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

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.     

Modafinil for Parkinson’s disease fatigue

Fatigue is common in Parkinson’s disease (PD), occurring in up to 42% of patients (2). There is no recognized treatment. This is a study of modafinil for Parkinson’s disease related fatigue. Ethical approval was given. Patients with idiopathic PD were recruited from a Movement Disorders clinic. Those with depression, dementia, and other causes for fatigue were excluded. Patients were assessed using the Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), self-rating of improvement, Epworth Sleepiness Scale (ESS), and UPDRS. Modafinil was titrated up over 4 weeks to maximum of 400 mg/day. There followed a 5 week maintenance phase before reassessment. Thirteen patients participated. No significant change was seen in any safety measure. The FSS did not change significantly, however those on modafinil rated an improvement in their fatigue compared to placebo. The Modafinil group had a statistically significant improvement on ESS (p < 0.05). This is a small study of modafinil in selected PD patients. There is a suggestion of improvement on the global clinical impression scale for fatigue, but no significant change on FSS. A larger study is needed to further evaluate this drug in PD fatigue. This study highlights the problems with recruitment when trialing treatments of non-motor symptoms in PD. A significant improvement in EDS was seen.     

Does motoneuron adaptation contribute to muscle fatigue?

To help reduce the gap between the cellular physiology of motoneurons (MNs) as studied "bottom-up" in animal preparations and the "top-down" study of the firing patterns of human motor units (MUs), this article addresses the question of whether motoneuron adaptation contributes to muscle fatigue. Findings are reviewed on the intracellularly recorded electrophysiology of spinal MNs as studied in vivo and in vitro using animal preparations, and the extracellularly recorded discharge of MUs as studied in conscious humans. The latter "top-down" approach, combined with kinetic measurements, has provided most of what is currently known about the neurobiology of muscle fatigue, including its task and context dependencies. It is argued that although the question addressed is still open, it should now be possible to design new "bottom-up" research paradigms using animal preparations that take advantage of what has been learned with the use of relatively noninvasive quantitative procedures in conscious humans.     

Factor analysis of symptoms among subjects with unexplained chronic fatigue: what can we learn about chronic fatigue syndrome?

OBJECTIVE: Chronic fatigue syndrome (CFS) case definitions agree that fatigue must be unexplained, debilitating and present for at least 6 months, but they differ over accompanying symptoms. Our objective was to compare the 1994 CFS case-defining symptoms with those identified by factor analysis. METHODS: We surveyed the Wichita population and measured the occurrence of 21 symptoms in 1391 chronically fatigued subjects who did not report fatigue-associated medical or psychiatric conditions. We used factor analyses to identify symptom dimensions of fatigue and cluster analysis to assign subjects to subgroups. RESULTS: Forty-three subjects had CFS. We confirmed three factors: musculoskeletal, infection and cognition-mood-sleep, essentially defined by CFS symptoms. Although factor scores were higher among CFS subjects, CFS and non-CFS distributions overlapped substantially. Three clusters also showed overlap between CFS and non-CFS subjects. CONCLUSION: CFS symptomatology is a multidimensional phenomenon overlapping with other unexplained fatiguing syndromes and this must be considered in CFS research.     

