chronic fatigue syndrome and fibromyalgia: the role of perpetuating factors. Psychosomatics. 2008 Nov-Dec;49(6):470-7. doi: 10.1176/appi.psy.49.6.470. https://www.ncbi.nlm.nih.gov/pubmed/19122123

 

Chronic fatigue syndrome and complement activation

Abstract:

This report describes a case of chronic fatigue syndrome (CFS) that followed a well-documented episode of acute Epstein-Barr virus (EBV) mononucleosis. All aetiological tests for chronic fatigue were found to be negative or normal, as were immunological tests. After 2 years of chronic fatigue following the acute illness, measurements of complement split products were performed to test for complement activation. These were positive and remained positive for 14 months, after which the patient then recovered from CFS.

 

Source: Geller RD, Giclas PC. Chronic fatigue syndrome and complement activation. BMJ Case Rep. 2009;2009. pii: bcr08.2008.0819. doi: 10.1136/bcr.08.2008.0819. Epub 2009 Mar 17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028106/ (Full article)

 

Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) is one of the more complex illnesses involving multiple systems within the body. Onset of ME/CFS frequently occurs quickly, and many patients report a prior exposure to a viral infection. This debilitating illness can affect the immune, neuroendocrine, autonomic, and neurologic systems.

Abnormal biological findings among some patients have included aberrant ion transport and ion channel activity, cortisol deficiency, sympathetic nervous system hyperactivity, EEG spike waves, left ventricular dysfunction in the heart, low natural killer cell cytotoxicity, and a shift from Th1 to Th2 cytokines. We propose that the kindling and oxidative stress theories provide a heuristic template for better understanding the at times conflicting findings regarding the etiology and pathophysiology of this illness.

 

Source: Jason LA, Porter N, Herrington J, Sorenson M, Kubow S. Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Behav Neurosci Res. 2009 Jan 1;7(2):1-17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022475/ (Full article)