Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by persistent emotional, mental, and physical fatigue accompanied by a range of neurological, autonomic, neuroendocrine, immune, and sleep problems. Research has shown that psychosocial factors such as anxiety and depression as well as the symptoms of the illness, have a significant impact on the quality of life of people with ME/CFS. In addition, individuals may suffer from deficits in memory and concentration. This study set out to explore the relationships between variables which have been found to contribute to cognitive performance, as measured by prospective and retrospective memory, and cognitive failures.

METHODS: Eighty-seven people with ME/CFS answered questionnaires measuring fatigue, depression, anxiety, social support, and general self-efficacy. These were used in a correlational design (multiple regression) to predict cognitive function (self-ratings on prospective and retrospective memory), and cognitive failures.

RESULTS: Our study found that fatigue, depression, and general self-efficacy were directly associated with cognitive failures and retrospective (but not prospective) memory.

CONCLUSION: Although it was not possible in this study to determine the cause of the deficits, the literature in this area leads us to suggest that although the pathophysiological mechanisms of ME/CFS are unclear, abnormalities in the immune system, including proinflammatory cytokines, can lead to significant impairments in cognition. We suggest that fatigue and depression may be a result of the neurobiological effects of ME/CFS and in addition, that the neurobiological effects of the illness may give rise to both fatigue and cognitive deficits independently.

 

Source: Attree EA, Arroll MA, Dancey CP, Griffith C, Bansal AS. Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome. Psychol Res Behav Manag. 2014 Feb 25;7:67-76. doi: 10.2147/PRBM.S50645. ECollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940708/ (Full article)

 

Effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase activity and malonaldehyde concentration in chronic fatigue syndrome rats

Abstract:

OBJECTIVE: To observe the effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase (SOD) activity and malonaldehyde (MDA) content in chronic fatigure syndrome (CFS) rats so as to reveal its mechanism underlying improvement of clinical CFS.

METHODS: Thirty-six male SD rats were randomly divided into control group, model group and acupuncture group (n = 12 in each group). CFS model was established by double stress stimulation of suspending (1.0 – 2.5 h increasing gradually) and forced swimming [Morris water maze tasks, 7 min in (10 +/- 1) degrees C water], once daily for 12 days. Manual acupuncture stimulation was applied to “Baihui” (CV 20), bilateral “Zusanli” (ST 36) and “Sanyinjiao” (SP 6), once daily for 21 days (with 3 days’ interval between every two weeks). Learning-memory ability was determined by Morris water maze tests, and SOD activity and MDA concentration in the brain tissues were detected by xanthine oxidase method and thiobarbiturif acid method, respectively.

RESULTS: Compared with the control group, the escape latencies at time-points of day 1, 2, 3, 4 and 5 of Morris water maze tests were significantly longer, the target platform crossing times were markedly fewer and the target platform quadrant staying time obviously shorter, cerebral SOD activity was considerably decreased, and cerebral MDA content remarkably increased in the model group (P < 0.05, P < 0.01). Following acupuncture intervention, the escape latencies at time-points of day 1, 2, 3, 4 and 5 were significantly decreased, both target platform crossing times and staying time, and cerebral SOD activity were apparently increased, as well as cerebral MDA level was markedly lowered in comparison with the model group (P<0.05, P<0.01).

CONCLUSION: Acupuncture intervention can improve the learning-memory ability in CFS rats, which may be related to its effect in regulating metabolism of free radicals in the brain tissues.

 

Source: Liu CZ, Lei B. Effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase activity and malonaldehyde concentration in chronic fatigue syndrome rats.Zhen Ci Yan Jiu. 2013 Dec;38(6):478-81. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/24588031

 

Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs) is classified by the World Health Organization as a disorder of the central nervous system. ME/cfs is an neuro-immune disorder accompanied by chronic low-grade inflammation, increased levels of oxidative and nitrosative stress (O&NS), O&NS-mediated damage to fatty acids, DNA and proteins, autoimmune reactions directed against neoantigens and brain disorders. Mitochondrial dysfunctions have been found in ME/cfs, e.g. lowered ATP production, impaired oxidative phosphorylation and mitochondrial damage.

