Neurobiology of chronic fatigue syndrome

Abstract:

1. Chronic fatigue syndrome (CFS) is characterized by a new onset of significant fatigue for a period of six months or longer usually following an infection, injury or period of high stress.

2. The exact etiology of CFS is not known and a diagnostic test is not available. Hence, the diagnosis is made by exclusion of other explanations for the patient’s symptoms and by meeting the CDC research case definitions. Early studies supported an infectious or immune dysregulation hypothesis for the pathophysiology of CFS.

3. Subsequent studies documented that neurological, affective and cognitive symptoms also occur at high rates in CFS patients. Neuropsychological, neuroendocrine studies and brain imaging have now confirmed the occurrence of neurobiological abnormalities in most patients with CFS.

4. In this article, the authors review these findings in relation to the clinical neurobiology of CFS and their potential relevance to biological psychiatry.

 

Source: Gonzalez MB, Cousins JC, Doraiswamy PM. Neurobiology of chronic fatigue syndrome. Prog Neuropsychopharmacol Biol Psychiatry. 1996 Jul;20(5):749-59. http://www.ncbi.nlm.nih.gov/pubmed/8870062

 

Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome

Abstract:

Many patients with chronic fatigue syndrome (CFS) display features of hypothalamic dysfunction. We have investigated aspects of circadian rhythmicity, an important hypothalamic function, in 20 CFS patients and in 17 age- and sex-matched healthy control subjects.

There were no differences between the two groups in the amplitude, mesor (mean value) or timing of the peak (acrophase) of the circadian rhythm of core temperature, or in the timing of the onset of melatonin secretion.

However, the CFS patients showed no significant correlation between the timing of the temperature acrophase and the melatonin onset (P < 0.5), whereas the normal significant correlation was observed in the controls (P < 0.05). Dissociation of circadian rhythms could be due to the sleep deprivation and social disruption, and/or the reduction in physical activity which typically accompany CFS.

By analogy with jet-lag and shift-working, circadian dysrhythmia could be an important factor in initiating and perpetuating the cardinal symptoms of CFS, notably tiredness, impaired concentration and intellectual impairment.

 

Source: Williams G, Pirmohamed J, Minors D, Waterhouse J, Buchan I, Arendt J, Edwards RH. Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome. Clin Physiol. 1996 Jul;16(4):327-37. http://www.ncbi.nlm.nih.gov/pubmed/8842569

 

Chronic fatigue in the community: ‘a question of attribution’

Abstract:

Thirty-eight subjects identified in a large community survey were found to attribute their fatigue to ‘myalgic encephalomyelitis’ (ME). They were matched randomly to two other groups of subjects who attributed their fatigue to either psychological or social factors. All three groups were followed up 18 months later and were asked to complete a series of questionnaires that examined fatigue, psychological distress, number of symptoms, attributional style and levels of disability.

At onset the ‘ME’ group were found to be more fatigued, had been tired for longer but were less psychologically distressed than the other two groups. At follow-up the ‘ME’ group were more handicapped in relation to home, work, social and private leisure activities, even when controlling for both duration of fatigue and fatigue at time 1, but were less psychologically distressed.

The relationships between psychological distress, specific illness attributions, attributional style and their effect on the experience of illness and its prognosis are discussed. Attributing fatigue to social reasons appears to be most protective.

 

Source: Chalder T, Power MJ, Wessely S. Chronic fatigue in the community: ‘a question of attribution’. Psychol Med. 1996 Jul;26(4):791-800. http://www.ncbi.nlm.nih.gov/pubmed/8817714

 

Depression in fatiguing illness: comparing patients with chronic fatigue syndrome, multiple sclerosis and depression

Abstract:

Because depression is commonly observed in the chronic fatigue syndrome (CFS), the present study sought to determine whether the symptom pattern is similar to that seen in clinically depressed subjects (DEP). Individuals with multiple sclerosis (MS) were chosen as an additional comparison group because MS is a fatiguing illness of known organic etiology. The Beck Depression Inventory (BDI) was used to compare categories of depressive symptomatology.

Absolute scores on the BDI were higher for the depressed group on mood and self-reproach symptoms, but were not higher than the CFS group on somatic and vegetative items. Analysis of symptoms as a percentage of total BDI score revealed no significant differences in mood or vegetative items among the three groups. The CFS and MS groups exhibited a significantly lower percentage of self-reproach symptoms than DEP, whereas the DEP group showed a lower percentage of somatic symptoms than the CFS and MS groups.

 

Source: Johnson SK, DeLuca J, Natelson BH. Depression in fatiguing illness: comparing patients with chronic fatigue syndrome, multiple sclerosis and depression. J Affect Disord. 1996 Jun 20;39(1):21-30. http://www.ncbi.nlm.nih.gov/pubmed/8835650

 

Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients have a urinary metabolite labeled CFSUM1 with increased incidence (P < 0.004) and relative abundance (P < 0.00003). The relative abundances of urinary CFSUM1 and beta-alanine were associated with alterations in metabolite excretion and symptom incidence.

