2003 – Page 9 – American ME and CFS Society

Psychiatric morbidity in the chronic fatigue syndrome: are patients with personality disorder more physically impaired?

Abstract:

OBJECTIVE: The long-term consequences of chronic fatigue syndrome (CFS) include substantial impairment in physical functioning and high levels of work disability. In the absence of a medical explanation for this impairment, some have speculated that it may be due to comorbid psychiatric illness or personality disorder. We addressed this possibility by comparing the functional status of three CFS groups: no psychiatric diagnosis, psychiatric illness only, psychiatric illness and personality disorder. A second aim of the study was to determine whether a continuous measure of psychological distress could provide a better account of impairment than psychiatric diagnosis.

METHOD: The study sample consisted of 84 consecutive female referrals with CFS. All participants satisfied the case definition and completed an assessment protocol consisting of: physical examination, psychiatric interview and self-report questionnaires.

RESULTS: Psychiatric illness, either alone or in combination with a comorbid personality disorder, was not associated with physical impairment or disability in female participants. A regression model of physical functioning found that psychological distress accounted for 6% and symptom severity for 41% of the variance (P=.06 and <.01, respectively). In the case of disability, the corresponding percentages were 2% and 18% (NS and P<.01, respectively). The modest effects of psychological distress could not be attributed to symptom severity.

CONCLUSIONS: Although psychiatric illness and personality disorder was prevalent, neither could explain the effects of CFS on physical functioning and disability. As yet, there is no psychological or medical explanation for the behavioral consequences of CFS.

Source: Ciccone DS, Busichio K, Vickroy M, Natelson BH. Psychiatric morbidity in the chronic fatigue syndrome: are patients with personality disorder more physically impaired? J Psychosom Res. 2003 May;54(5):445-52. http://www.ncbi.nlm.nih.gov/pubmed/12726901

Childhood experiences of illness and parenting in adults with chronic fatigue syndrome

Abstract:

OBJECTIVE: There are many similarities between chronic fatigue syndrome (CFS), the somatoform disorders and problems otherwise known as “medically unexplained symptoms.” There is some evidence to suggest that a combination of inadequate parenting and early illness experience may predispose the individual to develop medically unexplained symptoms in adult life. The aim of this investigation was to compare the contributions of childhood experiences of illness and parenting in adults with CFS with a fracture clinic control group.

METHOD: A retrospective case control design was used. Thirty patients with a diagnosis of CFS and 30 patients attending a fracture clinic in an inner London teaching hospital completed questionnaires measuring parental care and protection and were interviewed about childhood experiences of illness.

RESULTS: There were no differences in childhood experience of illness in the two groups. However, logistic regression revealed that maternal overprotection and depression were associated with the diagnosis of CFS.

CONCLUSION: The findings may represent risk factors for the development of CFS in adult life. It is possible that maternal overprotection in particular is related to the formation of belief systems about avoiding activity that operate to adversely influence behaviour in patients with CFS.

Source: Fisher L, Chalder T. Childhood experiences of illness and parenting in adults with chronic fatigue syndrome. J Psychosom Res. 2003 May;54(5):439-43. http://www.ncbi.nlm.nih.gov/pubmed/12726900

Review: cognitive behavioural interventions may be effective for chronic fatigue syndrome and chronic back pain

Comment on: Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care? [BMJ. 2002]

Psychological disorders have a high financial burden with many indirect costs. Behavioural strategies and cognitive behavioural interventions may be effective for a range of mental disorders, including some of the most chronic, severe and costly mental health problems.1 Very few medical professionals are adequately trained to deliver such treatments, however. This article is both timely and important because it emphasises the need to disseminate cognitive behaviour therapies more widely.

