Low putamen activity associated with poor reward sensitivity in childhood CFS

Posted on 11/14/2016 by wames

Research abstract:

Mizuno K, Kawatani J, Tajima K, Sasaki AT, Yoneda T, Komi M, Hirai T, Tomoda A, Joudoi T, Watanabe Y. Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome. Neuroimage Clin. 2016 Sep 26;12:600-606. eCollection 2016

Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear. The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients.

fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires. Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively.

We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

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Support for the microgenderome invites enquiry into sex differences in ME/CFS

Posted on 11/14/2016 by wames

Research abstract:

The microgenderome defines the interaction between microbiota, sex hormones and the immune system. Our recent research inferred support for the microgenderome by showing sex differences in microbiota-symptom associations in a clinical sample of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

This addendum expands upon the sex-specific pattern of associations that were observed. Interpretations are hypothesised in relation to genera versus species-level analyses and D-lactate theory.

Evidence of sex-differences invites future research to consider sex comparisons in microbial function even when microbial abundance is statistically similar. Pairing assessment of clinical symptoms with microbial culture, DNA sequencing and metabolomics methods will help advance our current understandings of the role of the microbiome in health and disease.

Support for the Microgenderome Invites Enquiry into Sex Differences, by Amy Wallis, Henry Butt, Michelle Ball, Donald P. Lewis & Dorothy Bruck in Gut Microbes, 3 November 2016 [Epub ahead of print]

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Robust evidence of an underlying biological process in ME/CFS

Posted on 11/11/2016 by wames

Miriam Tucker reports on the overwhelming evidence for the biological basis for ME/CFS which was presented at the IACFS/ME conference in the USA in October 2016:

Biomarker Research Advances in ‘Chronic Fatigue Syndrome’, by Miriam E. Tucker in Medscape Medical News, November 08, 2016

Extract:

The symptom heterogeneity, combined with the lack of specific biomarker, has resulted in skepticism among some clinicians that the condition is biologically, rather than psychologically, based.

However, studies during the last decade point to biological underpinnings. At the biennial IACFSME conference, more than 100 papers were presented that contribute further to the evidence base, according to Anthony L. Komaroff, MD, professor of medicine at Harvard University, Boston, Massachusetts, and editor-in-chief of the Harvard Health Letter.

“Case-control studies comparing patients with ME/CFS to both disease comparison groups and healthy control subjects find robust evidence of an underlying biological process involving the brain and autonomic nervous system, immune system, energy metabolism, and oxidative and nitrosative stress,” Dr Komaroff said in a conference summary at the end of the meeting.

He added, “To those people out there who still question whether there is really anything wrong in this illness, my advice to them would be try consulting the evidence.”

Read the full article – you may need to register with Medscape first

Margaret Williams comments on Miriam Tucker’s article:

Professor Hornig told Medscape Medical News: “in addition to accelerating research on causes and treatment, we critically need to find ways to educate medical professionals about the disorder”.

Attempting to educate the UK medical profession, the DWP and benefits decision-makers,
the media and local authorities about ME/CFS has proved impossible for the last 30 years.

Since the psychosocial model is demonstrably wrong, to continue treating ME/CFS as a
behavioural disorder is both unethical and harmful, and is wasteful of tax payers’ money.
Thirty years of behavioural research and interventions have yielded a null result.

The stranglehold of the psychosocial school in the UK over this disorder must be broken so
that actual progress can be made.

How can so much evidence be ignored by so many people for so long?

Read the article: Extracts from Medscape Medical News: “Biomarker Research Advances in ‘Chronic Fatigue Syndrome’ ” by Miriam Tucker, 8th November 2016 – Comment by Margaret Williams 9th November 2016

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Investigation of the effects of vanilloids in animal model of chronic fatigue

Posted on 11/10/2016 by wames

Research abstract:

AIM OF THE STUDY: To assess the effectiveness of TRPV1 modulators in animal model of Chronic fatigue syndrome (CFS). To assess central and peripheral behavioral activity of TRPV1 modulators.

MATERIAL AND METHODS: CFS was induced by forcing the rats to swim for 10min for 21 consecutive days. The rats were treated with capsaicin (TRPV1 agonist, 2.5mg/kg) and n-tert-butylcyclohexanol (TRPV1 antagonist, 10mg/kg) for 21 days 30min before the exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility time, grip strength, locomotor activity, and anxiety level using Rota rod, Actophotometer, and Elevated plus maze model respectively. The other parameters include Plasma corticosterone, adrenal gland and spleen weight, complete blood count, blood urea niterogen (BUN), Lactate dehydrogenase (LDH), Lipid peroxidation, catalase and reduced glutathione (GSH).