This paper reviews the pathways that may explain mitochondrial dysfunctions in ME/cfs. Increased levels of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-α, and elastase, and increased O&NS may inhibit mitochondrial respiration, decrease the activities of the electron transport chain and mitochondrial membrane potential, increase mitochondrial membrane permeability, interfere with ATP production and cause mitochondrial shutdown. The activated O&NS pathways may additionally lead to damage of mitochondrial DNA and membranes thus decreasing membrane fluidity. Lowered levels of antioxidants, zinc and coenzyme Q10, and ω3 polyunsaturated fatty acids in ME/cfs may further aggravate the activated immuno-inflammatory and O&NS pathways.

Therefore, it may be concluded that immuno-inflammatory and O&NS pathways may play a role in the mitochondrial dysfunctions and consequently the bioenergetic abnormalities seen in patients with ME/cfs. Defects in ATP production and the electron transport complex, in turn, are associated with an elevated production of superoxide and hydrogen peroxide in mitochondria creating adaptive and synergistic damage.

It is argued that mitochondrial dysfunctions, e.g. lowered ATP production, may play a role in the onset of ME/cfs symptoms, e.g. fatigue and post exertional malaise, and may explain in part the central metabolic abnormalities observed in ME/cfs, e.g. glucose hypometabolism and cerebral hypoperfusion.

 

Source: Morris G, Maes M. Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways. Metab Brain Dis. 2014 Mar;29(1):19-36. doi: 10.1007/s11011-013-9435-x. Epub 2013 Sep 10.https://www.ncbi.nlm.nih.gov/pubmed/24557875

 

Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial

Abstract:

OBJECTIVE: Temporal summation (TS) of pain, conditioned pain modulation (CPM), and exercise-induced analgesia (EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia (CFS/FM), and patients with rheumatoid arthritis (RA), both under placebo and paracetamol condition.

METHODS: Fifty-three female volunteers – of which 19 patients with CFS/FM, 16 patients with RA, and 18 healthy controls – underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS and CPM.

RESULTS: Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo (P < 0.05). In patients with CFS/FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen.

CONCLUSION: This study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/FM, these positive effects were only observed after paracetamol and results were inconsistent.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01154647.

 

Source: Meeus M, Hermans L, Ickmans K, Struyf F, Van Cauwenbergh D, Bronckaerts L, De Clerck LS, Moorken G, Hans G, Grosemans S, Nijs J. Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial. Pain Pract. 2015 Feb;15(2):98-106. doi: 10.1111/papr.12181. Epub 2014 Feb 17. https://www.ncbi.nlm.nih.gov/pubmed/24528544

 

Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis

Abstract:

BACKGROUND: Considerable controversy has transpired regarding the core features of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Current case definitions differ in the number and types of symptoms required. This ambiguity impedes the search for biological markers and effective treatments.

PURPOSE: This study sought to empirically operationalize symptom criteria and identify which symptoms best characterize the illness.

METHODS: Patients (n=236) and controls (n=86) completed the DePaul Symptom Questionnaire, rating the frequency and severity of 54 symptoms. Responses were compared to determine the threshold of frequency/severity ratings that best distinguished patients from controls. A Classification and Regression Tree (CART) algorithm was used to identify the combination of symptoms that most accurately classified patients and controls.

RESULTS: A third of controls met the symptom criteria of a common CFS case definition when just symptom presence was required; however, when frequency/severity requirements were raised, only 5% met criteria. Employing these higher frequency/severity requirements, the CART algorithm identified three symptoms that accurately classified 95.4% of participants as patient or control: fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.

CONCLUSIONS: Minimum frequency/severity thresholds should be specified in symptom criteria to reduce the likelihood of misclassification. Future research should continue to seek empirical support of the core symptoms of ME and CFS to further progress the search for biological markers and treatments.