In 20 CFS patients and 45 non-CFS subjects, symptom/metabolite associations were investigated by assessing symptom sensitivity and specificity, and symptom indices of total symptom incidence, CFS core symptoms, cognitive, neurological, musculoskeletal, gastrointestinal, infection-related and genitourinary symptom indices, as well as a visual analogue pain scale of average pain intensity. Thirty-three symptoms had significant (P < 0.005) sensitivity and specificity in the CFS patients compared to that in the non-CFS controls.

Severe fatigue was the only symptom with 100% sensitivity and specificity and CFSUM1 excretion was the primary metabolite for expression of this symptom. All nine symptom indices had elevated responses in the CFS patients (all P < 0.0000001). Multiple regression analyses indicated that all the symptom indices had significant correlations (R) with changes in the urinary excretion of metabolites (P < 0.0001).

CFSUM1 and beta-alanine were the first and second metabolites correlated with the CFS core symptom index and CFSUM1 was primarily associated with infection-related and musculoskeletal indices whereas beta-alanine was primarily associated with gastrointestinal and genitourinary indices. The strong associations of CFSUM1 and beta-alanine with CFS symptom expression provide a molecular basis for developing an objective test for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of the association between symptom expression and urinary metabolites in subjects with chronic fatigue syndrome. Biochem Mol Med. 1996 Jun;58(1):85-92. http://www.ncbi.nlm.nih.gov/pubmed/8809350

 

Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters

Abstract:

The potential relationships between chlorinated hydrocarbon contamination in human serum and red/white blood cell profiles were investigated by multivariate techniques to assess the cellular response patterns to high and low organochlorine levels in the serum.

Twenty-three healthy control subjects and fourteen patients with unexplained and persistent fatigue were divided on the basis of (a) high or low total organochlorine content, (b) high or low DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethene) content, and (c) high or low HCB (hexachlorobenzene) content. Discriminant function analysis revealed that the groups with high organochlorine content had significantly different red/white blood cell profiles compared with the low organochlorine groups ((a) P < 0.017, (b) P < 0.015, and (c) P < 0.0002). As a variable, the percentage of neutrophils was the most important discriminant parameter for differentiating between the high and low total organochlorine groups.

Thirteen of the fourteen fatigued patients were characterized as “high total organocholorine content” (P < 0.04). The red cell distribution width was elevated in the high DDE group (P < 0.04) and was the most important discriminant parameter for differentiating between the high and low DDE groups. The percentage of eosinophils and the hemoglobin content were both reduced in the high HCB group (P < 0.009,P < 0.003, respectively) and the percentage of eosinophils was the most important discriminant parameter for differentiating between the high and low HCB groups. Those patients with unexplained and persistent fatigue had significantly higher levels of DDE compared with the controls and had different specific blood cell responses to organochlorines compared with control subjects.

 

Source: Dunstan RH, Roberts TK, Donohoe M, McGregor NR, Hope D, Taylor WG, Watkins JA, Murdoch RN, Butt HL. Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters. Biochem Mol Med. 1996 Jun;58(1):77-84. http://www.ncbi.nlm.nih.gov/pubmed/8809349

 

Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan

Abstract:

In order to clarify the epidemiological features of chronic fatigue syndrome (CFS), a nationwide survey was conducted using the Japanese version of the CDC Criteria prepared by the CFS Research Group of Japan. All clinical departments of internal medicine, pediatrics, psychiatry and neurology at university hospitals and at ordinary hospitals with 200 or more beds were surveyed.

Major results were as follows: (1) Period prevalence adjusted for response rate was 0.85 (0.63 for males and 1.02 for females) per 100,000 population during the year 1992; (2) Based on the first and final dates of hospital visits, the prevalences on January 1 of 1992 and 1993 were 0.40 and 0.60 per 100,000 population, respectively, suggesting an increasing trend; (3) Reported new cases during 1992 were 301, and the response adjusted-incidence was estimated to be 0.46 per 100,000 person-years; (4) The proportion of post-infectious CFS cases was 14.8% for both sexes, and tended to be slightly higher among females than males, but was not related to age. Three clusterings of two cases were reported.

 

Source: Minowa M, Jiamo M. Descriptive epidemiology of chronic fatigue syndrome based on a nationwide survey in Japan. J Epidemiol. 1996 Jun;6(2):75-80. https://www.jstage.jst.go.jp/article/jea1991/6/2/6_2_75/_pdf (Full article)

 

Multiple chemical sensitivity disorder in patients with neurotoxic illnesses

Abstract:

The data of 466 subjects suffering from neurologic disorders which are suggested to be caused by neurotoxic agents in their environment retrospectively was evaluated and documented. Among these cases there were 151 subjects with symptoms of Multiple Chemical Sensitivity Disorder (MCSD). The relationship between the neurological health impairments and neurotoxic agents in the environment of these patients was characterised using five different categories (probable = A, possible = B, uncertain = C, unclarified = D, not probable = E). From the 466 patients 320 subjects (69%) could be assigned to the categories A and B, respectively.