Raine et al conducted a thorough review of the efficacy of psychological treatments for common somatic symptoms: chronic fatigue syndrome, irritable bowel syndrome and chronic back pain. The results were consistent with the findings by the American Psychological Association’s Task Force on Promotion and Dissemination of Psychological Procedures:2 cognitive behaviour interventions and behaviour therapy are effective for treating chronic back pain and chronic fatigue syndrome. Raine et al found that treatment effects were stronger in secondary care compared with primary care settings. Furthermore, antidepressants were effective in both settings for treating irritable bowel syndrome.

The review has some limitations. First, as in all secondary analyses, the review is based only on published studies (that are more likely to report positive outcomes). There may also be problems with how interventions were defined and implemented. The majority of studies did not follow a treatment manual and did not measure adherence to the therapy protocol. The distinction between “behaviour therapy” and “cognitive-behaviour therapy” therefore remains elusive. This leaves important questions unanswered about how and why these treatments work (ie the mechanisms and mediators of change).3

You can read the rest of this comment here: http://ebmh.bmj.com/content/6/2/55.long

Source: Hofmann SG. Review: cognitive behavioural interventions may be effective for chronic fatigue syndrome and chronic back pain. Evid Based Ment Health. 2003 May;6(2):55. http://ebmh.bmj.com/content/6/2/55.long (Full article)

Psychometric properties of the Dutch Chronic Fatigue Syndrome–Activities and Participation Questionnaire (CFS-APQ)

Abstract:

BACKGROUND AND PURPOSE: The Chronic Fatigue Syndrome-Activities and Participation Questionnaire (CFS-APQ) is a recently developed disease-specific assessment tool for monitoring activity limitations and participation restrictions in patients with chronic fatigue syndrome (CFS). In this study, the convergent validity, content validity, and test-retest reliability of data obtained with the Dutch-language version of the questionnaire were examined.

SUBJECTS AND METHODS: One hundred eleven consecutive patients with CFS were enrolled, of whom 47 fulfilled all inclusion criteria. The subjects were first asked to rate their pain, fatigue, and ability to concentrate using 3 visual analog scales, to list at least 5 activities that had become difficult to perform due to their complaints, and to complete the CFS-APQ. Furthermore, subjects were asked to complete a modified version of the CFS-APQ at home and return it to the investigators. The content of the questionnaire was reviewed using the World Health Organization’s International Classification of Impairments, Disability and Health (ICIDH) beta II draft. Spearman rank correlation coefficients (R) were used for the convergent validity analysis, and intraclass correlation coefficients were computed for the assessment of the test-retest data.

RESULTS: Overall scores on the CFS-APQ correlated with the scores from the visual analog scales for pain (R=.51, P<.001) and fatigue (R=.50, P<.001). The majority of the responses (157 out of 183 answers [85.8%]) to the request to “list difficult activities” matched the content of the CFS-APQ. Using the ICIDH beta II draft, 21 out of 26 questions were found to address activities, and the remaining 5 questions measured the participation level. The Cronbach alpha coefficient was.94, and intraclass correlation coefficients for test-retest reliability of the overall scores were >or= .95 (P<.001).

DISCUSSION AND CONCLUSION: The results substantiate the convergent validity, content validity, and reliability of the CFS-APQ scores for patients with CFS.

Source: Nijs J, Vaes P, McGregor N, Van Hoof E, De Meirleir K. Psychometric properties of the Dutch Chronic Fatigue Syndrome–Activities and Participation Questionnaire (CFS-APQ). Phys Ther. 2003 May;83(5):444-54. http://ptjournal.apta.org/content/83/5/444.long (Full article)

Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome

Abstract:

BACKGROUND: There is a growing body of evidence supporting the theory that problems with immune function play an important role in chronic fatigue syndrome (CFS).

METHODS: We studied 90 CFS cases and 50 healthy controls from two different areas of upstate New York to determine whether there were differences in the absolute number and pattern of natural killer (NK) and cytotoxic T-cell phenotypes between CFS cases and healthy controls in the two regions. One group was from a small town where a cluster of cases existed; the other was from a large metropolitan area where there was not a known cluster.

