The neuropsychiatry of chronic fatigue syndrome

Abstract:

This paper explores the relationship between chronic fatigue syndrome (CFS) and psychiatric disorder, with special reference to neuropsychiatry, Topics reviewed include (1) epidemiological evidence of central disorder in CFS; (2) evidence from longitudinal studies of an interaction between vulnerability to CFS and psychiatric disorder; and (3) evidence from neuroimaging, neuropsychology, neurophysiology and neuroendocrinology of disordered CNS function in CFS. The most impressive evidence of CNS disturbance comes from neuroendocrinological studies, which suggest a role of hypothalamic disorder as a final common pathway for CFS. It is concluded that the equal and opposite tendencies of psychiatry to be ‘brainless’ and neurology to be ‘mindless’ have led to needless controversy over the nature of CFS. Now that the contributions of psychiatric disorder to CFS, and of neurobiological dysfunction to psychiatric disorder, are both established, it will be possible to make real advances in understanding the nature of CFS.

 

Source: Wessely S. The neuropsychiatry of chronic fatigue syndrome. Ciba Found Symp. 1993;173:212-29; discussion 229-37. http://www.ncbi.nlm.nih.gov/pubmed/8491099

 

Immunity and the pathophysiology of chronic fatigue syndrome

Abstract:

The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge.

Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity. Cutaneous anergy and immunoglobulin G subclass deficiencies have also been found.

Further studies are needed examining cytokine levels in serum and cerebrospinal fluid, and cytokine production in vitro in patients with CFS. Interpretation of the findings of published studies of immunity is limited by probable heterogeneity in the patient groups studied, and by the lack of standardization and reproducibility in the assays used.

The pattern of abnormalities reported in immunological testing in patients with CFS is consistent with the changes seen during the resolving phases of acute viral infection. These data provide circumstantial support for the hypothesis that CFS results from a disordered immune response to an infection. Longitudinal studies of immunity in patients developing CFS after defined infectious illnesses will provide the best means of further examining this hypothesis.

 

Source: Lloyd AR, Wakefield D, Hickie I. Immunity and the pathophysiology of chronic fatigue syndrome. Ciba Found Symp. 1993;173:176-87; discussion 187-92. http://www.ncbi.nlm.nih.gov/pubmed/8491097

 

Muscle histopathology and physiology in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue at rest which is made worse by exercise. Previous biopsy studies on small numbers of CFS patients have shown a range of morphological changes to which have been attributed fatigue and myalgia.

We have now studied 108 patients with CFS or muscle pain and 22 normal volunteers by light and electron microscopy. There was no consistent correlation between symptoms and changes in fibre type prevalence, fibre size, degenerative or regenerative features, glycogen depletion, or mitochondrial abnormalities. Physiological contractile properties of quadriceps (maximal isometric force generation, frequency: force characteristics and relaxation rate) were also examined before and for up to 48 hours after a symptom-limited incremental cycle ergometer exercise test in 12 CFS patients and 12 normal volunteers.

Voluntary and stimulated force characteristics were normal at rest and during recovery. Exercise duration was similar in the two groups although CFS patients had higher perceived exertion scores in relation to heart rate during exercise, indicating a reduced effort sensation threshold. On physiological and pathological grounds it is clear that CFS is not a myopathy. Psychological/psychiatric factors appear to be of greater importance in this condition.

 

Source: Edwards RH1, Gibson H, Clague JE, Helliwell T. Muscle histopathology and physiology in chronic fatigue syndrome. Ciba Found Symp. 1993;173:102-17; discussion 117-31. http://www.ncbi.nlm.nih.gov/pubmed/8491096

 

Hypothesis: the nasal fatigue reflex

Abstract:

Natural selection results in adaptations. I suggest that unexplained fatigue may be an adaptive response to nasal impairment.

For macrosmatic animals, intact olfaction is necessary to detect predators. In such animals, any reflex (e.g., fatigue) triggered by nasal dysfunction that limited exposure would offer great survival advantage. The “fatigued” animal would remain in its protected environment, unexposed to hungry carnivores, while the nose healed.

