Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance?

Abstract:

OBJECTIVE: A subgroup of patients with Chronic Fatigue Syndrome (CFS) has cognitive impairments, reflected by deviant neuropsychological test performance. However, abnormal test scores can also be caused by suboptimal effort. We hypothesized that worse neuropsychological test performance and underperformance were related to each other and to a smaller reduction in fatigue, functional impairments, physical limitations and higher dropout rates following cognitive behavior therapy (CBT) for CFS.

METHODS: Data were drawn from a previous trial, in which CFS patients were randomized to two conditions; 1) guided self-instruction and additional CBT (n=84) or 2) waiting period followed by regular CBT for CFS (n=85). Underperformance was assessed using the Amsterdam Short Term Memory Test (<84). To test neuropsychological test performance, the Symbol Digit Modalities Task, a simple reaction time task and a choice reaction time task were used. Interaction effects were determined between underperformance and neuropsychological test performance on therapy outcomes.

RESULTS: Underperformance was associated to worse neuropsychological test performance, but there were no significant interaction effects of these two factors by therapy on fatigue severity, functional impairments and physical limitations, but there was a significant main effect of underperformance on functional impairments, physical limitations and dropout rates.

CONCLUSION: Underperformance or neuropsychological test performance was not related to the change in fatigue, functional impairments, and physical limitations following CBT for CFS. However, underperforming patients did drop out more often. Therapists should pay attention to beliefs and behavioral or environmental factors that might maintain underperformance and increase the risk of dropout.

© 2013

Comment in

Source: Goedendorp MM, van der Werf SP, Bleijenberg G, Tummers M, Knoop H. Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance? J Psychosom Res. 2013 Sep;75(3):242-8. doi: 10.1016/j.jpsychores.2013.07.011. Epub 2013 Jul 26. https://www.ncbi.nlm.nih.gov/pubmed/23972413

 

The process of cognitive behaviour therapy for chronic fatigue syndrome: which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue?

Abstract:

OBJECTIVE: Cognitive behaviour therapy (CBT) can significantly reduce fatigue in chronic fatigue syndrome (CFS), but little is known about the process of change taking place during CBT. Based on a recent treatment model (Wiborg et al. J Psych Res 2012), we examined how (changes in) cognitions and behaviour are related to the decrease in fatigue.

METHODS: We included 183 patients meeting the US Centers for Disease Control criteria for CFS, aged 18 to 65 years, starting CBT. We measured fatigue and possible process variables before treatment; after 6, 12 and 18 weeks; and after treatment. Possible process variables were sense of control over fatigue, focusing on symptoms, self-reported physical functioning, perceived physical activity and objective (actigraphic) physical activity. We built multiple regression models, explaining levels of fatigue during therapy by (changes in) proposed process variables.

RESULTS: We observed large individual variation in the patterns of change in fatigue and process variables during CBT for CFS. Increases in the sense of control over fatigue, perceived activity and self-reported physical functioning, and decreases in focusing on symptoms explained 20 to 46% of the variance in fatigue. An increase in objective activity was not a process variable.

CONCLUSION: A change in cognitive factors seems to be related to the decrease in fatigue during CBT for CFS. The pattern of change varies considerably between patients, but changes in process variables and fatigue occur mostly in the same period.

© 2013

 

Source: Heins MJ, Knoop H, Burk WJ, Bleijenberg G. The process of cognitive behaviour therapy for chronic fatigue syndrome: which changes in perpetuating cognitions and behaviour are related to a reduction in fatigue? J Psychosom Res. 2013 Sep;75(3):235-41. doi: 10.1016/j.jpsychores.2013.06.034. Epub 2013 Jul 19. http://www.jpsychores.com/article/S0022-3999(13)00266-3/fulltext (Full article)

 

Response to Derek Enlander

Sir,

Derek Enlander’s comments refer to Table 4 in our paper1 which describes the association of baseline characteristics with change in physical function at follow-up. It does not describe the outcome which can be found in Table 2. This shows an improvement in fatigue (−6.8; 95% CI −7.4 to −6.2; P < 0.001), physical function (4.4, 95% CI 3.0 to 5.8; P < 0.001), anxiety, depression and pain at follow-up.