Predicting fatigue 1 year after aneurysmal subarachnoid hemorrhage

Fatigue is an important contributor to quality of life in patients who survive aneurysmal subarachnoid hemorrhage (SAH), but the determinants of this fatigue are unclear. We assessed the occurrence of fatigue 1 year after SAH and its relation to physical or cognitive impairment, passive coping, and emotional problems, measured 3 months after SAH. This was a prospective cohort study of 108 patients who visited our SAH outpatient clinic 3 months after SAH and who were living independently in the community 1 year after SAH. Fatigue was evaluated using the Fatigue Severity Scale (FSS). Analysis of variance was used to analyze the data. Fatigue (FSS ≥4) was present in 77 patients (71%). Mean FSS scores were 4.1 (SD 1.6) in the group of patients having ‘neither physical nor cognitive impairment,’ 5.2 (1.4) having ‘either physical or cognitive impairment,’ and 5.9 (0.9) having ‘both physical and cognitive impairments.’ Mean FSS scores were higher in patients scoring high on passive coping (85 vs. 58%; RR 1.46, 95% CI 1.13–1.87), anxiety (84 vs. 55%; RR 1.53, 95% CI 1.17–2.02), or depression (85 vs. 62%; RR 1.36, 95% CI 1.08–1.72) than in patients without these complaints. Relationships between these complaints and FSS scores were higher in patients having neither physical nor cognitive impairments than in patients having physical or cognitive impairments. Fatigue is common after SAH and is related to physical and cognitive impairments. In patients with neither physical nor cognitive impairments, passive coping style and emotional problems are important predictors of fatigue.     

Does a decrease in avoidance behavior and focusing on fatigue mediate the effect of cognitive behavior therapy for chronic fatigue syndrome?

Objective

Cognitive behavior therapy (CBT) leads to a significant reduction in fatigue severity and impairment in patients with chronic fatigue syndrome (CFS). The purpose of the present study was to determine whether the effect of CBT for CFS on fatigue and impairment is mediated by a decrease in avoidance behavior and focusing on fatigue.

Methods

For this purpose, we reanalyzed a randomized controlled trial which was previously conducted to test the efficacy of CBT for CFS. Two hundred nineteen patients completed assessment prior and subsequent to treatment or a control group period.

Results

Mediation analysis revealed that a decrease in focusing on fatigue mediated the effect of CBT for CFS on fatigue and impairment. Avoidance of activity and avoidance of aversive stimuli were not significantly changed by treatment and were therefore excluded from mediation analysis.

Conclusion

A decrease in the focus on fatigue seems to contribute to the treatment effect of CBT for CFS.     

Exacting assessments: do older adults fatigue more quickly?

To determine whether neuropsychological testing is fatiguing, and whether it is more fatiguing to older than younger adults, 351 healthy, community living adults, between 18 and 91 years of age, completed a 3 to 4 hour battery of tests focusing on sensation, perception, attention, memory and knowledge. The battery included 3 critical tests: one for assessing the speed of making simple reactions and two for assessing the speed of making decisions. For half of the participants, the critical tests were administered only once, at the end of the session; for the remaining participants, the critical tests were given at the beginning and end of the session. The results show no evidence of fatigue effects with participants from any age group. In view of the type and variety of instruments in our battery, we believe our results will generalize to a wide range of testing situations. The participants in our study were healthy adult volunteers, however, and thus we recommend caution in generalizing the results to clinical populations.     

Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinson's disease?

Patients with Parkinson's disease often complain of fatigue, and although cardiac sympathetic denervation is thought to be associated with fatigue, this link remains unclear. Previously, we detected cardiac sympathetic denervation in patients with Parkinson's disease using dobutamine, a selective beta‐1 stimulant. To clarify the involvement of autonomic dysfunction in fatigue in Parkinson's disease, we conducted autonomic function tests on 33 patients with Parkinson's disease (mean age, 66.1 ± 5.6 years; 20 men, 13 women) and evaluated their relationships to fatigue. We divided patients into 2 groups, fatigued (n = 12) and nonfatigued (n = 21), based on an average score ≥ 3.3 on the Parkinson fatigue scale. Autonomic function tests included the coefficient of variation of R–R intervals, head‐up tilt test, norepinephrine and dobutamine infusion tests, and cardiac ¹²³I‐metaiodobenzylguanidine scintigraphy. The coefficient of variation of R–R intervals and the systolic blood pressure changes accompanying the head‐up tilt test did not show significant differences between the 2 groups; however, the pressor responses in the norepinephrine and dobutamine infusion tests were significantly greater in the fatigued group than in the nonfatigued group. The ¹²³I‐metaiodobenzylguanidine heart‐to‐mediastinal uptake ratio was lower in the fatigued group than in the nonfatigued group. Partial correlation analyses, using disease duration and Hoehn and Yahr stage as control variables, also demonstrated significant correlations between the Parkinson fatigue scale score and the results of the autonomic function tests and cardiac ¹²³I‐metaiodobenzylguanidine uptake. Our results suggest that autonomic dysfunction, including cardiac sympathetic denervation, is associated with fatigue in patients with Parkinson's disease. © 2011 Movement Disorder Society     

The process of cognitive behaviour therapy for chronic fatigue syndrome: Which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue?

