Glucocorticoid receptor mediated negative feedback in chronic fatigue syndrome using the low dose (0.5 mg) dexamethasone suppression test

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is associated with hypocortisolism, but it is not yet clear the extent to which enhanced negative feedback may underlie this finding.

METHODS: We undertook a low-dose dexamethasone (0.5 mg) suppression test in 18 CFS patients and 20 matched, healthy controls. We measured salivary cortisol levels at 0800 h, 1200 h, 1600 h and 2000 h before and after the administration of 0.5 mg of dexamethasone.

RESULTS: Basal cortisol output was raised in this group of CFS patients compared to controls. Overall, the percentage suppression following dexamethasone administration was no different between CFS (mean+/-sem: 80.4+/-4.4%) and controls (76.2+/-4.9 %). However, the sub-group of patients with CFS and comorbid depression (n=9) showed a significant hypersuppression of salivary cortisol in response to dexamethasone (89.0+/-1.9%; p<0.05 v controls).

LIMITATIONS: The sub-group analysis was on small numbers and should be considered preliminary. Dexamethasone probes only glucocorticoid medicated negative feedback but does not probe mineralocorticoid feedback, the other main physiological feedback mechanism.

CONCLUSION: We found partial support for the hypothesis of enhanced negative feedback in CFS but only in patients with comorbid depression and also in the context of a sample of patients with elevated basal cortisol levels, which is an atypical finding in the literature.

 

Source: Papadopoulos A, Ebrecht M, Roberts AD, Poon L, Rohleder N, Cleare AJ. Glucocorticoid receptor mediated negative feedback in chronic fatigue syndrome using the low dose (0.5 mg) dexamethasone suppression test. J Affect Disord. 2009 Jan;112(1-3):289-94. doi: 10.1016/j.jad.2008.05.001. Epub 2008 Jun 24. https://www.ncbi.nlm.nih.gov/pubmed/18573538

 

Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are poorly understood disorders that share similar demographic and clinical characteristics. The etiology and pathophysiology of these diseases remain unclear. Because of the similarities between both disorders it was suggested that they share a common pathophysiological mechanisms, namely, central nervous system (CNS) dysfunction. Current hypotheses center on atypical sensory processing in the CNS and dysfunction of skeletal muscle nociception and the hypothalamic-pituitary-adrenal (HPA) axis.

Researches suggest that the (CNS) is primarily involved in both disorders in regard to the pain, fatigue and sleep disturbances. Many patients experience difficulty with concentration and memory and many others have mood disturbance, including depression and anxiety. Although fibromyalgia is common and associated with substantial morbidity and disability, there are no US Food and Drug Administration (FDA)-approved treatments except pregabalin.

Recent pharmacological treatment studies about fibromyalgia have focused on selective serotonin and norepinephrine (NE) reuptake inhibitors, which enhance serotonin and NE neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications. CFS is a descriptive term used to define a recognisable pattern of symptoms that cannot be attributed to any alternative condition. The symptoms are currently believed to be the result of disturbed brain function.

To date, no pharmacological agent has been reliably shown to be effective treatment for CFS. Management strategies are therefore primarily directed at relief of symptoms and minimising impediments to recovery. This chapter presents data demonstrating CFS, abnormal pain processing and autonomic nervous system (ANS) dysfunction in FM and CFS and concludes by reviewing the new concepts in treatments in CFS and FM.

 

Source: Gur A, Oktayoglu P. Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment. Curr Pharm Des. 2008;14(13):1274-94. https://www.ncbi.nlm.nih.gov/pubmed/18537652

 

Gait characteristics of subjects with chronic fatigue syndrome and controls at self-selected and matched velocities

Abstract:

BACKGROUND: Gait abnormalities have been reported in individuals with Chronic Fatigue Syndrome (CFS) however no studies exist to date investigating the kinematics of individuals with CFS in over-ground gait. The aim of this study was to compare the over-ground gait pattern (sagittal kinematics and temporal and spatial) of individuals with CFS and control subjects at their self-selected and at matched velocities.

METHODS: Twelve individuals with CFS and 12 matched controls participated in the study. Each subject walked along a 7.2 m walkway three times at each of three velocities: self-selected, relatively slow (0.45 ms-1) and a relatively fast (1.34 ms-1). A motion analysis system was used to investigate the sagittal plane joint kinematics and temporal spatial parameters of gait.

RESULTS: At self-selected velocity there were significant differences between the two groups for all the temporal and spatial parameters measured, including gait velocity (P = 0.002). For the kinematic variables the significant differences were related to both ankles during swing and the right ankle during stance. At the relatively slower velocity the kinematic differences were replicated. However, the step distances decreased in the CFS population for the temporal and spatial parameters. When the gait pattern of the individuals with CFS at the relatively fast walking velocity (1.30 +/- 0.24 ms-1) was compared to the control subjects at their self-selected velocity (1.32 +/- 0.15 ms-1) the gait pattern of the two groups was very similar, with the exception of both ankles during swing.