In addition, as we state in the methods, the scores from the different inventories were re-scaled, so that a regression coefficient of 1 represents a 10% change in the score. Hence, the coefficient of −0.47 (95% CI −0.58 to −0.36) for the mean change in (re-scaled) SF-36 physical function per unit (re-scaled) Chalder Fatigue score at baseline, indicates that each 10% increment in baseline Chalder Fatigue (i.e. 3.3 points on the original 0 to 33 scale) is associated with a mean change of −4.7 points (95% CI −5.8 to −3.6 points) on the original 0 to 100 SF-36 scale at follow-up. Similarly, the coefficient of 0.81 (95% CI 0.75 to 0.87) for the mean change in (re-scaled) SF-36 physical function per unit (re-scaled) SF-36 score at baseline, indicates that each 10% increment in baseline physical function (i.e. 10 points on the original 0 to 100 SF-36 scale) is associated with a mean change of 8.1 points (95% CI 7.5 to 8.7 points) on the original 0 to 100 SF-36 scale at follow-up.

In summary, our paper shows that patients showed improvements in fatigue, physical disability, anxiety, depression and pain. Table 4 referred to by Derek Enlander show that worse fatigue and disability at assessment predict a worse outcome for disability at follow-up.

You can read the rest of this comment here: https://academic.oup.com/qjmed/article/107/3/247/1569245/Response-to-Derek-Enlander

Comment on

 

Source: Crawley E. Response to Derek Enlander. QJM. 2014 Mar;107(3):247. doi: 10.1093/qjmed/hct171. Epub 2013 Aug 22. https://academic.oup.com/qjmed/article/107/3/247/1569245/Response-to-Derek-Enlander (Full article)

 

 

RE: ‘Treatment outcome in adults with chronic fatigue syndrome: a prospective study

Sir,

In a very impressive paper1 embracing a large cohort (834) of ME CFS (myalgic encephalomyelitis, Chronic fatigue syndrome) patients selected by the Fukuda criteria, we can see in Table 4 the associations and changes of baseline characteristics with physical function at follow-up in the Chalder Fatigue scale −0.47 (−0.58 to −0.36) and in the SF-36 (physical function phase) 0.81 (0.75 to 0.87). This perhaps represents approximately an 8% change after the PACE recommended GET/CBT therapy after a variable number of months of therapy. This shows a relatively insignificant improvement. Do we presume that the authors therefore are not emphatically encouraging the PACE recommendation of GET/CBT as a means of primary treatment of ME CFS?

Comment in

Comment on

Source: Enlander D. RE: ‘Treatment outcome in adults with chronic fatigue syndrome: a prospective study. QJM. 2014 Jan;107(1):87. doi: 10.1093/qjmed/hct169. Epub 2013 Aug 22. https://academic.oup.com/qjmed/article/107/1/87/1513843/RE-Treatment-outcome-in-adults-with-chronic

 

Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial

Abstract:

BACKGROUND: Pain is a common symptom of chronic fatigue syndrome (CFS). We investigated the effects of the treatments used in the PACE trial [cognitive behavioural therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy (APT) and specialist medical care (SMC)] on pain in CFS.

METHOD: We compared pain outcomes including individual painful symptoms, taken from the CDC criteria for CFS and co-morbid fibromyalgia. We modelled outcomes adjusting for baseline variables with multiple linear regression.

RESULTS: Significantly less frequent muscle pain was reported by patients following treatment with CBT compared to SMC (mean difference = 0.38 unit change in frequency, p = 0.02), GET versus SMC (0.42, p = 0.01) and GET versus APT (0.37, p = 0.01). Significantly less joint pain was reported following CBT versus APT (0.35, p = 0.02) and GET versus APT (0.36, p = 0.02). Co-morbid fibromyalgia was less frequent following GET versus SMC (0.03, p = 0.03). The effect sizes of these differences varied between 0.25 and 0.31 for muscle pain and 0.24 and 0.26 for joint pain. Treatment effects on pain were independent of ‘change in fatigue’.