In humans, clinical syndromes associated with unexplained fatigue (chronic fatigue syndrome, tension fatigue syndrome, allergic fatigue, neurasthenia, etc.) are characterized by symptoms that, in part, are nasal in origin.

The older medical literature does describe the resolution of fatigue in neurasthenia after nasal treatments. Nasal reflexes in animals do cause significant systemic effects, including an inhibition of muscle action potentials that is, perhaps, analogous to the “heavy-limbed” sensation of those with fatigue.

Furthermore, reflexes similar to the one proposed do exist in humans: the diving reflex presumably served our amphibian ancestors well as an oxygen conserving technique with submersion, but serves no known useful function now. Other human nasopharyngeal reflexes with profound cardiovascular and systemic effects are well described but only occasionally studied. The proposed nasal fatigue reflex should be examined as a possible ancient adaptive response to nasal malfunction.

 

Source: Chester AC. Hypothesis: the nasal fatigue reflex. Integr Physiol Behav Sci. 1993 Jan-Mar;28(1):76-83. http://www.ncbi.nlm.nih.gov/pubmed/8476744

 

Development of a fatigue scale

Abstract:

A self-rating scale was developed to measure the severity of fatigue. Two-hundred and seventy-four new registrations on a general practice list completed a 14-item fatigue scale. In addition, 100 consecutive attenders to a general practice completed the fatigue scale and the fatigue item of the revised Clinical Interview Schedule (CIS-R). These were compared by the application of Relative Operating Characteristic (ROC) analysis. Tests of internal consistency and principal components analyses were performed on both sets of data. The scale was found to be both reliable and valid. There was a high degree of internal consistency, and the principal components analysis supported the notion of a two-factor solution (physical and mental fatigue). The validation coefficients for the fatigue scale, using an arbitrary cut off score of 3/4 and the item on the CIS-R were: sensitivity 75.5 and specificity 74.5.

 

Source: Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147-53. http://www.ncbi.nlm.nih.gov/pubmed/8463991

 

Chronic fatigue syndrome: influence of histamine, hormones and electrolytes

Abstract:

The chronic fatigue syndrome is poorly understood. We believe the underlying causes in many atopics and women are a persistent infection and hypersensitivity to the immune-suppressive effects of histamine and certain pathogens.

We believe much of the symptomatology can be explained by all four types of hypersensitivity (Gell and Coombs classification) in reaction to a pathogen, electrolyte disturbances which include sometimes permanent changes in cell membranes’ ability to pass electrolytes, sometimes permanent biochemical changes in mitochondrial function, and disturbances of insulin and T3-thyroid hormone functions. We also explain in detail what ‘fatigue’ means for these patients. We present evidence from the medical literature for the plausibility of our hypotheses.

 

Source: Dechene L. Chronic fatigue syndrome: influence of histamine, hormones and electrolytes. Med Hypotheses. 1993 Jan;40(1):55-60. http://www.ncbi.nlm.nih.gov/pubmed/8455468

 

A four-year follow-up study in fibromyalgia. Relationship to chronic fatigue syndrome

Abstract:

The primary objectives of this study were to examine to what extent fibromyalgia patients later on developed presumpted causative somatic diseases and to examine symptoms and muscle strength some years after the diagnosis of fibromyalgia was established. A secondary objective was to describe the overlap between fibromyalgia and chronic fatigue syndrome.

Only in two of 91 the muscle pain was found to be caused by another somatic disease during the median 4 year follow-up period. In one of the 83 attending subjects a somatic disease associated with muscle symptoms was established at the follow-up visit. 60 out of 83 reported increased pain, 8 reported improvement of pain. The 83 subjects showed no significant fall in muscle strength during the follow-up period. The majority reported severe fatigue but only one fifth fulfilled the proposed chronic fatigue syndrome criteria.

 

Source: Nørregaard J, Bülow PM, Prescott E, Jacobsen S, Danneskiold-Samsøe B. A four-year follow-up study in fibromyalgia. Relationship to chronic fatigue syndrome. Scand J Rheumatol. 1993;22(1):35-8. http://www.ncbi.nlm.nih.gov/pubmed/8434245

 

Taking exception to chronic fatigue syndrome prevalence findings by Price, et al.