 

Source: Jason LA, Sunnquist M, Brown A, Evans M, Vernon SD, Furst J, Simonis V. Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis. Fatigue. 2014 Jan 1;2(1):40-56. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912876/ (Full article)

 

Are Myalgic Encephalomyelitis and chronic fatigue syndrome different illnesses? A preliminary analysis

Abstract:

Considerable discussion has transpired regarding whether chronic fatigue syndrome is a distinct illness from Myalgic Encephalomyelitis. A prior study contrasted the Myalgic Encephalomyelitis International Consensus Criteria with the Fukuda and colleagues’ chronic fatigue syndrome criteria and found that the Myalgic Encephalomyelitis International Consensus Criteria identified a subset of patients with greater functional impairment and physical, mental, and cognitive problems than the larger group who met Fukuda and colleagues’ criteria. The current study analyzed two discrete data sets and found that the Myalgic Encephalomyelitis International Consensus Criteria identified more impaired individuals with more severe symptomatology.

© The Author(s) 2014.

 

Source: Jason LA, Sunnquist M, Brown A, Evans M, Newton JL. Are Myalgic Encephalomyelitis and chronic fatigue syndrome different illnesses? A preliminary analysis. J Health Psychol. 2016 Jan;21(1):3-15. doi: 10.1177/1359105313520335. Epub 2014 Feb 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125561/ (Full article)

 

Influence of graded exercise therapy on anxiety levels and health-related quality of life in chronic fatigue syndrome

Abstract:

AIM: The purpose of the present study was twofold: 1) to determine to what extent graded exercise therapy (GET) improves health-related quality of life (HRQOL) and anxiety levels in patients with chronic fatigue syndrome (CFS); and 2) to correlate scores of HRQOL and anxiety levels in CFS patients.

METHODS:Anxiety and HRQOL were assessed in 26 CFS patients before and after 12 weeks of GET. Anxiety wa s measured using the State-Trait Anxiety Inventory questionnaire (STAI) and HRQOL using the Medical Outcomes Study Short-Form questionnaire (SF-36).

RESULTS: GET significantly decreased trait anxiety (STAI-T) levels in patients with CFS. Patients’ scores on SF-36 following GET showed higher levels of functioning, but only the “vitality” subscale scores showed a statistically significant difference. A negative correlation was present between all eight subscales of SF-36 and anxiety levels. The strongest negative correlation for both state and trait anxiety scores (STAI-S and STAI-T) was found with the scores on the “Limitations due to emotional problems” subscale of SF-36 (r=-0.69 and r=-0.55, respectively), while the weakest negative correlation was with the “Physical functioning” subscale scores (r=-0.30 and r=-0.31, respectively).

CONCLUSION: Graded exercise therapy has a positive effect on both physical and psychological state of CFS patients. GET can decrease anxiety and improve quality of life of CFS patients. CFS patients with higher state and trait anxiety levels have lower quality of life, and vice versa.

 

Source: Klasnja A, Grujic N, Popadic Gacesa J, Barak O, Tomic S, Brkic S. Influence of graded exercise therapy on anxiety levels and health-related quality of life in chronic fatigue syndrome. J Sports Med Phys Fitness. 2014 Apr;54(2):210-5. https://www.ncbi.nlm.nih.gov/pubmed/24509993

 

Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review

Abstract:

OBJECTIVE: To identify case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and explore how the validity of case definitions can be evaluated in the absence of a reference standard.

DESIGN: Systematic review.

SETTING: International.

PARTICIPANTS: A literature search, updated as of November 2013, led to the identification of 20 case definitions and inclusion of 38 validation studies.

PRIMARY AND SECONDARY OUTCOME MEASURE: Validation studies were assessed for risk of bias and categorised according to three validation models: (1) independent application of several case definitions on the same population, (2) sequential application of different case definitions on patients diagnosed with CFS/ME with one set of diagnostic criteria or (3) comparison of prevalence estimates from different case definitions applied on different populations.

RESULTS: A total of 38 studies contributed data of sufficient quality and consistency for evaluation of validity, with CDC-1994/Fukuda as the most frequently applied case definition. No study rigorously assessed the reproducibility or feasibility of case definitions. Validation studies were small with methodological weaknesses and inconsistent results. No empirical data indicated that any case definition specifically identified patients with a neuroimmunological condition.

CONCLUSIONS: Classification of patients according to severity and symptom patterns, aiming to predict prognosis or effectiveness of therapy, seems useful. Development of further case definitions of CFS/ME should be given a low priority. Consistency in research can be achieved by applying diagnostic criteria that have been subjected to systematic evaluation.