CONCLUSIONS: CBT and GET were more effective in reducing the frequency of both muscle and joint pain than APT and SMC. When compared to SMC, GET also reduced the frequency of co-morbid fibromyalgia; the size of this effect on pain was small.

 

Source: Bourke JH, Johnson AL, Sharpe M, Chalder T, White PD. Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial. Psychol Med. 2014 May;44(7):1545-52. doi: 10.1017/S0033291713002201. Epub 2013 Aug 23. https://www.ncbi.nlm.nih.gov/pubmed/23967878

 

The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome

Abstract:

Ginseng acidic polysaccharide WGPA isolated from the root of Panax ginseng C. A. Meyer was fractionated into WGPA-A and WGPA-N by anion-exchange chromatography. The antifatigue activity of ginseng acidic polysaccharide WGPA has been reported in our previous research. This present study was designed to identify its active component and elucidate the mechanism for preventing chronic fatigue syndrome (CFS).

WGPA, WGPA-A and WGPA-N were orally administered to mice once daily for 15 days. The effects of these compounds on physiological biomarkers of oxidative stress and on the morphology of the mitochondria in striated skeletal muscle were assessed. The results of forced swimming test-induced indicated that WGPA and WGPA-A could lengthen the swimming time, while WGPA-N could not. In addition, malondialdehyde and lactate dehydrogenase levels in serum were enhanced; while those of superoxide dismutase and glutathione peroxidase were lowered. Interestingly, the structural degeneration of mitochondria were all ameliorated.

These findings suggested that WGPA-A is the active component of WGPA, it might have potential therapeutic effects for CFS and the oxidative stress might be involved in the pathogenesis. Our results also provided essential data for a better understanding of the antifatigue effects of P. ginseng extracts.

 

Source: Wang J, Sun C, Zheng Y, Pan H, Zhou Y, Fan Y. The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome. Arch Pharm Res. 2014 Apr;37(4):530-8. doi: 10.1007/s12272-013-0235-y. Epub 2013 Aug 21. https://www.ncbi.nlm.nih.gov/pubmed/23963977

 

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

Abstract:

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers.

Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels.

VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms.

VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted.

TRIAL REGISTRATION: ClinicalTrials.gov NCT00478465.

© 2013 Wiley Periodicals, Inc.

 

Source: Montoya JG, Kogelnik AM, Bhangoo M, Lunn MR, Flamand L, Merrihew LE, Watt T, Kubo JT, Paik J, Desai M. Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J Med Virol. 2013 Dec;85(12):2101-9. doi: 10.1002/jmv.23713. Epub 2013 Aug 19. https://www.ncbi.nlm.nih.gov/pubmed/23959519

 

Biological phenotypes underpin the physio-somatic symptoms of somatization, depression, and chronic fatigue syndrome

Abstract:

OBJECTIVE: Somatization is a symptom cluster characterized by ‘psychosomatic’ symptoms, that is, medically unexplained symptoms, and is a common component of other conditions, including depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This article reviews the data regarding the pathophysiological foundations of ‘psychosomatic’ symptoms and the implications that this has for conceptualization of what may more appropriately be termed physio-somatic symptoms.

METHOD: This narrative review used papers published in PubMed, Scopus, and Google Scholar electronic databases using the keywords: depression and chronic fatigue, depression and somatization, somatization and chronic fatigue syndrome, each combined with inflammation, inflammatory, tryptophan, and cell-mediated immune (CMI).