RESULTS AND DISCUSSION: TRPV1 modulators reversed (p<0.05) the increase in immobility period, anxiety, spleen weight, BUN and LDH levels, and MDA levels along with decrease in grip strength, locomotor activity, plasma corticosterone, adrenal gland weight, catalase, and GSH. There was also significant increase in total WBC count when compared with the disease control group. The reversal was attributed to modulation of HPA axis, oxidative stress, anaerobic respiration product, muscle degradation product.

CONCLUSION: The present study reveals the effectiveness of n-tert-butylcyclohexanol and capsaicin against chronic fatigue syndrome. The mechanism of action can be attributed to inhibition of TRPV1 channel and thereby modulating pain perception, neuroendocrine function, oxidative stress and immune function.

Investigation of the effects of vanilloids in chronic fatigue syndrome by Kuldeep Sarvaiya, Sunita Goswami in Brain Res Bull. 2016 Sep 28;127:187-194 [Epub ahead of print]

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New Australian genetic marker detection study

Posted on 11/10/2016 by wames

ME Research UK blog post, 6 November 2016: New study – Genetic marker detection

Prof Brett Lidbury and colleagues at the John Curtin School of Medical Research, Australian National University in Canberra are conducting an ongoing programme, funded by charities in Australia, which aims to find biomarkers for ME/CFS using a range of sources – bioinformatics, genetics and pathological testing.

lidbury-group-good

ME Research UK has provided funding to the group to acquire additional genetic data using DNA pooling. It will then be possible to apply machine learning techniques and statistical analyses to an integrated data set combining genetic, clinical and pathological information.

As Prof Lidbury explained in a recent interview,

“We’re looking for patterns in the data which can help with biomarker pattern detection and provide clues to disease mechanisms. With complex diseases like this, we need to look at many factors simultaneously, and cross-disciplinary studies are necessary to integrate the findings from different avenues of research investigation.”

Read more at MER UK’s specific project page, Two dimensional sequencing and machine learning to maximise genetic marker detection

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Hypothalamic-Pituitary-Adrenal Hypofunction in ME/CFS

Posted on 11/09/2016 by wames

Review abstract:

There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels.

This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity. Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS.

Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS. Mechanistic explanations comprise increased levels of tumor necrosis factor-?, T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-?, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms. HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.

Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways by Gerwyn Morris, George Anderson, Michael Maes in Mol Neurobiol. 2016 Oct 20. [Epub ahead of print]

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Studies on CBT & GET for ME/CFS are misleading, says Swedish prof

Posted on 11/09/2016 by wames

Article abstract:

There have been a number of studies on Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS based on a treatment model where the disease is perpetuated by cognitive processes. Although the studies are flawed and the model lacks scientific support, the treatments are described as evidence based.

The studies are non-blinded and rely on subjective outcomes. There are no objective measures of adherence. The diagnostic criteria vary, and the participating patients often have one or several psychiatric diagnoses apart from suffering from chronic fatigue. The underlying model has no theoretical foundation and is at odds with physiological findings. Surveys suggest that the efficacy of CBT is no better than placebo and that GET is harmful. Therefore, cognitive behavioral therapy and graded exercise therapy for ME/CFS are not evidence based.

More info:

This is a translation of an article published in Socialmedicinsk tidskrift, Stockholm, Sweden,by Assoc. Prof of Physics & Member of the Swedish ME Association, Sten Helmfrid  on September 28th, 2016. http://socialmedicinsktidskrift.se

Download the article in English: Studies on Cognitive Behavioral Therapy and Graded Exercise Therapy for ME/CFS are misleading

Link to the original article in Swedish (vol. 93, issue 4, pp. 433 -44): http://socialmedicinsktidskrift.se/index.php/smt/article/view/1450/1255

Citation: Helmfrid S. Studier av kognitiv beteendeterapi och gradvis ökad träning vid ME/CFS är missvisande. Soc Med Tidskr. 2016;93(4):433–44.

 

 

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Dr Keith Geraghty requests experiences of CBT & GET

Posted on 11/08/2016 by wames

Dr Keith Geraghty, researcher at the University of Manchester (@keithgeraghty) has tweeted at 6:09 p.m. on Mon, Nov 07, 2016:

Ever experience adverse reactions to CBT or GET in CFS treatment – email me @ Keith.geraghty@manchester.ac.uk – we want to hear your story.

About Keith:

Keith Geraghty is an Honorary Research Fellow within the Primary Care Section of the Institute of Population Health. His role is to support current grant applications and research projects and to conduct independent work in the area of public health, health services research and primary care.

