The relationship between prior psychiatric disorder and chronic fatigue: evidence from a national birth cohort study

Abstract:

BACKGROUND: Increased rates of psychiatric disorder have previously been reported in those diagnosed with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), although the direction of causation in this relationship has not been established. We aimed to test the hypothesis that individuals with self-reported CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms.

METHOD: A total of 5,362 participants were prospectively followed with various measures of personality, psychiatric disorder and fatigue levels collected over the first 43 years of their life. CFS/ME was identified through self-report during a semi-structured interview at age 53 years.

RESULTS: Thirty-four (1.1%) of the 3,035 subjects assessed at age 53 years reported a diagnosis of CFS/ME. CFS/ME was more common among females, but there was no association between CFS/ME and either social class, social mobility or educational level. Those with psychiatric illness between the ages of 15 and 36 years were more likely to report CFS/ME later in life with an odds ratio (OR, adjusted for sex) of 2.65 [95% confidence interval (CI) 1.26-5.57, p=0.01]. Increased levels of psychiatric illness, in particular depression and anxiety, were present prior to the occurrence of fatigue symptoms. There was a dose-response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME. Personality factors were not associated with a self-reported diagnosis of CFS/ME.

CONCLUSIONS: This temporal, dose-response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.

 

Source: Harvey SB, Wadsworth M, Wessely S, Hotopf M. The relationship between prior psychiatric disorder and chronic fatigue: evidence from a national birth cohort study. Psychol Med. 2008 Jul;38(7):933-40. Epub 2007 Nov 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196526/ (Full article)

 

Possible use of repeated cold stress for reducing fatigue in chronic fatigue syndrome: a hypothesis

Abstract:

BACKGROUND: Physiological fatigue can be defined as a reduction in the force output and/or energy-generating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity. A typical example of a fatigue-related disorder is chronic fatigue syndrome (CFS), a disabling condition of unknown etiology and with uncertain therapeutic options. Recent advances in elucidating pathophysiology of this disorder revealed hypofunction of the hypothalamic-pituitary-adrenal axis and that fatigue in CFS patients appears to be associated with reduced motor neurotransmission in the central nervous system (CNS) and to a smaller extent with increased fatigability of skeletal muscle. There is also some limited evidence that CFS patients may have excessive serotonergic activity in the brain and low opioid tone.

PRESENTATION OF THE HYPOTHESIS: This work hypothesizes that repeated cold stress may reduce fatigue in CFS because brief exposure to cold may transiently reverse some physiological changes associated with this illness. For example, exposure to cold can activate components of the reticular activating system such as raphe nuclei and locus ceruleus, which can result in activation of behavior and increased capacity of the CNS to recruit motoneurons. Cold stress has also been shown to reduce the level of serotonin in most regions of the brain (except brainstem), which would be consistent with reduced fatigue according to animal models of exercise-related fatigue. Finally, exposure to cold increases metabolic rate and transiently activates the hypothalamic-pituitary-adrenal axis as evidenced by a temporary increase in the plasma levels of adrenocorticotropic hormone, beta-endorphin and a modest increase in cortisol. The increased opioid tone and high metabolic rate could diminish fatigue by reducing muscle pain and accelerating recovery of fatigued muscle, respectively.

TESTING THE HYPOTHESIS: To test the hypothesis, a treatment is proposed that consists of adapted cold showers (20 degrees Celsius, 3 minutes, preceded by a 5-minute gradual adaptation to make the procedure more comfortable) used twice daily.

IMPLICATIONS OF THE HYPOTHESIS: If testing supports the proposed hypothesis, this could advance our understanding of the mechanisms of fatigue in CFS.

 

Source: Shevchuk NA. Possible use of repeated cold stress for reducing fatigue in chronic fatigue syndrome: a hypothesis. Behav Brain Funct. 2007 Oct 24;3:55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2164952/ (Full article)

 

The thoughts and methods for clinical research on acupuncture treatment of chronic fatigue syndrome

Abstract:

The general situation of chronic fatigue syndrome (CFS) and the criteria for its diagnosis are discussed, and it is put forward that making qi and blood of the zang-fu organs balanced is the key to acupuncture treatment of the disease. Such aspects as case selection, point selection and therapeutic assessment are also discussed in the present paper.

 

Source: Yao R. The thoughts and methods for clinical research on acupuncture treatment of chronic fatigue syndrome. J Tradit Chin Med. 2007 Sep;27(3):163-5 http://www.journaltcm.com/modules/Journal/contents/stories/073/1.pdf (Full article)

 

IFN-gamma mediated pathways in patients with fatigue and chronic active Epstein Barr virus-infection

Abstract:

BACKGROUND: Chronic active Epstein Barr virus (EBV)-infection is characterized by mononucleosis like symptoms including fatigue, lymphadenopathy and/or hepatosplenomegaly and serologic evidence for ongoing EBV replication. Interferon-gamma (IFN-gamma) triggers several antiviral mechanisms in target cells including the induction of indoleamine-2,3-dioxygenase (IDO), which degrades the essential amino acid tryptophan to kynurenine. Because tryptophan is a precursor of the neurotransmitter 5-hydroxytryptamine (serotonin), tryptophan depletion by IDO can cause mood disturbances in patients with chronic immune activation.