CONCLUSION: The self-selected gait velocity and/or pattern of individuals with CFS may be used to monitor the disease process or evaluate therapeutic intervention. These differences may be a reflection of the relatively low self-selected gait velocity of individuals with CFS rather than a manifestation of the condition itself.

 

Source: Paul L, Rafferty D, Wood L, Maclaren W. Gait characteristics of subjects with chronic fatigue syndrome and controls at self-selected and matched velocities. J Neuroeng Rehabil. 2008 May 27;5:16. doi: 10.1186/1743-0003-5-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424058/ (Full article)

 

Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate

Abstract:

Chronic fatigue syndrome (CFS) is a distinct entity belonging to the group of persistent fatigue that can be challenging to diagnose and to treat. It is characterized by a combination of prolonged fatigue, other nonspecific somatic manifestations and neuropsychological symptoms, including difficulties with concentration, short-term memory and thinking, as well as impaired attention and slowed processing speed. Neurostimulants increasing dopamine and norepinephrine activity, such as bupropion, dextroamphetamine and recently immediate-release methylphenidate have been advocated to improve neurocognitive deficits. The use of immediate-release methylphenidate in CFS has been shown in one small study. Using the positive results of this study and the well-known beneficial effects of the drug on a range of similar cognitive symptoms in attention-deficit/hyperactivity disorder, this perspective addresses CFS and other related disorders and provides a discussion on the potential promising role of methylphenidate in the therapeutic armamentarium of CFS.

 

Source: Valdizán Usón JR, Idiazábal Alecha MA. Diagnostic and treatment challenges of chronic fatigue syndrome: role of immediate-release methylphenidate. Expert Rev Neurother. 2008 Jun;8(6):917-27. Doi: 10.1586/14737175.8.6.917. https://www.ncbi.nlm.nih.gov/pubmed/18505357

 

‘Physical or psychological?’- a comparative study of causal attribution for chronic fatigue in Brazilian and British primary care patients

Abstract:

OBJECTIVE: Causal attribution influences symptom experience, help-seeking behaviour and prognosis in chronic fatigue syndrome. We compared causal attribution of patients with unexplained chronic fatigue (UCF) in Brazil and Britain.

METHOD: Primary care attenders in São Paulo (n = 3914) and London (n = 2459) were screened for the presence of UCF. Those with UCF (São Paulo n = 452; London n = 178) were assessed for causal attribution (physical vs. psychosocial), perceived chronicity (i.e. reported duration of fatigue) and disability.

RESULTS: British UCF patients were more likely to attribute their fatigue to physical causes (adjusted odds ratio 1.70, P = 0.037) and perceived their fatigue to be more chronic (adjusted beta 0.15, P = 0.002). There was no significant difference in current disability (adjusted beta -0.01, P = 0.81).

CONCLUSION: Despite similar disability levels, UCF patients in different cultural settings presented different attributions and perceptions about their illness. Sociocultural factors may have an important role in shaping illness attribution and perception around chronic fatigue.

 

Source: Cho HJ, Bhugra D, Wessely S. ‘Physical or psychological?’- a comparative study of causal attribution for chronic fatigue in Brazilian and British primary care patients. Acta Psychiatr Scand. 2008 Jul;118(1):34-41. doi: 10.1111/j.1600-0447.2008.01200.x. Epub 2008 May 22. https://www.ncbi.nlm.nih.gov/pubmed/18498433

 

Obstructions for quality care experienced by patients with chronic fatigue syndrome (CFS)–a case study

Abstract:

OBJECTIVE: To explore obstructions for quality care from experiences by patients suffering from chronic fatigue syndrome (CFS).

METHODS: Qualitative case study with data drawn from a group meeting, written answers to a questionnaire and a follow-up meeting. Purposeful sample of 10 women and 2 men of various ages, recruited from a local patient organization, assumed to have a special awareness for quality care.

RESULTS: CFS patients said that lack of acknowledgement could be even worse than the symptoms. They wanted their doctors to ask questions, listen to them and take them seriously, instead of behaving degrading. Many participants felt that the doctors psychologized too much, or trivialized the symptoms. Participants described how doctors’ lack of knowledge about the condition would lead to long-term uncertainty or maltreatment. Even with doctors who were supportive, it would usually take months and sometimes years until a medical conclusion would be reached, or other disorders were ruled out. Increased physical activity had been recommend, but most of the informants experienced that this made them worse.

CONCLUSION: Current medical scepticism and ignorance regarding CFS shapes the context of medical care and the illness experiences of CFS patients, who may feel they neither get a proper assessment nor management.

PRACTICE IMPLICATIONS: CFS patients’ reports about patronizing attitudes and ignorance among doctors call for development of evidence based strategies and empowerment of patients, acknowledging the patients’ understanding of symptoms and the complex nature of the disease. The NICE guidelines emphasize the need of patient participation and shared decision-making.