Keith has a special interest in medically unexplained symptoms, patient safety issues, doctor patient relations, and Chronic Fatigue Syndrome/ME.

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Activity patterns in response to symptoms in patients being treated for CFS

Posted on 11/07/2016 by wames

Research abstract:

Objective:
Cognitive-behavioral models of chronic fatigue syndrome (CFS) propose that patients respond to symptoms with 2 predominant activity patterns-activity limitation and all-or-nothing behaviors-both of which may contribute to illness persistence. The current study investigated whether activity patterns occurred at the same time as, or followed on from, patient symptom experience and affect.

Method
Twenty-three adults with CFS were recruited from U.K. CFS services. Experience sampling methodology (ESM) was used to assess fluctuations in patient symptom experience, affect, and activity management patterns over 10 assessments per day for a total of 6 days.

Assessments were conducted within patients’ daily life and were delivered through an app on touchscreen Android mobile phones. Multilevel model analyses were conducted to examine the role of self-reported patient fatigue, pain, and affect as predictors of change in activity patterns at the same and subsequent assessment.

Results
Current experience of fatigue-related symptoms and pain predicted higher patient activity limitation at the current and subsequent assessments whereas subjective wellness predicted higher all-or-nothing behavior at both times. Current pain predicted less all-or-nothing behavior at the subsequent assessment.

In contrast to hypotheses, current positive affect was predictive of current activity limitation whereas current negative affect was predictive of current all-or-nothing  behavior. Both activity patterns varied at the momentary level.

Conclusions
Patient symptom experiences appear to be driving patient activity management patterns in line with the cognitive-behavioral model of CFS. ESM offers a useful method for examining multiple interacting variables within the context of patients’ daily life.

Activity patterns in response to symptoms in patients being treated for Chronic Fatigue Syndrome: An experience sampling methodology study by Band R, Barrowclough C, Caldwell K, Emsley R, Wearden A. in Health Psychology, 7 Nov 2016 [Preprint]

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Postexertion ‘crash,’ not fatigue per se, marks CFS

Posted on 11/07/2016 by wames

Medscape Medical News article, by Miriam Tucker, November 04, 2016: Post exertion ‘Crash,’ not Fatigue per se, Marks Syndrome

Article extract:

The name “chronic fatigue syndrome” is being phased out not just because it is viewed as trivializing a condition that renders many patients completely or nearly bedbound but also because it gives the misleading impression that the illness is characterized simply by prolonged unexplained fatigue.

In fact, ME/CFS is characterized by multiple heterogeneous symptoms, with PEM, often described as a “crash” or a significant worsening of already-present symptoms, being a near-universal experience.

“Many studies show that physical exertion can help with insomnia in healthy people, and even people with other medical conditions such as depression, anxiety, or even heart failure. But in ME/CFS patients, physical exertion exacerbates their symptoms,” conference cochair Lily Chu, MD, from Stanford University, Palo Alto, California, told Medscape Medical News.

“The way these patients present is very different from healthy people or people with other medical conditions.”

Indeed, recent diagnostic criteria for the illness, including the February 2015 Institute of Medicine report, require PEM among other symptoms to make the diagnosis of ME or ME/CFS as opposed to older definitions of CFS. However, the Centers for Disease Control and Prevention continues to endorse a 1994 CFS definition that lists PEM as an optional criterion, but does not make it mandatory for the diagnosis.

What Is PEM?

At the IACFSME conference, Dr Chu presented findings from her group’s study of 150 patients diagnosed with the 1994 criteria who completed a survey about their symptoms after physical or cognitive exertion or emotional distress.

The majority (89%) reported experiencing PEM after both types of triggers, but 10% reported no effect after emotional distress, whereas overall physical exertion elicited significantly more symptoms than did emotional distress (seven vs five; P < .001).

Although fatigue was the most commonly exacerbated symptom, more than 30% of patients also reported cognitive difficulties, sleep disturbance, headache, muscle pain, and influenza-like feelings. Some also reported gastrointestinal, orthostatic, and mood-related exacerbations.

Timing and duration of symptoms varied among respondents and per respondent, but 11% reported a consistent post trigger delay of at least 24 hours, whereas 23% said that their symptoms typically lasted for 3 or more days.

 “PEM consists of more than just fatigue and pain. It’s an exacerbation of multiple symptoms, some of which are atypically associated with exertion,” Dr Chu told Medscape Medical News.

She added, “PEM can be difficult for clinicians and patients to identify. We suggest patients keep a diary for a week or two, documenting symptoms and activity so we can look at and see relationship of activity and timing, duration, and intensity of symptoms.”

Read full article, including overview of other biological studies into PEM [you will need to register with Medscape]

 

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