Comment on: Estimating the prevalence of chronic fatigue syndrome and associated symptoms in the community. [Public Health Rep. 1992]

 

We would like to address some serious methodological issues in the article, “Estimating the Prevalence of Chronic Fatigue Syndrome and Associated Symptoms in the Community,” by Rumi K. Price, et al., published in the September-October issue of Public Health Reports. We believe that because of the deficiencies in the design of this research, the authors’ conclusions are totally illogical and invalid.

In this article, the authors conclude that Chronic Fatigue Syndrome (CFS), as defined by the Centers for Disease Control (CDC) Diagnostic Criteria, might be “quite rare” in the general population, as only 1 of 13,538 individuals studied was deemed to have CFS. The official CDC Diagnostic Criteria, however, were not utilized to diagnose cases of CFS. Instead, the researchers reviewed interview questionnaire data collected between 1981 and 1984 for a purpose unrelated to diagnosing CFS. In fact, the CDC Diagnostic Criteria were not formulated and published until 1988.

You can read the rest of this comment as well as the rely from the authors here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1403345/pdf/pubhealthrep00069-0137c.pdf

 

Source: Robin R, Lipkin DM, Hume GW. Taking exception to chronic fatigue syndrome prevalence findings by Price, et al. Public Health Rep. 1993 Jan-Feb;108(1):135-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1403345/

 

Psychotropic treatment of chronic fatigue syndrome and related disorders

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) and fibromyalgia frequently are associated with symptoms of major depression. For this reason, antidepressants have been used in treatment of these disorders; however, little direction has been provided into this application in psychopharmacology.

METHOD: First, nine studies were reviewed regarding the relationship of the symptoms of fatigue and depression. Next, 23 reports (12 double-blind studies, 7 open studies, and 4 case reports) were reviewed for the effectiveness of therapy as assessed by global response and improvement of both depression and pain. Studies were differentiated by type of controls, as well as by alleged mechanism of action of the pharmacologic agent.

RESULTS: Disturbances in brain neurochemistry shared by CFS and major depression may serve as a basis for the effectiveness of some antidepressants in CFS. Response to some antidepressants in patients with CFS or fibromyalgia may occur at doses lower than those used in major depression, e.g., amitriptyline 25-75 mg/day. We further found that the more serotonergic treatments (e.g., clomipramine) were more successful in alleviating pain than depression, whereas catecholaminergic agents (e.g., maprotiline, bupropion) seemed particularly effective for symptoms of associated depression.

CONCLUSION: To maximize response of the physiologic and psychological consequences of the disorder, more investigation is needed to replicate the apparent findings that relate the neurochemical impairment underlying CFS and fibromyalgia to the type of antidepressant mechanism.

 

Source: Goodnick PJ, Sandoval R. Psychotropic treatment of chronic fatigue syndrome and related disorders. J Clin Psychiatry. 1993 Jan;54(1):13-20. http://www.ncbi.nlm.nih.gov/pubmed/8428892

 

Central basis of muscle fatigue in chronic fatigue syndrome

Abstract:

We studied whether muscle fatigue, metabolism, or activation are abnormal in the chronic fatigue syndrome (CFS). Subjects performed both an intermittent submaximal and a sustained maximal voluntary isometric exercise protocol of the tibialis anterior muscle.

The extent of fatigue, metabolic response, and changes in both M-wave amplitude and twitch tension during exercise were similar in patients and controls. The response to systemic exercise was also normal in the patients. However, voluntary activation of the tibialis was significantly lower in the patients during maximal sustained exercise.

The results indicate that patients with CFS have (1) normal fatigability and metabolism at both the intracellular and systemic levels, (2) normal muscle membrane function and excitation-contraction coupling, and (3) an inability to fully activate skeletal muscle during intense, sustained exercise. This failure of activation was well in excess of that found in controls, suggesting an important central component of muscle fatigue in CFS.

Comment in: Chronic fatigue syndrome. [Neurology. 1993]

 

Source: Kent-Braun JA, Sharma KR, Weiner MW, Massie B, Miller RG. Central basis of muscle fatigue in chronic fatigue syndrome. Neurology. 1993 Jan;43(1):125-31. http://www.ncbi.nlm.nih.gov/pubmed/8423875