Comment in: Qualitative methods in communication and patient education research. [Patient Educ Couns. 2008]

 

Source: Gilje AM, Söderlund A, Malterud K. Obstructions for quality care experienced by patients with chronic fatigue syndrome (CFS)–a case study. Patient Educ Couns. 2008 Oct;73(1):36-41. doi: 10.1016/j.pec.2008.04.001. Epub 2008 May 16. https://www.ncbi.nlm.nih.gov/pubmed/18486415

 

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia

Abstract:

INTRODUCTION: We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal.

METHODS: We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase.

RESULTS: CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night’s sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group.

CONCLUSION: CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before. This sleep disruption may explain the overwhelming fatigue, report of unrefreshing sleep, and pain in this subgroup of patients.

Comment in: How much sleep apnea is too much? [Arthritis Res Ther. 2009]

 

Source: Togo F, Natelson BH, Cherniack NS, FitzGibbons J, Garcon C, Rapoport DM. Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia. Arthritis Res Ther. 2008;10(3):R56. doi: 10.1186/ar2425. Epub 2008 May 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483445/ (Full article)

 

Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diagnosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of >or=2.5. Genes showing differential expression were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymerase chain reaction.

Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downregulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

 

Source: Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey DL, Richards SC, Montgomery J, Baldwin DA, Kellam P, Harrison TJ, Griffin GE, Main J,Enlander D, Nutt DJ, Holgate ST. Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis. 2008 Apr 15;197(8):1171-84. doi: 10.1086/533453.  http://jid.oxfordjournals.org/content/197/8/1171.long (Full article)

 

A systematic review of chronic fatigue syndrome: don’t assume it’s depression

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) is characterized by profound, debilitating fatigue and a combination of several other symptoms resulting in substantial reduction in occupational, personal, social, and educational status. CFS is often misdiagnosed as depression. The objective of this study was to evaluate and discuss different etiologies, approaches, and management strategies of CFS and to present ways to differentiate it from the fatigue symptom of depression.

DATA SOURCES: A MEDLINE search was conducted to identify existing information about CFS and depression using the headings chronic fatigue syndrome AND depression. The alternative terms major depressive disorder and mood disorder were also searched in conjunction with the term chronic fatigue syndrome. Additionally, MEDLINE was searched using the term chronic fatigue. All searches were limited to articles published within the last 10 years, in English. A total of 302 articles were identified by these searches. Also, the term chronic fatigue syndrome was searched by itself. This search was limited to articles published within the last 5 years, in English, and resulted in an additional 460 articles. Additional publications were identified by manually searching the reference lists of the articles from both searches.

STUDY SELECTION AND DATA EXTRACTION: CFS definitions, etiologies, differential diagnoses (especially depression) and management strategies were extracted, reviewed, and summarized to meet the objectives of this article.

DATA SYNTHESIS: CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression. Genetic, immunologic, infectious, metabolic, and neurologic etiologies were suggested to explain CFS. A biopsychosocial model was suggested for evaluating, managing, and differentiating CFS from depression.

CONCLUSIONS: Evaluating and managing chronic fatigue is a challenging situation for physicians, as it is a challenging and difficult condition for patients. A biopsychosocial approach in the evaluation and management is recommended. More studies about CFS manifestations, evaluation, and management are needed.

 

Source: Griffith JP, Zarrouf FA. A systematic review of chronic fatigue syndrome: don’t assume it’s depression. Prim Care Companion J Clin Psychiatry. 2008;10(2):120-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292451/ (Full article)

 

Comorbid somatic symptoms and functional status in patients with fibromyalgia and chronic fatigue syndrome: sensory amplification as a common mechanism

Abstract:

BACKGROUND: Somatic symptoms are common in conditions such as fibromyalgia (FM) and chronic fatigue syndrome (CFS).

OBJECTIVE: Authors investigated a potential shared pathologic mechanism: a generalized perceptual abnormality where there is heightened responsiveness to varied sensory stimulation, including pain.

METHOD: A composite measure of sensory sensitivity was created and compared with measures of somatic symptoms, comorbid psychological disturbances, and self-reported physical functioning in 38 patients with FM and/or CFS.

RESULTS: Sensory amplification influenced physical functioning indirectly through pain intensity, and physical symptoms and fatigue also independently contributed to physical functioning.

CONCLUSION: Sensory amplification may be an underlying pathophysiologic mechanism in these disorders that is relatively independent of depression and depressive symptoms.

 

Source: Geisser ME, Strader Donnell C, Petzke F, Gracely RH, Clauw DJ, Williams DA. Comorbid somatic symptoms and functional status in patients with fibromyalgia and chronic fatigue syndrome: sensory amplification as a common mechanism. Psychosomatics. 2008 May-Jun;49(3):235-42. doi: 10.1176/appi.psy.49.3.235. https://www.ncbi.nlm.nih.gov/pubmed/18448779