Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype

Abstract:

Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS).

All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years). Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI).

Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype.

Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.

 

Source: Meyer B, Nguyen CB, Moen A, Fagermoen E, Sulheim D, Nilsen H, Wyller VB, Gjerstad J. Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype. PLoS One. 2015 Oct 16;10(10):e0140883. doi: 10.1371/journal.pone.0140883. ECollection 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608737/ (Full article)

 

Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia

Abstract:

PURPOSE: The purpose of this study was to conduct a longitudinal examination of cognitive complaints and functional status in patients with chronic fatigue syndrome (CFS) alone and those who also had fibromyalgia (CFS/FM).

METHODS: A total of 93 patients from a tertiary care fatigue clinic were evaluated on four occasions, each 6 months apart. Each evaluation included a tender point assessment, and self-reported functional status and cognitive complaints.

RESULTS: Patients with CFS/FM reported significantly worse physical functioning, more bodily pain, and more cognitive difficulties (visuo-perceptual ability and verbal memory) than patients with CFS alone. Over time, bodily pain decreased only for participants with CFS alone. Verbal memory problems were associated with more bodily pain for both patient groups, whereas visuo-perceptual problems were associated with worse functional status for patients with CFS alone.

CONCLUSIONS: This study adds to the literature on functional status, longitudinal course, and cognitive difficulties among patients with CFS and those with CFS and FM. The results suggest that patients with CFS/FM are more disabled, have more cognitive complaints, and improve more slowly over time than patients with CFS alone. Specific cognitive difficulties are related to worse functional status, which supports the addition of cognitive difficulties to the FM case criteria.

 

Source: Schmaling KB, Betterton KL. Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia. Qual Life Res. 2016 May;25(5):1257-63. doi: 10.1007/s11136-015-1160-y. Epub 2015 Oct 15. https://www.ncbi.nlm.nih.gov/pubmed/26471263

 

The Cognitive Behavioral Treatment of Depression and Low Self-Esteem in the Context of Pediatric Chronic Fatigue Syndrome (CFS/ME): A Case Study

Abstract:

PROBLEM: Up to one in three young people with chronic fatigue syndrome (CFS/ME) also has depressive symptoms. It is not known how best to treat young people with this comorbidity.

METHOD: This case report seeks to describe and discuss the use of a cognitive behavioral approach for depression and low self-esteem in a 16-year-old girl with CFS/ME.

FINDINGS/CONCLUSION: Therapy was effective in remediating the young person’s mood difficulties, but appeared to exacerbate their CFS/ME symptoms. Therefore, it is crucial that CFS/ME and mood treatments are designed and trialed to ensure a complementary approach. Good communication and joint working between involved professionals is also important, and ideally, treatments for mood and for CFS/ME would be provided by the same team to facilitate this.

© 2015 Wiley Periodicals, Inc.

 

Source: Loades M. The Cognitive Behavioral Treatment of Depression and Low Self-Esteem in the Context of Pediatric Chronic Fatigue Syndrome (CFS/ME): A Case Study. J Child Adolesc Psychiatr Nurs. 2015 Nov;28(4):165-74. doi: 10.1111/jcap.12125. Epub 2015 Oct 16. https://www.ncbi.nlm.nih.gov/pubmed/26470755

 

A new case definition of Neuro-Inflammatory and Oxidative Fatigue (NIOF), a neuroprogressive disorder, formerly known as chronic fatigue syndrome or Myalgic Encephalomyelitis: results of multivariate pattern recognition methods and external validation by neuro-immune biomarkers

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) or Myalgic Encephalomyelitis (ME) is characterized by neuro-psychiatric (e.g. depression, irritability, sleep disorders, autonomic symptoms and neurocognitive defects) and physio-somatic (fatigue, a flu-like malaise, hyperalgesia, irritable bowel, muscle pain and tension) symptoms. New ME/CFS case definitions based on consensus criteria among experts are largely inadequate, e.g. those of the US Institute of Medicine .

OBJECTIVES: The aim of the present study was to delineate a new case definition of ME/CFS based on pattern recognition methods and using neuro-immune, inflammatory, oxidative and nitrosative stress (neuro-IO&NS) biomarkers as external validating criteria.