RESULTS: The number of CD56+CD3+CD8+ and CD56+CD3+CD8- cells in cases from the two areas were both significantly elevated over that of controls from the metropolitan area (P < 0.03). The number of CD56+CD3-CD8+ and CD56+CD3-CD8- cells was significantly reduced in the two case groups compared to that of controls from the metropolitan area (P = 0.04). However, controls who were from the same town as the cluster cases had numbers of CD56+CD3+CD8+, CD56+CD3+CD8-, and CD56+CD3-CD8- cells that were more like that of cases than controls. Only the number of CD56+CD3-CD8+ cells (an NK cell subset) was significantly different in cases versus controls from the cluster area (P = 0.022).

CONCLUSIONS: These data suggest that differences in controls from cluster and noncluster areas may be responsible for some of the inconsistencies in results from other studies. Furthermore, they suggest the possibility that NK cell function may play an important role in preventing the development of CFS in individuals who live in a community where a cluster of cases have been identified.

Source: Stewart CC, Cookfair DL, Hovey KM, Wende KE, Bell DS, Warner CL. Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome. Cytometry B Clin Cytom. 2003 May;53(1):26-33. http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.10034/full (Full article)

Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome

Abstract:

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.

Source: Kerr JR, Cunniffe VS, Kelleher P, Bernstein RM, Bruce IN. Successful intravenous immunoglobulin therapy in 3 cases of parvovirus B19-associated chronic fatigue syndrome. Clin Infect Dis. 2003 May 1;36(9):e100-6. Epub 2003 Apr 22. http://cid.oxfordjournals.org/content/36/9/e100.long (Full article)

The investigation of chronic fatigue syndrome: a case-study of the limitations of inductive inferences and non-falsifiable hypotheses in medical research

Abstract:

Karl Popper’s argument that deductive logic and falsifiable hypotheses are necessary for the growth of scientific knowledge has been controversial. One approach to assess the relevance of his ideas to medical science has been to evaluate examples of successful research. Another approach is to analyze an unsuccessful investigation. The inconclusive search for a unique ‘chronic fatigue syndrome’ offers a well-documented case-study for this analysis. Over the past 130 years, numerous studies have provided clinical and epidemiological data, which have supported competing hypotheses about the etiology of chronic fatigue. However, few hypotheses have been refuted because it has not been possible to establish objective standards of inquiry for a subjective symptom like fatigue. As a result, intensive research efforts have not converged on correct explanations by eliminating erroneous ideas. This unsuccessful investigation illustrates how non-falsifiable hypotheses are insufficient to advance medical knowledge, even when there is an abundance of empirical data.

Source: Hyams KC. The investigation of chronic fatigue syndrome: a case-study of the limitations of inductive inferences and non-falsifiable hypotheses in medical research. Med Hypotheses. 2003 May;60(5):760-6. http://www.ncbi.nlm.nih.gov/pubmed/12710915

Chronic fatigue syndrome: new evidence for a central fatigue disorder

Abstract:

Considerable evidence points towards a prominent role for central nervous system (CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited exercise and subsequent recovery.

Groups of 12 CFS patients and 11 age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance. Plasma amino acid concentrations, oxygen uptake and ratings of perceived exertion were measured at rest, and during exercise and recovery.

Peak oxygen uptake was significantly lower in the CFS patients compared with controls. Rating of perceived exertion in the patients was higher at all time points measured, including at rest, relative to controls. Levels of free tryptophan (free Trp), the rate-limiting 5-HT precursor, were significantly higher in CFS patients at exhaustion and during recovery, whereas concentrations of branched-chain amino acids (BCAA) and large neutral amino acids (LNAA) were lower in CFS patients at exhaustion, and for LNAA also during recovery. Consequently, the [free Trp]/[BCAA] and [free Trp]/[LNAA] ratios were significantly higher in CFS patients, except at rest.