RESULTS: The physio-somatic symptoms of depression, ME/CFS, and somatization are associated with specific biomarkers of inflammation and CMI activation, which are correlated with, and causally linked to, changes in the tryptophan catabolite (TRYCAT) pathway. Oxidative and nitrosative stress induces damage that increases neoepitopes and autoimmunity that contribute to the immuno-inflammatory processes. These pathways are all known to cause physio-somatic symptoms, including fatigue, malaise, autonomic symptoms, hyperalgesia, intestinal hypermotility, peripheral neuropathy, etc.

CONCLUSION: Biological underpinnings, such as immune-inflammatory pathways, may explain, at least in part, the occurrence of physio-somatic symptoms in depression, somatization, or myalgic encephalomyelitis/chronic fatigue syndrome and thus the clinical overlap among these disorders.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comment in

Source: Anderson G, Berk M, Maes M. Biological phenotypes underpin the physio-somatic symptoms of somatization, depression, and chronic fatigue syndrome. Acta Psychiatr Scand. 2014 Feb;129(2):83-97. doi: 10.1111/acps.12182. Epub 2013 Aug 17. https://www.ncbi.nlm.nih.gov/pubmed/23952563

 

Mechanisms of change underlying the efficacy of cognitive behaviour therapy for chronic fatigue syndrome in a specialist clinic: a mediation analysis

Abstract:

BACKGROUND: Several randomized controlled trials (RCTs) have shown that cognitive behavioural psychotherapy (CBT) is an efficacious treatment for chronic fatigue syndrome (CFS). However, little is known about the mechanisms by which the treatment has its effect. The aim of this study was to investigate potential mechanisms of change underlying the efficacy of CBT for CFS. We applied path analysis and introduce novel model comparison approaches to assess a theoretical CBT model that suggests that fearful cognitions will mediate the relationship between avoidance behaviour and illness outcomes (fatigue and social adjustment).

METHOD: Data from 389 patients with CFS who received CBT in a specialist service in the UK were collected at baseline, at discharge from treatment, and at 3-, 6- and 12-month follow-ups. Path analyses were used to assess possible mediating effects. Model selection using information criteria was used to compare support for competing mediational models.

RESULTS: Path analyses were consistent with the hypothesized model in which fear avoidance beliefs at the 3-month follow-up partially mediate the relationship between avoidance behaviour at discharge and fatigue and social adjustment respectively at 6 months.

CONCLUSIONS: The results strengthen the validity of a theoretical model of CBT by confirming the role of cognitive and behavioural factors in CFS.

 

Source: Stahl D, Rimes KA, Chalder T. Mechanisms of change underlying the efficacy of cognitive behaviour therapy for chronic fatigue syndrome in a specialist clinic: a mediation analysis. Psychol Med. 2014 Apr;44(6):1331-44. doi: 10.1017/S0033291713002006. Epub 2013 Aug 12. https://www.ncbi.nlm.nih.gov/pubmed/23931831

 

Kynurenine Pathway Pathologies: do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)

Abstract:

The definition of dual tryptophan pathways has increased the understanding of the mind-body, body-mind dichotomy. The serotonergic pathway highlights the primary (endogenous) psychiatric disorders. The up-regulation of the kynurenine pathway by physical illnesses can cause neuropathic and immunological disorders1 associated with secondary neuropsychiatric symptoms.

Tryptophan and nicotinamide deficiencies fall within the protein energy malnutrition (PEM) spectrum. They can arise if the kynurenine pathway is stressed by primary or secondary inflammatory conditions and the consequent imbalance of available catabolic/anabolic substrates may adversely influence convalescent phase efficiency. The replacement of depleted or reduced NAD+ levels and other cofactors can perhaps improve the clinical management of these disorders.

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) appear to meet the criteria of a tryptophan-kynurenine pathway disorder with potential neuroimmunological sequelae. Aspects of some of the putative precipitating factors have been previously outlined.2,3 An analysis of the areas of metabolic dysfunction will focus on future directions for research and management.

 

Source: Blankfield A. Kynurenine Pathway Pathologies: do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM). Int J Tryptophan Res. 2013 Jul 21;6(Suppl 1):39-45. doi: 10.4137/IJTR.S11193. Print 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729338/ (Full article)