 

Source: Brurberg KG, Fønhus MS, Larun L, Flottorp S, Malterud K. Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. BMJ Open. 2014 Feb 7;4(2):e003973. doi: 10.1136/bmjopen-2013-003973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918975/ (Full article)

 

Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial

Abstract:

IMPORTANCE: Chronic fatigue syndrome (CFS) is a disabling condition with unknown disease mechanisms and few treatment options.

OBJECTIVE: To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function.

DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled from a single referral center recruiting nationwide in Norway. A referred sample of 176 adolescents with CFS was assessed for eligibility; 120 were included (34 males and 86 females; mean age, 15.4 years). A volunteer sample of 68 healthy adolescents serving as controls was included (22 males and 46 females; mean age, 15.1 years). The CSF patients and healthy controls were assessed cross-sectionally at baseline. Thereafter, patients with CFS were randomized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks; double-blinding was provided. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.

INTERVENTIONS: Clonidine hydrochloride capsules (25 µg or 50 µg twice daily for body weight <35 kg or >35 kg, respectively) vs placebo capsules for 9 weeks.

MAIN OUTCOMES AND MEASURES: Number of steps per day.

RESULTS: At baseline, patients with CFS had a lower number of steps per day (P < .001), digit span backward score (P = .002), and urinary cortisol to creatinine ratio (P = .001), and a higher fatigue score (P < .001), heart rate responsiveness (P = .02), plasma norepinephrine level (P < .001), and serum C-reactive protein concentration (P = .04) compared with healthy controls. There were no significant differences regarding blood microbiology evaluation. During intervention, the clonidine group had a lower number of steps per day (mean difference, -637 steps; P = .07), lower plasma norepinephrine level (mean difference, -42 pg/mL; P = .01), and lower serum C-reactive protein concentration (mean ratio, 0.69; P = .02) compared with the CFS placebo group.

CONCLUSIONS AND RELEVANCE: Adolescent CFS is associated with enhanced sympathetic nervous activity, low-grade systemic inflammation, attenuated hypothalamus-pituitary-adrenal axis function, cognitive impairment, and large activity reduction, but not with common microorganisms. Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity; thus, sympathetic and inflammatory enhancement may be compensatory mechanisms. Low-dose clonidine is not clinically useful in CFS.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01040429.

 

Source: Sulheim D, Fagermoen E, Winger A, Andersen AM, Godang K, Müller F, Rowe PC, Saul JP, Skovlund E, Øie MG, Wyller VB. Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial. JAMA Pediatr. 2014 Apr;168(4):351-60. doi: 10.1001/jamapediatrics.2013.4647. https://www.ncbi.nlm.nih.gov/pubmed/24493300

 

Living with the unexplained: coping, distress, and depression among women with chronic fatigue syndrome and/or fibromyalgia compared to an autoimmune disorder

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia are disabling conditions without objective diagnostic tests, clear-cut treatments, or established etiologies. Those with the disorders are viewed suspiciously, and claims of malingering are common, thus promoting further distress. It was hypothesized in the current study that levels of unsupportive social interactions and the coping styles used among those with CFS/fibromyalgia would be associated with perceived distress and depressive symptoms.

Women with CFS/fibromyalgia (n=39), in fact, reported higher depression scores, greater perceived distress and more frequent unsupportive relationships than healthy women (n=55), whereas those with a chronic, but medically accepted illness comprising an autoimmune disorder (lupus erythematosus, multiple sclerosis, rheumatoid arthritis; n=28), displayed intermediate scores. High problem-focused coping was associated with low levels of depression and perceived distress in those with an autoimmune condition.

In contrast, although CFS/fibromyalgia was also accompanied by higher depression scores and higher perceived distress, this occurred irrespective of problem-focused coping. It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia.

 

Source: McInnis OA, Matheson K, Anisman H. Living with the unexplained: coping, distress, and depression among women with chronic fatigue syndrome and/or fibromyalgia compared to an autoimmune disorder. Anxiety Stress Coping. 2014;27(6):601-18. doi: 10.1080/10615806.2014.888060. Epub 2014 Mar 3. https://www.ncbi.nlm.nih.gov/pubmed/24479644