Within theses 320 cases with chronic neurotoxic health impairments 136 subjects (79 females and 57 males) showed signs of MCSD. Age and gender of cases as well as duration and character of exposure to neurotoxic substances retrospectively were assessed from the explicit files of the patients, which had been made anonymous for this purpose. Frequency of characteristic symptoms of neurotoxicity were analysed. Results are given for patients with neurotoxic health impairments with MCSD (n = 136) and without MCSD (n = 184).

Neurotoxic substances which were used as indoor wood preservatives (mainly Pentachlorophenol and/or Lindane) were found to be the causative agents in 63% of the cases with neurotoxic health impairments and MCSD. Other important neurotoxic substances to which the patients were mainly exposed were organic solvents (25%), formaldehyde (15%), dental materials (15%), pyrethroides (13%), and other biocides (19%) (multiple exposures were possible). The time of exposure was calculated as being > or = 10 years for 55% of the patients with MCSD and for 50% of the group with neurotoxic health impairments but without MCSD.

Out of the 184 cases with neurotoxic health impairments but without MCSD there were 22%, and out of the 136 cases with MCSD there were 39% who showed all symptoms of chronic fatigue syndrome. 53% of the cases with MCSD had an allergic disposition compared to only 20% of the cases without MCSD.

This work is not a controlled epidemiological study but a retrospective documentation and evaluation of data related to environmental medicine. With the present documentation in this purely descriptive manner the proof of a causal relationship was not possible or intended. But because corresponding epidemiological studies are lacking, this documentation can give important information on characteristic features of Multiple Chemical Sensitivity Disorder and chronic neurotoxic health impairments. Such information is essential for planning and carrying out epidemiological studies urgently needed in this field.

Comment in:

Comment on K. Lohmann, Anke Pröhl, E. Schwarz. Multiple chemical sensitivity in patients with neurotoxic illnesses. Gesundheitswesen. 1997 [Article in German]

 

Source: Lohmann K, Pröhl A, Schwarz E. Multiple chemical sensitivity disorder in patients with neurotoxic illnesses. Gesundheitswesen. 1996 Jun;58(6):322-31. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/8766847

 

Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome

Abstract:

PURPOSE: To evaluate the aerobic power (as maximum volume of oxygen consumed [VO2 max]) of women with chronic fatigue syndrome (CFS).

PATIENTS AND METHODS: Twenty-one women with CFS and 22 sedentary healthy controls (CON) were studied at the CFS Cooperative Research Center Exercise Laboratory at the VA Medical Center, East Orange, New Jersey. Performance was measured on an incremental treadmill protocol walking to exhaustion. Expired gases were analyzed by a metabolic system, heart rate was recorded continuously, and ratings of perceived exertion (RPE) were taken at each workload. The groups were divided into those who achieved VO2 max (CFS-MAX and CON-MAX) and those who stopped at a submaximal level (CFS-NOMAX and CON-NOMAX) by using standard criteria.

RESULTS: Seventeen CON and 10 CFS subjects achieved VO2 max. The VO2 max (mL/kg/min) of the CFS-MAX (28.1 +/- 5.1) was lower than that of the CON-MAX (32.1 +/- 4.3, P = 0.05). The CFS-MAX achieved 98 +/- 11% of predicted VO2 max. The CFS group had a higher RPE at the same absolute workloads as controls (P < 0.01) but not the same relative workloads.

CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness.

Comment in:

Exercise limits in chronic fatigue syndrome. [Am J Med. 1997]

Graded exercise testing and chronic fatigue syndrome. [Am J Med. 1997]

 

Source: Sisto SA, LaManca J, Cordero DL, Bergen MT, Ellis SP, Drastal S, Boda WL, Tapp WN, Natelson BH. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. 1996 Jun;100(6):634-40. http://www.ncbi.nlm.nih.gov/pubmed/8678084

 

A national assessment of the service, support, and housing preferences by persons with chronic fatigue syndrome. Toward a comprehensive rehabilitation program

Abstract:

Persons with Chronic Fatigue Syndrome (PWCs) completed and returned by mail a brief survey of open- and closed-ended items designed to assess their utilization and preferences for a variety of services. A total of 984 middle-aged adults diagnosed with Chronic Fatique Syndrome (CFS) from across North America returned the survey. During the past 12 months, many of these PWCs reported utilization of a primary care physician, gynecologist, CFS specialist, and self-help group to assist in their recovery from CFS. Most PWCs believed it was important to educate both health-care practitioners and the general public about CFS. In terms of their desire for specific recovery needs, factor analysis of responses indicated that these PWCs preferred self-help/social support services and general advocacy services in the treatment of their illness. The implications of these results for developing rehabilitation programs for PWCs are discussed.

 

Source: Jason LA, Ferrari JR, Taylor RR, Slavich SP, Stenzel CL. A national assessment of the service, support, and housing preferences by persons with chronic fatigue syndrome. Toward a comprehensive rehabilitation program. Eval Health Prof. 1996 Jun;19(2):194-207. http://www.ncbi.nlm.nih.gov/pubmed/10186910