Objective

Cognitive behaviour therapy (CBT) can significantly reduce fatigue in chronic fatigue syndrome (CFS), but little is known about the process of change taking place during CBT. Based on a recent treatment model (Wiborg et al. J Psych Res 2012), we examined how (changes in) cognitions and behaviour are related to the decrease in fatigue.

Methods

We included 183 patients meeting the US Centers for Disease Control criteria for CFS, aged 18 to 65 years, starting CBT. We measured fatigue and possible process variables before treatment; after 6, 12 and 18 weeks; and after treatment. Possible process variables were sense of control over fatigue, focusing on symptoms, self-reported physical functioning, perceived physical activity and objective (actigraphic) physical activity. We built multiple regression models, explaining levels of fatigue during therapy by (changes in) proposed process variables.

Results

We observed large individual variation in the patterns of change in fatigue and process variables during CBT for CFS. Increases in the sense of control over fatigue, perceived activity and self-reported physical functioning, and decreases in focusing on symptoms explained 20 to 46% of the variance in fatigue. An increase in objective activity was not a process variable.

Conclusion

A change in cognitive factors seems to be related to the decrease in fatigue during CBT for CFS. The pattern of change varies considerably between patients, but changes in process variables and fatigue occur mostly in the same period.     

Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?

Journal of NeuroVirology - SARS-CoV-2 survivors may report persistent symptoms that resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We explored (a) ME/CFS-like symptom...     

Nerve conduction studies in relation to residual fatigue in Guillain-Barré syndrome

Many Guillain-Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients recover well, but suffer from excessive fatigue, which may persist for years and reduce the quality of life considerably. In order to determine whether residual subclinical peripheral nerve dysfunction is a possible underlying mechanism of fatigue, we performed standardized nerve conduction (NC) studies in 16 fatigued patients, mean 6.5 years after diagnosis. Thirteen were relatively well recovered from GBS and 3 had stable CIDP. In contrast to CIDP, most NC values in GBS patients were remarkably restored and within normal values.No correlations were found between the electrophysiological findings and the fatigue scores,muscle strength, or functional scores. This study demonstrates that fatigue in GBS is not explained by residual nerve dysfunction, using conventional NC measurements.     

What is chronic fatigue syndrome? Heterogeneity within an international multicentre study

OBJECTIVE: We sought to compare the characteristics of patients presenting with chronic fatigue (CF) and related syndromes in eight international centres and to subclassify these subjects based on symptom profiles. The validity of the subclasses was then tested against clinical data. METHOD: Subjects with a clinical diagnosis of CF completed a 119-item self-report questionnaire to provide clinical symptom data and other information such as illness course and functional impairment. Subclasses were generated using a principal components-like analysis followed by latent profile analysis (LPA). RESULTS: 744 subjects returned complete data sets (mean age 40.8 years, mean length of illness 7.9 years, female to male ratio 3:1). Overall, the subjects had a high rate of reporting typical CF symptoms (fatigue, neuropsychological dysfunction, sleep disturbance). Using LPA, two subclasses were generated. Class one (68% sample) was characterized by: younger age, lower female to male ratio; shorter episode duration; less premorbid, current and familial psychiatric morbidity; and, less functional disability. Class two subjects (32%) had features more consistent with a somatoform illness. There was substantial variation in subclass prevalences between the study centres (Class two range 6-48%). CONCLUSIONS: Criteria-based approaches to the diagnosis of CF and related syndromes do not select a homogeneous patient group. While substratification of patients is essential for further aetiological and treatment research, the basis for allocating such subcategories remains controversial.     

