Contrasting neuroendocrine responses in depression and chronic fatigue syndrome

Abstract:

Hypothalamic-pituitary-adrenal (HPA) axis and central 5-HT function were compared in chronic fatigue syndrome (CFS), depression and healthy states. 10 patients with CFS and 15 patients with major depression were matched for age, weight, sex and menstrual cycle with 25 healthy controls.

Baseline-circulating cortisol levels were highest in the depressed, lowest in the CFS and intermediate between the two in the control group (P = 0.01). Prolactin responses to the selective 5-HT-releasing agent d-fenfluramine were lowest in the depressed, highest in the CFS and intermediate between both in the healthy group (P = 0.01). Matched pair analysis confirmed higher prolactin responses in CFS patients than controls (P = 0.05) and lower responses in depressed patients than controls (P = 0.003). There were strong inverse correlations between prolactin and cortisol responses and baseline cortisol values.

These data confirm that depression is associated with hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.

 

Source: Cleare AJ, Bearn J, Allain T, McGregor A, Wessely S, Murray RM, O’Keane V. Contrasting neuroendocrine responses in depression and chronic fatigue syndrome. J Affect Disord. 1995 Aug 18;34(4):283-9. http://www.ncbi.nlm.nih.gov/pubmed/8550954

 

Cell-mediated immune function and the outcome of chronic fatigue syndrome

Abstract:

This study examined the importance of cell-mediated immunity in determining the long-term outcome of patients diagnosed with chronic fatigue syndrome (CSF).

A total of 103 patients (74%) of 139 previously enrolled in one of two treatment trials conducted within a university hospital referral center was reviewed a mean of 3.2 yr after trial entry. Ongoing symptom severity, levels of disability and immunological function were assessed at follow-up. The relationship between immunological function at trial entry and measures of outcome was also evaluated.

Sixty-five patients (63%) had improved, while only 6 (6%) reported no current symptoms. Thirty-one subjects (30%) were unable to perform any form of work and 26 (25%) were on a disability benefit directly attributable to CFS. Cell-mediated immune function, as measured at trial entry or follow-up, did not appear to affect outcome.

Whilst improvement occurred in the majority of patients with CFS, a substantial proportion (37%) remained functionally impaired. Impairment of cell-mediated immunological function measured during the course of the illness may not be an important factor in determining long-term outcome.

 

Source: Wilson A, Hickie I, Lloyd A, Hadzi-Pavlovic D, Wakefield D. Cell-mediated immune function and the outcome of chronic fatigue syndrome. Int J Immunopharmacol. 1995 Aug;17(8):691-4. http://www.ncbi.nlm.nih.gov/pubmed/8847164

 

Are cytokines associated with neuropsychiatric syndromes in humans?

Abstract:

Traditional aetiological models in neuropsychiatry have placed little emphasis on the abnormal behavioural responses (decreased psychomotor activity, anorexia, weight loss, decreased social exploration and sexual behaviour, impaired cognitive function and increased somnolence) that are common to both psychiatric syndromes, notably depression, and the illness behaviour of sick animals.

In recent years, the possible role of cytokines, as mediators of not only the immunological and metabolic responses to infection and inflammation but also a co-ordinated behavioural response, has been described. Further, a range of possible mechanisms for these effects has been postulated, notably involving corticotropin releasing factor (CRF) and prostaglandins of the E series (PgE) with the central nervous system (CNS).

Here we outline a series of human clinical conditions where neuropsychiatric syndromes co-occur with a host response to infection or inflammation. These may be characterized by cytokine production (e.g. acute, recurrent and chronic viral illness, systemic autoimmune diseases and chronic fatigue syndrome).

Other clinical situations characterized by exposure to or in vivo production of cytokines (e.g. treatment of chronic infections and malignancies, progression and/or recurrence of malignancies) are also discussed.

We postulate that the stereotyped behavioural repertoire observed is mediated by cytokine-dependent mechanisms within the CNS. Systematic studies of the behavioural responses of such patient groups are suggested, noting specifically correlations between the time course and severity of immune and neuroendocrine and behavioural responses and dose-response effects.

 

Source: Hickie I, Lloyd A. Are cytokines associated with neuropsychiatric syndromes in humans? Int J Immunopharmacol. 1995 Aug;17(8):677-83. http://www.ncbi.nlm.nih.gov/pubmed/8847162

 

Chronic fatigue syndrome. Committee for Science and Education, Medical Association of South Africa

Abstract:

OBJECTIVE: To acknowledge the clinical syndrome chronic fatigue syndrome (CFS) and outline the diagnostic criteria and reasonable management.

OUTCOMES: Attempt at containment of treatment cost and improvement of the quality of care of patients with CFS.

EVIDENCE: Delphi-type commentary from 20 expert clinicians and appropriate organisations. Limited literature survey.

VALUES: To clarify the reasonable management of CFS amid conflicting clinical opinion on a condition of concern to patients, funders and doctors. An adaptation of an existing guideline was sent to organisations and individuals for comment. Comments received were included in this guideline where possible.