METHODS: We measured the 12-item Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale in 196 subjects with CFS (CDC criteria) and 83 with chronic fatigue. The “Neuro-IO&NS” biomarkers were: IgM / IgA responses against LPS of gut commensal bacteria (leaky gut), IgM responses to O&NS modified neoepitopes, autoimmunity to serotonin, plasma interleukin-1 (IL-1) and serum neopterin.

RESULTS: Cluster analysis showed the presence of two well-separated clusters with highly significant differences in symptoms and biomarkers. The cluster with higher scores on all FF items was externally validated against all IO&NS biomarkers and therefore this diagnostic group was labeled “Neuro-IO&NS Fatigue” or “Neuro-Inflammatory and Oxidative Fatigue” (NIOF). An algorithm was constructed which defined NIOF as chronic fatigue and 4 or more of the following 6 symptoms: muscle tension, memory disturbances, sleep disorders, irritable bowel, headache or a flu-like malaise. There was a significant overlap between NIOF and CFS although NIOF criteria were much more restrictive. Factor analysis showed two factors, the first a fatigue-hyperalgesia (fibromyalgic complaints) and the second a fatigue-depression factor.

 

Source: Maes M. A new case definition of Neuro-Inflammatory and Oxidative Fatigue (NIOF), a neuroprogressive disorder, formerly known as chronic fatigue syndrome or Myalgic Encephalomyelitis: results of multivariate pattern recognition methods and external validation by neuro-immune biomarkers. Neuro Endocrinol Lett. 2015;36(4):320-9. https://www.ncbi.nlm.nih.gov/pubmed/26454487

 

What matters to children with CFS/ME? A conceptual model as the first stage in developing a PROM

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is relatively common and disabling. Research is hampered because current patient-reported outcome measures (PROMs) do not capture outcomes that are important to children with CFS/ME.

AIM: The aim of this study was to explore the aspects of life and health outcomes that matter to children with CFS/ME.

METHODS: Twenty-five children with CFS/ME were interviewed (11 males, 14 females; mean age 12.9 years (SD 2.2), range 8-17). Twelve were trial participants interviewed during the trial and 13 were recruited as part of a follow-up qualitative study. Parents were present in 19 interviews with their children. Three mothers participated in a focus group. All the interviews and the focus group were audio-recorded and transcribed. Data were analysed thematically using techniques of constant comparison. NVivo was used to structure and categorise data in a systematic way.

RESULTS: Children identified four key themes (health outcome domains): ‘symptoms’ that fluctuated, which caused an unpredictable reduction in both ‘physical activity’ and ‘social participation’ all of which impacted on ’emotional well-being’. These domains were influenced by both ‘management’ and ‘contextual factors’, which could be positive and negative. The relationship between healthcare and school was considered pivotal.

CONCLUSIONS: Children’s descriptions helped to inform a conceptual model that is necessary to develop a new paediatric CFS/ME PROM. Doctors need to be aware of how children conceptualise CFS/ME; the relationship between healthcare and school is fundamental to ameliorate the impact of CFS/ME.

TRIAL REGISTRATION NUMBER: ISRCTN81456207.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

 

Source: Parslow R, Patel A, Beasant L, Haywood K, Johnson D, Crawley E. What matters to children with CFS/ME? A conceptual model as the first stage in developing a PROM. Arch Dis Child. 2015 Dec;100(12):1141-7. doi: 10.1136/archdischild-2015-308831. Epub 2015 Oct 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680202/ (Full article)

 

Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses

Abstract:

Although altered resting-state functional connectivity (FC) is a characteristic of many chronic pain conditions, it has not yet been evaluated in patients with chronic fatigue. Our objective was to investigate the association between fatigue and altered resting-state FC in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Thirty-six female subjects, 19 ME/CFS and 17 healthy controls, completed a fatigue inventory before undergoing functional magnetic resonance imaging. Two methods, (1) data driven and (2) model based, were used to estimate and compare the intraregional FC between both groups during the resting state (RS).

The first approach using independent component analysis was applied to investigate five RS networks: the default mode network, salience network (SN), left frontoparietal networks (LFPN) and right frontoparietal networks, and the sensory motor network (SMN).

The second approach used a priori selected seed regions demonstrating abnormal regional cerebral blood flow (rCBF) in ME/CFS patients at rest. In ME/CFS patients, Method-1 identified decreased intrinsic connectivity among regions within the LFPN. Furthermore, the FC of the left anterior midcingulate with the SMN and the connectivity of the left posterior cingulate cortex with the SN were significantly decreased.