Chronic fatigue syndrome or affective disorder? Implications of the diagnosis on management

This paper reports a case of a 13 1/2 year old boy with a bipolar affective disorder, who was assumed to be suffering from a post-viral fatigue syndrome. The diagnostic problems in differenting the postviral fatigue syndrome from affective disorders in children/adolescents are discussed. The consequences of misdiagnosis in young people, bearing in mind the developmental tasks that they face, are considered.

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Zusammenfassung Es wird ein 13 1/2 Jahre alter Junge mit einer bipolaren, manisch-depressiven Krankheit beschrieben, die kurz nach viralen Symptomen begann und deswegen als postvirales Ermüdungssyndrom betrachtet wurde. Die differential-diagnostischen Schwierigkeiten der Unterscheidung zwischen affektiven Krankheiten und postviralem Ermüdungssyndrom im Jugendalter werden beleuchtet. Die Konsequenzen einer falschen Diagnose bei Jugendlichen angesichts der Entwicklungsaufgaben dieses Alters werden erörtert.

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Résumé Cet article décrit le cas d'un garcon, âgé 13 1/2 ans avec un trouble affectif bipolaire. Sa maladie, précédée par une épisode de symptômes viraux, était diagnostiquée erronément comme syndrôme de fatigue post-viral. Les problèmes du diagnostic-differentiel de la distinction entre syndrômes de fatigues et maladies affectives dans la jeunesse/ad-olescence, sont mis au lumière. Les conséquences d'un faux diagnostic dans la jeunesse, peuvent être graves, tenant compte des tâches développementales de cet âge.

     

Contribution of central and peripheral factors to residual fatigue in Guillain-Barré syndrome

Many patients with Guillain-Barré syndrome (GBS) suffer from severe residual fatigue that has an uncertain basis. We determined the relative contribution of peripheral and central factors during a 2-min fatiguing sustained maximal voluntary contraction (MVC) in 10 neurologically well-recovered GBS patients and 12 age- and sex-matched healthy controls. Physiological fatigue was defined as the decline of voluntary force during an MVC of the biceps brachii. Relative amounts of peripheral fatigue and central activation failure were determined combining voluntary force and force responses to electrical stimulation. Surface electromyography was used to determine muscle-fiber conduction velocity. During the first minute of sustained MVC, peripheral fatigue developed more slowly in patients than in controls. Central fatigue only occurred in patients. The muscle-fiber conduction velocity was higher in patients. The initial MVC, decrease of MVC, initial force response, and initial central activation failure did not significantly differ between the groups. Although peripheral mechanisms cannot be excluded in the pathogenesis of residual fatigue after GBS, these results suggest that central changes are involved. This study thus provides further insight into the factors contributing to residual fatigue in GBS patients.     

The brain at work: a cerebral metabolic manifestation of central fatigue?

Central fatigue refers to circumstances in which strength appears to be limited by the ability of the central nervous system to recruit motoneurons. Central fatigue manifests when the effort to contract skeletal muscles is intense and, thus, is aggravated when exercise is performed under stress, whereas it becomes attenuated following training. Central fatigue has not been explained, but the cerebral metabolic response to intense exercise, as to other modalities of cerebral activation, is a reduction in its "metabolic ratio" (MR), i.e., the brain's uptake of oxygen relative to that of carbohydrate. At rest the MR is close to 6 but during intense whole-body exercise it decreases to less than 3, with the uptake of lactate becoming as important as that of glucose. It remains debated what underlies this apparent inability of the brain to oxidize the carbohydrate taken up, but it may approach approximately 10 mmol glucose equivalents. In the case of exercise, a concomitant uptake of ammonium for formation of amino acids may account for only approximately 10% of this "extra" carbohydrate taken up. Also, accumulation of intermediates in metabolic pathways and compartmentalization of metabolism between astrocytes and neurons are avenues that have to be explored. Depletion of glycogen stores and subsequent supercompensation during periods of low neuronal activity may not only play a role but also link brain metabolism to its function.