BENEFITS, HARMS AND COSTS. To acknowledge a clinical syndrome with a reasonable approach to management considering the cost implications. No cost analysis was done.

RECOMMENDATIONS: To recommend the following: (i) diagnostic criteria for CFS; (ii) potential differential diagnoses and possible investigations; and (iii) management protocol.

VALIDATION: The draft guidelines were subjected to external review by individual doctors who are acknowledged CFS treaters, doctor groups and the patient support group. There were major disputes about the content, with the responses falling into two groups: those who do not believe CFS is a distinguishable illness, and those who do.

DEVELOPER AND FUNDING: The Committee for Science and Education, Medical Association of South Africa.

ENDORSEMENTS: Medical Association of South Africa and national health care organisations (see list at the end of the document).

Comment in: Committee to investigate chronic fatigue syndrome. [S Afr Med J. 1996]

 

Source: Chronic fatigue syndrome. Committee for Science and Education, Medical Association of South Africa. S Afr Med J. 1995 Aug;85(8):780-2. [No authors listed] http://www.ncbi.nlm.nih.gov/pubmed/8553151

 

Estimating rates of chronic fatigue syndrome from a community-based sample: a pilot study

Abstract:

Most of the Chronic Fatigue Syndrome (CFS) epidemiological studies have relied on physicians who refer patients having at least six months of chronic fatigue and other symptoms. However, there are a number of potential problems when using this method to derive prevalence statistics.

For example, some individuals with CFS might not have the economic resources to access medical care. Other individuals with CFS might be reluctant to use medical personnel, particularly if they have encountered physicians skeptical of the authenticity of their illness. In addition, physicians that are skeptical of the existence of CFS might not identify cases.

In the present pilot study, a random community sample (N = 1,031) was interviewed by telephone in order to identify and comprehensively evaluate individuals with symptoms of CFS and those who self-report having CFS. Different definitions of CFS were employed, and higher rates (0.2%) of CFS were found than in previous studies. Methodological benefits in using more rigorous epidemiological methods when estimating CFS prevalence rates are discussed.

 

Source: Jason LA, Taylor R, Wagner L, Holden J, Ferrari JR, Plioplys AV, Plioplys S, Lipkin D, Papernik M. Estimating rates of chronic fatigue syndrome from a community-based sample: a pilot study. Am J Community Psychol. 1995 Aug;23(4):557-68. http://www.ncbi.nlm.nih.gov/pubmed/8546110

 

Gait abnormalities in chronic fatigue syndrome

Abstract:

To evaluate our clinical impression that patients with the chronic fatigue syndrome (CFS) did not walk normally, we assessed gait kinematics at slow walking speeds (i.e., 0.45, 0.89 and 1.34 m/sec) and 30 m run time speeds on CFS patients and on a comparison group of sedentary controls.

Run time was significantly slower for CFS than control subjects (p < 0.001). There was a significant interaction (p < 0.01) between group and speed for maximum hip angle during stance and swing phase with hip angle being significantly larger at 1.34 m/sec for CFS than controls subjects for both cases (p < 0.05). Knee flexion during stance and swing phases was significantly larger for controls than CFS subjects at 0.45 m/sec (p < 0.01). Ratio of stride length divided by leg length was significantly larger for the control subjects than for the CFS subjects with differences occurring at 0.45 and 0.89 m/sec (p < 0.01) but not 1.34 m/sec.

The data indicate that CFS patients have gait abnormalities when compared to sedentary controls. These could be due to balance problems, muscle weakness, or central nervous system dysfunction; deciding which will require further research. Evaluation of gait may be a useful tool to measure outcome following therapeutic interventions.

 

Source: Boda WL, Natelson BH, Sisto SA, Tapp WN. Gait abnormalities in chronic fatigue syndrome. J Neurol Sci. 1995 Aug;131(2):156-61. http://www.ncbi.nlm.nih.gov/pubmed/7595641

 

Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients

Abstract:

Coxsackie B enteroviruses have been implicated repeatedly as agents associated with chronic fatigue syndrome (CFS). The objective of this study was to compare the serological evidence for the presence of Coxsackie B virus neutralising antibody, with the polymerase chain reaction (PCR) detecting a portion of the 5′ nontranslated region (NTR) of the enterovirus genome.

Serum samples from 100 chronic fatigue patients and from 100 healthy comparison patients were used in this study. In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group. Using the neutralisation assay, 34% of study patients were positive, compared to 41% of comparison patients.

In the study group, 66/100 patient results correlated, i.e., they were either positive/positive or negative/negative for both tests. Of those that did not correlate, the majority were PCR-positive/Coxsackie B antibody-negative (21/34).

In the comparison group, 58/100 patient results correlated. Of those that did not, the majority were PCR-negative/Coxsackie B antibody-positive (37/42).

The Coxsackie B antibody neutralisation assay was not able to differentiate the CFS study group from the healthy comparison group, and thus the clinical relevance of this assay may be questioned. The PCR assay did differentiate the two groups with significantly more CFS patients having evidence of enterovirus than the comparison group.

