TGI Friday! Our weekly round-up of recently published research abstracts | 26 May 2017

May 26, 2017

From The British Journal of Psychiatry, 2 May 2017.

Controversy over exercise therapy for chronic fatigue syndrome: key lessons for clinicians and academics

Alex J Mitchell
Professor of Psycho-Oncology and Liaison Psychiatry at the University of Leicester.


Chronic fatigue syndrome (CFS) is syndrome of unremitting fatigue of at least 6 months’ duration that causes significant disability. Exercise therapy has a proven track record in medicine and could be effective for some patients with CFS. An updated Cochrane review of eight studies appeared to suggest that exercise helps fatigue symptoms, but with only a small probability of recovery and/or improvement in daily function. Provisional data on acceptability suggest that most patients are willing to participate. However, one key study (PACE), which was well powered and influential in the Cochrane review, has been met with considerable controversy owing to lack of clarity on outcomes. Following release of the PACE study primary data, re-analysis suggested smaller effect sizes than initially reported.

MEA editorial note: The Cochrane Review that Professor Mitchell refers to can be found here:

From the Journal of Translational Medicine (open access), 11 May 2017.

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival

Chinh Bkrong Nguyen (1,2), Lene Alsøe(3), Jessica M. Lindvall(4), Dag Sulheim(5), Even Fagermoen(6), Anette Winger(7), Mari Kaarbø(8), Hilde Nilsen(3) and Vegard Bruun Wyller (1,10).
1. Department of Paediatrics and Adolescent Health, Akershus University Hospital
2. Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo
3. Institute of Clinical Medicine, Department of Clinical Molecular Biology, University of Oslo, and Akershus University Hospital
4. National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University
5. Department of Paediatrics, Lillehammer County Hospital
6. Department of Anesthesiology and Critical Care, Oslo University Hospital
7. Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences
8. Department of Microbiology, Oslo University Hospital
9. Department of Paediatrics and Adolescent Health, Akershus University Hospital
10. Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo



Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group.


CFS patients (12–18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings.


A total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated.


Adolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise.

Trial registration Clinical Trials NCT01040429

From BMJ Open, 16 May 2017.

Medical education and training

Randomised controlled trial of online continuing education for health professionals to improve the management of chronic fatigue syndrome: a study protocol

Sophie H Li(1,2), Carolina X Sandler(1,3), Sally M Casson(1), Joanne Cassar(1,3), Tina Bogg(1), Andrew R Lloyd(3), Benjamin K Barry(1,4,5).

1. School of Medical Sciences, University of New South Wales, Sydney, Australia
2. School of Psychology, The University of New South Wales, Sydney, Australia
3. The Kirby Institute, University of New South Wales, Sydney, Australia
4. Neuroscience Research Australia, University of New South Wales, Sydney, Australia
5. School of Clinical Medicine, University of Queensland, Brisbane, Australia
Correspondence to Dr. Benjamin K Barry;



Chronic fatigue syndrome (CFS) is a serious and debilitating illness that affects between 0.2%–2.6% of the world’s population. Although there is level 1 evidence of the benefit of cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for some people with CFS, uptake of these interventions is low or at best untimely. This can be partly attributed to poor clinician awareness and knowledge of CFS and related CBT and GET interventions. This trial aims to evaluate the effect of participation in an online education programme, compared with a wait-list control group, on allied health professionals’ knowledge about evidence-based CFS interventions and their levels of confidence to engage in the dissemination of these interventions.


A randomised controlled trial consisting of 180 consenting allied health professionals will be conducted. Participants will be randomised into an intervention group (n=90) that will receive access to the online education programme, or a wait-list control group (n=90). The primary outcomes will be: 1) knowledge and clinical reasoning skills regarding CFS and its management, measured at baseline, post-intervention and follow-up, and 2) self-reported confidence in knowledge and clinical reasoning skills related to CFS. Secondary outcomes include retention of knowledge and satisfaction with the online education programme. The influence of the education programme on clinical practice behaviour, and self-reported success in the management of people with CFS, will also be assessed in a cohort study design with participants from the intervention and control groups combined.


The study protocol has been approved by the Human Research Ethics Committee at The University of New South Wales (approval number HC16419). Results will be disseminated via peer-reviewed journal articles and presentations at scientific conferences and meetings.

Trial registration ACTRN12616000296437.

From the Journal of Health Psychology, 17 May 2017

Distress signals: Does cognitive behavioural therapy reduce or increase distress in chronic fatigue syndrome/myalgic encephalomyelitis?

Keith R Laws


Reducing the psychological distress associated with chronic fatigue syndrome/myalgic encephalomyelitis is seen as a key aim of cognitive
behavioural therapy. Although cognitive behavioural therapy is promoted precisely in this manner by the National Institute of Clinical Excellence, the evidence base on distress reduction from randomised controlled trials is limited, equivocal and poor quality.

Crucially, data derived from multiple patient surveys point to worsening and increase distress; however, despite being invited, such data have been dismissed as second class by National Institute of Clinical Excellence. Crucially, the claim by National Institute of Clinical Excellence that cognitive behavioural therapy reduces distress in chronic fatigue syndrome/myalgic encephalomyelitis is not only at odds with what patients repeatedly report in surveys, but with their own gold-standard randomised controlled trial and meta-analytic data.

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