METHODS: This study investigated the tryptophan metabolism in 20 patients with chronic active EBV-infection, who were followed up for 4 to 8 months and in 10 healthy age-matched controls. The clinical suspicion of chronic active EBV infection was verified by the presence of circulating antibodies against EBV early antigen (EA) and virus capsid antigen (VCA).

RESULTS: Patients with detectable EBV-DNA had higher serum neopterin (p<0.01) and lower tryptophan concentrations (p=0.01) than EBV-DNA negative patients. Serum concentrations of neopterin, indicating Th-1 mediated immune activation via IFN-gamma, were positively correlated to enhanced tryptophan degradation (rs=0.650, p<0.001) in patients, but not in healthy individuals. Patients suffering from more severe symptoms (as assessed by questionnaires) tended to have aggravated tryptophan degradation.

CONCLUSION: Our data show that EBV viremia is associated with cell-mediated immune activation and increased tryptophan degradation, which may partly account for the symptoms found in this disorder.

 

Source: Bellmann-Weiler R, Schroecksnadel K, Holzer C, Larcher C, Fuchs D, Weiss G. IFN-gamma mediated pathways in patients with fatigue and chronic active Epstein Barr virus-infection. J Affect Disord. 2008 May;108(1-2):171-6. Epub 2007 Oct 22. https://www.ncbi.nlm.nih.gov/pubmed/17945348

 

Alexithymia in adolescents with chronic fatigue syndrome

Abstract:

BACKGROUND: Alexithymia is postulated as an important factor in the development of medically unexplained physical symptoms. Chronic fatigue syndrome (CFS) is presently medically unexplained. The aim of this study was to investigate whether the prevalence of alexithymia was higher in adolescents with CFS compared to healthy adolescents. Comorbidity such as anxiety and depression were analyzed as possible confounding factors. Secondly, alexithymia was investigated as a prognostic factor for the recovery of CFS.

METHODS: A cross-sectional study was performed among 40 adolescent outpatients diagnosed with CFS and 36 healthy controls. The 20-item Toronto Alexithymia Scale was used to assess all participants for alexithymia. Additionally, all participants completed a number of questionnaires regarding fatigue (Checklist Individual Strength), somatic complaints (Checklist Somatization Inventory), depression (Children’s Depression Inventory), and trait anxiety (Spielberger State Trait Anxiety Questionnaire). A follow-up study was performed among the CFS adolescents 1 1/2 years after the initial assessment.

RESULTS: CFS adolescents scored higher only on the subscale identifying feelings of the TAS-20 [mean difference after adjustment for depression and anxiety 2.8 (95% CI: 0.6; 4.9]. Twelve CFS adolescents (30%) fulfilled criteria for alexithymia. This subgroup was characterized by higher scores for depression and anxiety and equal scores for fatigue and somatic complaints. At follow-up, no differences in recovery were established between the alexithymic and nonalexithymic CFS adolescents.

CONCLUSIONS: Alexithymia neither appears to be a unique correlate of CFS nor to be a prognostic factor for recovery of the CFS illness.

 

Source: van de Putte EM, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. Alexithymia in adolescents with chronic fatigue syndrome. J Psychosom Res. 2007 Oct;63(4):377-80. https://www.ncbi.nlm.nih.gov/pubmed/17905045

 

Twin analyses of fatigue

Abstract:

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects.

 

Source: Schur E, Afari N, Goldberg J, Buchwald D, Sullivan PF. Twin analyses of fatigue. Twin Res Hum Genet. 2007 Oct;10(5):729-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953372/ (Full article)

 

Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990-1991: results from a two-phase cohort study

Abstract:

BACKGROUND: The aim was to determine the prevalence of chronic fatigue syndrome (CFS), chronic fatigue and fibromyalgia in UK military personnel after the Gulf War 1990-1991.

METHOD: A two-phase cohort study was used. Three randomly selected subsamples identified from a population-based cross-sectional postal survey of over 10,000 current and ex-service UK military personnel (Gulf veterans were those deployed to the Gulf War 1990-1991; non-Gulf veterans were Bosnia peacekeepers 1992-1997 and those on active duty during the Gulf War 1990-1991 but not deployed) were recruited. Their disability status was assessed using the Short Form 36 physical functioning scale; Gulf veterans who reported physical disability (n=111) were compared with non-Gulf (n=133) veterans who reported similar levels of physical disability. Screening for known medical and psychiatric conditions was conducted to exclude medical explanations for disability and symptomatic distress. Standardised criteria for CFS, chronic fatigue and fibromyalgia were used.

RESULTS: Disabled Gulf veterans were more likely to be overweight, have elevated gamma-glutamyl transferase levels and screen positive for hypertension. There were no other clinically significant differences in clinical markers for medically explainable conditions. Disabled Gulf veterans were more likely than similarly disabled Bosnia and Era veterans (adjusted odds ratio 7.8, 95% confidence interval 2.5-24.5) to meet the criteria for CFS. Rates for other medically unexplained conditions were not significantly increased.