For Method-2, five distinct clusters within the right parahippocampus and occipital lobes, demonstrating significant rCBF reductions in ME/CFS patients, were used as seeds. The parahippocampal seed and three occipital lobe seeds showed altered FC with other brain regions. The degree of abnormal connectivity correlated with the level of self-reported fatigue.

Our results confirm altered RS FC in patients with ME/CFS, which was significantly correlated with the severity of their chronic fatigue.

 

Source: Gay CW, Robinson ME, Lai S, O’Shea A, Craggs JG, Price DD, Staud R. Abnormal Resting-State Functional Connectivity in Patients with Chronic Fatigue Syndrome: Results of Seed and Data-Driven Analyses. Brain Connect. 2016 Feb;6(1):48-56. doi: 10.1089/brain.2015.0366. Epub 2015 Nov 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744887/ (Full article)

 

Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter

Abstract:

BACKGROUND: In addition to the frequently reported pain complaints, performance-based cognitive capabilities in patients with chronic fatigue syndrome (CFS) with and without comorbid fibromyalgia (FM) are significantly worse than those of healthy controls. In various chronic pain populations, cognitive impairments are known to be related to pain severity. However, to the best of our knowledge, the association between cognitive performance and experimental pain measurements has never been examined in CFS patients.

OBJECTIVES: This study aimed to examine the association between cognitive performance and self-reported as well as experimental pain measurements in CFS patients with and without FM.

STUDY DESIGN: Observational study.

SETTING: The present study took place at the Vrije Universiteit Brussel and the University of Antwerp.

METHODS: Forty-eight (18 CFS-only and 30 CFS+FM) patients and 30 healthy controls were studied. Participants first completed 3 performance-based cognitive tests designed to assess selective and sustained attention, cognitive inhibition, and working memory capacity. Seven days later, experimental pain measurements (pressure pain thresholds [PPT], temporal summation [TS], and conditioned pain modulation [CPM]) took place and participants were asked to fill out 3 questionnaires to assess self-reported pain, fatigue, and depressive symptoms.

RESULTS: In the CFS+FM group, the capacity of pain inhibition was significantly associated with cognitive inhibition. Self-reported pain was significantly associated with simple reaction time in CFS-only patients. The CFS+FM but not the CFS-only group showed a significantly lower PPT and enhanced TS compared with controls.

LIMITATIONS: The cross-sectional nature of this study does not allow for inferences of causation.

CONCLUSIONS: The results underline disease heterogeneity in CFS by indicating that a measure of endogenous pain inhibition might be a significant predictor of cognitive functioning in CFS patients with FM, while self-reported pain appears more appropriate to predict cognitive functioning in CFS patients without FM.

 

Source: Ickmans K, Meeus M, De Kooning M, Lambrecht L, Pattyn N, Nijs J. Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter. Pain Physician. 2015 Sep-Oct;18(5):E841-52. http://www.painphysicianjournal.com/current/pdf?article=MjQxOA%3D%3D&journal=91 (Full article as PDF file)

 

Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a severe disease characterized by various symptoms of immune dysfunction. CFS onset is typically with an infection and many patients suffer from frequently recurrent viral or bacterial infections. Immunoglobulin and mannose binding lectin (MBL) deficiency are frequent causes for increased susceptibility to infections.

In this study we retrospectively analysed 300 patients with CFS for immunoglobulin and MBL levels, and B-cell subset frequencies. 25% of the CFS patients had decreased serum levels of at least one antibody class or subclass with IgG3 and IgG4 subclass deficiencies as most common phenotypes.

However, we found elevated immunoglobulin levels with an excess of IgM and IgG2 in particular in another 25% of patients. No major alteration in numbers of B cells and B-cell subsets was seen. Deficiency of MBL was found in 15% of the CFS patients in contrast to 6% in a historical control group. In a 2nd cohort of 168 patients similar frequencies of IgG subclass and MBL deficiency were found. Thus, humoral immune defects are frequent in CFS patients and are associated with infections of the respiratory tract.

Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

 

Source: Guenther S, Loebel M, Mooslechner AA, Knops M, Hanitsch LG, Grabowski P, Wittke K, Meisel C, Unterwalder N, Volk HD, Scheibenbogen C. Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome. Hum Immunol. 2015 Oct;76(10):729-35. doi: 10.1016/j.humimm.2015.09.028. Epub 2015 Sep 30. https://www.ncbi.nlm.nih.gov/pubmed/26429318

 

Myalgic Encephalomyelitis: Symptoms and Biomarkers

Abstract:

Myalgic Encephalomyelitis (ME) continues to cause significant morbidity worldwide with an estimated one million cases in the United States. Hurdles to establishing consensus to achieve accurate evaluation of patients with ME continue, fueled by poor agreement about case definitions, slow progress in development of standardized diagnostic approaches, and issues surrounding research priorities. Because there are other medical problems, such as early MS and Parkinson’s Disease, which have some similar clinical presentations, it is critical to accurately diagnose ME to make a differential diagnosis.

In this article, we explore and summarize advances in the physiological and neurological approaches to understanding, diagnosing, and treating ME. We identify key areas and approaches to elucidate the core and secondary symptom clusters in ME so as to provide some practical suggestions in evaluation of ME for clinicians and researchers.

This review, therefore, represents a synthesis of key discussions in the literature, and has important implications for a better understanding of ME, its biological markers, and diagnostic criteria. There is a clear need for more longitudinal studies in this area with larger data sets, which correct for multiple testing.

 

Source: Jason LA, Zinn ML, Zinn MA. Myalgic Encephalomyelitis: Symptoms and Biomarkers. Curr Neuropharmacol. 2015;13(5):701-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/ (Full article)

 

Randomised controlled trial of cognitive behaviour therapy delivered in groups of patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Meta-analyses have been inconclusive about the efficacy of cognitive behaviour therapies (CBTs) delivered in groups of patients with chronic fatigue syndrome (CFS) due to a lack of adequate studies.

METHODS: We conducted a pragmatic randomised controlled trial with 204 adult CFS patients from our routine clinical practice who were willing to receive group therapy. Patients were equally allocated to therapy groups of 8 patients and 2 therapists, 4 patients and 1 therapist or a waiting list control condition. Primary analysis was based on the intention-to-treat principle and compared the intervention group (n = 136) with the waiting list condition (n = 68). The study was open label.

RESULTS: Thirty-four (17%) patients were lost to follow-up during the course of the trial. Missing data were imputed using mean proportions of improvement based on the outcome scores of similar patients with a second assessment. Large and significant improvement in favour of the intervention group was found on fatigue severity (effect size = 1.1) and overall impairment (effect size = 0.9) at the second assessment. Physical functioning and psychological distress improved moderately (effect size = 0.5). Treatment effects remained significant in sensitivity and per-protocol analyses. Subgroup analysis revealed that the effects of the intervention also remained significant when both group sizes (i.e. 4 and 8 patients) were compared separately with the waiting list condition.

CONCLUSIONS: CBT can be effectively delivered in groups of CFS patients. Group size does not seem to affect the general efficacy of the intervention which is of importance for settings in which large treatment groups are not feasible due to limited referral.

© 2015 S. Karger AG, Basel.

 

Source: Wiborg JF, van Bussel J, van Dijk A, Bleijenberg G, Knoop H. Randomised controlled trial of cognitive behaviour therapy delivered in groups of patients with chronic fatigue syndrome. Psychother Psychosom. 2015;84(6):368-76. doi: 10.1159/000438867. Epub 2015 Sep 25. https://www.ncbi.nlm.nih.gov/pubmed/26402868

 

Comment

Tom Kindlon 2015 Oct 06 4:36 p.m.

No objective outcome measures were used

This trial just used subjective outcome measures. Objective outcome measures are important as subjective outcome measures may not translate into objective improvements with graded activity-oriented interventions in Chronic Fatigue Syndrome (CFS) (1-3). Examples of more objective outcome measures that have been used in CFS interventional studies include actigraphy, employment data, disability payments data and exercise testing.

References:

1 Kewley AJ. Does Cognitive Behavioral Therapy or Graded Exercise Therapy Reduce Disability in Chronic Fatigue Syndrome Patients? Objective Measures Are Necessary. Clinical Psychology: Science and Practice 2013:20;321-322.

2 Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G. How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity. Psychol Med. 2010:40;1281-7.

3 Kindlon T. Comment on: Exercise therapy for chronic fatigue syndrome. http://www.ncbi.nlm.nih.gov/pubmed/25674924#cm25674924_11779