Source: Nairn C, Galbraith DN, Clements GB. Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients. J Med Virol. 1995 Aug;46(4):310-3. http://www.ncbi.nlm.nih.gov/pubmed/7595406

 

Patients with a self diagnosis of myalgic encephalomyelitis

Comment in: Patients with a self diagnosis of myalgic encephalomyelitis. [BMJ. 1995]

 

EDITOR,-Myalgic encephalomyelitis is most commonly related to an underlying psychological or psychiatric disturbance.’2 Shonagh Scott and colleagues report that when general practitioners deal with symptoms consistent with those of myalgic encephalomyelitis their attitude is likely to be influenced by the patient’s perception, expectations, and social class.’ It is not uncommon for patients to diagnose myalgic encephalomyelitis themselves before they seek a consultation; this can lead to disruption of the doctor-patient relationship, unsatisfactory consultations, and possibly failure to diagnose any underlying pathological process. We report on a patient with a self diagnosis of myalgic encephalomyelitis in whom hypopituitarism was diagnosed only after a protracted period

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550388/pdf/bmj00603-0061a.pdf

Comment on:

Population based study of fatigue and psychological distress. [BMJ. 1994]

Professional and popular views of chronic fatigue syndrome. [BMJ. 1994]

 

Source: Hurel SJ, Abuiasha B, Baylis PH, Harris PE. Patients with a self diagnosis of myalgic encephalomyelitis. BMJ. 1995 Jul 29;311(7000):329. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2550388/pdf/bmj00603-0061a.pdf (Full comment)

 

Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system

Abstract:

OBJECTIVES: To investigate the point prevalence of the chronic fatigue syndrome and unexplained debilitating chronic fatigue in a community-based sample of persons and to describe demographic, clinical, and psychosocial differences among those with the chronic fatigue syndrome, those with chronic fatigue, and healthy controls.

DESIGN: Prospective cohort study.

SETTING: A health maintenance organization in Seattle, Washington.

PARTICIPANTS: A random sample of 4000 members of the health maintenance organization was surveyed by mail for the presence of chronic fatigue.

MEASUREMENTS: Persons with chronic fatigue were evaluated using a questionnaire that requested information about medical history and fatigue and related symptoms; validated measures of functional status and psychological distress; a physical examination; and standardized blood tests. A structured psychiatric interview was done in persons who appeared to meet the original Centers for Disease Control and Prevention (CDC) criteria for the chronic fatigue syndrome. Participants completed self-report measures at 12 and 24 months. Those with chronic fatigue were reevaluated in person 1 year after study enrollment.

RESULTS: 3066 (77%) of the 4000 members surveyed responded. Chronic fatigue was reported by 590 persons (19%). Of these, 388 (66%) had a medical or psychiatric condition that could account for the fatigue. Of the 74 persons (37%) with chronic fatigue who were enrolled in the study, only 3 met the CDC criteria for the chronic fatigue syndrome. The remaining 71 persons were designated as having chronic fatigue alone. Seventy-four healthy, age- and sex-matched controls who were drawn from the same sample but who denied having chronic fatigue were also studied. Demographic characteristics were similar in persons with the chronic fatigue syndrome, persons with chronic fatigue alone, and controls. Those with the chronic fatigue syndrome or chronic fatigue alone had more frequent cervical and axillary adenopathy, poorer functional status, and greater psychological distress than controls. Women and minorities were not overrepresented among cases with chronic fatigue.

CONCLUSIONS: Using different assumptions about the likelihood that persons who did not participate in the study had the chronic fatigue syndrome, the estimated crude point prevalence of the syndrome in this community ranged from 75 to 267 cases per 100,000 persons. The point prevalence of chronic fatigue alone was strikingly higher; it ranged from 1775 to 6321 cases per 100,000 persons.

 

Source: Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff AL. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med. 1995 Jul 15;123(2):81-8. http://www.ncbi.nlm.nih.gov/pubmed/7778839

 

African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome

Abstract:

BACKGROUND: A cytomegalovirus-like ‘stealth virus’ had previously been isolated from a patient with the chronic fatigue syndrome (CFS).

OBJECTIVE: To determine the original derivation of this virus.

STUDY DESIGN: DNA sequencing of cloned regions of the virus was performed and the sequences were compared using BLASTN and FASTA analyses against the entire GenBank database. Viral sequences were also used to design primers for the polymerase chain reaction (PCR).

RESULTS: DNA and amino acid sequence comparisons showed that the stealth virus was more closely related to the Colburn strain of simian cytomegalovirus (SCMV) than to CMV of either human or rhesus monkey origin or to any other sequenced herpesvirus. Similarity, but non-identity, between the stealth virus and SCMV, was confirmed using PCR.

CONCLUSION: The findings implicate the African green monkey as the probable source of the virus isolated from this CFS patient.

 

Source: Martin WJ, Ahmed KN, Zeng LC, Olsen JC, Seward JG, Seehrai JS. African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome. Clin Diagn Virol. 1995 Jul;4(1):93-103. http://www.ncbi.nlm.nih.gov/pubmed/15566831