CONCLUSIONS: Symptoms in keeping with CFS account for a significant part of the symptomatic distress in Gulf veterans.

Comment in: Chronic fatigue in Gulf War veterans: should it be treated as chronic fatigue syndrome? [Psychol Med. 2009]

 

Source: Ismail K, Kent K, Sherwood R, Hull L, Seed P, David AS, Wessely S. Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990-1991: results from a two-phase cohort study. Psychol Med. 2008 Jul;38(7):953-61. Epub 2007 Sep 25. https://www.ncbi.nlm.nih.gov/pubmed/17892626

 

Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies

Abstract:

BACKGROUND: The aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is still unknown. The identification of risk factors for CFS/ME is of great importance to practitioners.

METHOD: A systematic scoping review was conducted to locate studies that analysed risk factors for CFS/ME using multiple predictors. We searched for published and unpublished literature in 11 electronic databases, reference lists of retrieved articles and guideline stakeholder submissions in conjunction with the development of a forthcoming national UK guideline. Risk factors and findings were extracted in a concise tabular overview and studies synthesized narratively.

RESULTS: Eleven studies were identified that met inclusion criteria: two case-control studies, four cohort studies, three studies combining a cohort with a case-control study design, one case-control and twin study and one cross-sectional survey. The studies looked at a variety of demographic, medical, psychological, social and environmental factors to predict the development of CFS/ME. The existing body of evidence is characterized by factors that were analysed in several studies but without replication of a significant association in more than two studies, and by studies demonstrating significant associations of specific factors that were not assessed in other studies. None of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice.

CONCLUSIONS: Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.

 

Source: Hempel S, Chambers D, Bagnall AM, Forbes C. Risk factors for chronic fatigue syndrome/myalgic encephalomyelitis: a systematic scoping review of multiple predictor studies. Psychol Med. 2008 Jul;38(7):915-26. Epub 2007 Sep 25. https://www.ncbi.nlm.nih.gov/pubmed/17892624

 

Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach

Abstract:

BACKGROUND AND AIMS: The aetiology for chronic fatigue syndrome (CFS) remains elusive although enteroviruses have been implicated as one of the causes by a number of studies. Since most CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1), enterovirus (EV) RNA and culturable virus in the stomach biopsy specimens of patients with CFS was evaluated.

METHODS: 165 consecutive patients with CFS underwent upper GI endoscopies and antrum biopsies. Immunoperoxidase staining was performed using EV-specific monoclonal antibody (mAb) or a control mAb specific for cytomegalovirus (CMV). RT-PCR ELISA was performed on RNA extracted from paraffin sections or samples preserved in RNA later. Biopsies from normal stomach and other gastric diseases served as controls. 75 samples were cultured for EV.

RESULTS: 135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas 7/34 (20%) of the controls stained positive (p< or =0.001). CMV mAb failed to stain any of the biopsy specimens. Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2-8 years later showed positive staining in the paired specimens. EV RNA was detected in 9/24 (37%) paraffin-embedded biopsy samples; 1/21 controls had detectable EV RNA (p<0.01); 1/3 patients had detectable EV RNA from two samples taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic enteroviruses.

CONCLUSION: Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy.

Comment in: Enterovirus infection of the stomach in chronic fatigue syndrome/myalgic encephalomyelitis. [J Clin Pathol. 2008]

 

Source: Chia JK, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008 Jan;61(1):43-8. Epub 2007 Sep 13. https://www.ncbi.nlm.nih.gov/pubmed/17872383

 

NICE behaviour: ME guideline is unworkable

Comment on: Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. [BMJ. 2007]

 

The National Institute for Health and Clinical Excellence (NICE) recommends that everyone with mild or moderate myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) should be offered a course of either cognitive behaviour therapy (CBT) or graded exercise therapy (GET).1

This is despite published evidence remaining weak (especially for group CBT) and inconsistent 2. Patient evidence submitted to the chief medical officer’s report concluded that CBT produced “no change” in 67% of cases and made the condition “worse” in 26% of cases.3 Around 50% of respondents reported that inappropriate exercise therapy had also made their condition “worse.”3

When the NICE estimate on prevalence is used this controversial recommendation will affect some 200 000 people. A one to one course of CBT covering 12 to 16 sessions will cost well over £1500. The cost of a professionally supervised exercise therapy programme is also likely to be substantial.

So where is around £300 million of new money going to come from at a time when very limited funding for some of the newly established NHS clinical services for people with ME/CFS is now being cut?4 And where are all the therapists going to come from? Those already in post often cannot even cope with their current workload.

These are important questions that I raised at a NICE implementation and planning meeting in October 2006—but nobody from NICE could provide a convincing answer. These recommendations are going to be of no value whatsoever to many people with ME/CFS. They are also going to be impossible to implement owing to a lack of both funding and human resources.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976494/

 

Source: Shepherd CB. NICE behaviour: ME guideline is unworkable. BMJ. 2007 Sep 15;335(7619):528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976494/ (Full article)