On the other hand, levels of tyrosine, the rate-limiting dopaminergic precursor, were significantly lower at all time points in the CFS patients. The significant differences observed in a number of key putative CNS 5-HT and dopaminergic modulators, coupled with the exacerbated perception of effort, provide further evidence for a potentially significant role for CNS mechanisms in the pathogenesis of CFS.

Source: Georgiades E, Behan WM, Kilduff LP, Hadjicharalambous M, Mackie EE, Wilson J, Ward SA, Pitsiladis YP. Chronic fatigue syndrome: new evidence for a central fatigue disorder. Clin Sci (Lond). 2003 Aug;105(2):213-8. http://www.ncbi.nlm.nih.gov/pubmed/12708966

The head-up tilt test for diagnosing chronic fatigue syndrome

Comment on: The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. [QJM. 2003]

Sir,

The recent paper by Naschitz et al. on the use of the head‐up tilt test with haemodynamic instability score (HIS) in the diagnosis of chronic fatigue syndrome (CFS) provides additional insight about the role of dysautonomia in the pathogenesis of CFS. We would like to raise some points regarding the patient group studied.

The enrolment of clinically‐diagnosed CFS patients and the awareness of diagnosis by technicians prior to performing the tilt test, could result in selection bias. Additionally, generalizing the result of the study, whose population was rich in patients with CFS (40/349, or 11%) to the general population (prevalence of CFS 0.07–0.2%) could be misleading. Using their results of a sensitivity of 90.3% and specificity of 84.5% for a cutoff of HIS >−0.98, a positive head‐up tilt test in a patient presenting with fatigue in the general population would have a positive predictive value of only 0.37–1.15. This result, taken with the fact that around one‐fifth of the patients developed a presyncopal or syncopal episode, would make the test less appealing to patients. However, in a patient presenting with fatigue where clinical diagnosis remained unclear despite lengthy evaluation, the head‐up tilt test could be useful for narrowing down the range of diagnoses.

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/96/5/379.2.long

Source: Ghosh AK, Ghosh K. The head-up tilt test for diagnosing chronic fatigue syndrome. QJM. 2003 May;96(5):379-80. http://qjmed.oxfordjournals.org/content/96/5/379.2.long (Full article)

The neuroendocrinology of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a common and disabling problem; although most likely of biopsychosocial origin, the nature of the pathophysiological components remains unclear. There has been a wealth of interest in the endocrinology of this condition, which will be reviewed in this article. Most studied has been the hypothalamic-pituitary-adrenal (HPA) axis; although the quality of many studies is poor, the overall balance of evidence points to reduced cortisol output in at least some patients, with some evidence that this is linked to symptom production or persistence.

There is evidence for heightened negative feedback and glucocorticoid receptor function and for impaired ACTH and cortisol responses to a variety of challenges. However, there is no evidence for a specific or uniform dysfunction of the HPA axis. Given the many factors that may impinge on the HPA axis in CFS, such as inactivity, sleep disturbance, psychiatric comorbidity, medication, and ongoing stress, it seems likely that HPA axis disturbance is heterogeneous and of multifactorial etiology in CFS. Studies assessing GH, dehydroepiandrostenedione and its sulfate, melatonin, leptin, and neuroendocrine-monoamine interactions are also reviewed.

There is some evidence from these studies to suggest alterations of dehydroepiandrostenedione sulfate function and abnormal serotonin function in CFS, but whether these changes are of functional importance remains unclear. To obtain a clearer assessment of the etiological and pathophysiological relevance of endocrine changes in CFS, it is suggested that more prospective cohort studies be undertaken in groups at high risk for CFS, that patients with CFS are followed up into recovery, and that multidimensional assessments are undertaken to unravel the influence of the various confounding factors on the observed endocrine changes in CFS.

Source: Cleare AJ. The neuroendocrinology of chronic fatigue syndrome. Endocr Rev. 2003 Apr;24(2):236-52. http://www.ncbi.nlm.nih.gov/pubmed/12700181