Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study

Abstract:

OBJECTIVE: To examine the neuropsychological function characterized in subjects with chronic fatigue syndrome (CFS) at the same time controlling for relevant confounding factors. CFS is associated with symptoms of neuropsychological dysfunction. Objective measures of neuropsychological performance have yielded inconsistent results possibly due to sample selection bias, diagnostic heterogeneity, comorbid psychiatric disorders, and medication usage.

METHOD: CFS subjects (n = 58) and well controls (n = 104) from a population-based sample were evaluated, using standardized symptom severity criteria. Subjects who had major psychiatric disorders or took medications known to influence cognition were excluded. Neuropsychological function was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB).

RESULTS: Compared with controls, CFS subjects exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task. CFS subjects also exhibited alterations in working memory as manifested by a less efficient search strategy on the spatial working memory task, fewer % correct responses on the spatial recognition task, and prolonged latency to a correct response on the pattern recognition task. A significantly higher percentage of CFS subjects versus controls exhibited evidence of neuropsychological impairment (defined by performance 1 standard deviation below the CANTAB normative mean) in tasks of motor speed and spatial working memory. Impairment in CFS subjects versus control subjects ranged from 20% versus 4.8% in five-choice movement time (p = .002) to 27.8% versus 10.6% in search strategy on the spatial working memory task (p = .006).

CONCLUSIONS: These results confirm and quantify alterations in motor speed and working memory in CFS subjects independent of comorbid psychiatric disease and medication usage.

 

Source: Majer M, Welberg LA, Capuron L, Miller AH, Pagnoni G, Reeves WC. Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study. Psychosom Med. 2008 Sep;70(7):829-36. doi: 10.1097/PSY.0b013e31817b9793. Epub 2008 Jul 7. https://www.ncbi.nlm.nih.gov/pubmed/18606722

 

Identification of marker genes for differential diagnosis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a clinically defined condition characterized by long-lasting disabling fatigue. Because of the unknown mechanism underlying this syndrome, there still is no specific biomarker for objective assessment of the pathological fatigue. We have compared gene expression profiles in peripheral blood between 11 drug-free patients with CFS and age- and sex-matched healthy subjects using a custom microarray carrying complementary DNA probes for 1,467 stress-responsive genes.

We identified 12 genes whose mRNA levels were changed significantly in CFS patients. Of these 12 genes, quantitative real-time PCR validated the changes in 9 genes encoding granzyme in activated T or natural killer cells (GZMA), energy regulators (ATP5J2, COX5B, and DBI), proteasome subunits (PSMA3 and PSMA4), putative protein kinase c inhibitor (HINT ), GTPase (ARHC), and signal transducers and activators of transcription 5A (STAT5A).

Next, we performed the same microarray analysis on 3 additional CFS patients and 20 other patients with the chief complaint of long-lasting fatigue related to other disorders (non-CFS patients) and found that the relative mRNA expression of 9 genes classified 79% (11/14) of CFS and 85% (17/20) of the non-CFS patients.

Finally, real-time PCR measurements of the levels of the 9 involved mRNAs were done in another group of 18 CFS and 12 non-CFS patients. The expression pattern correctly classified 94% (17/18) of CFS and 92% (11/12) of non-CFS patients. Our results suggest that the defined gene cluster (9 genes) may be useful for detecting pathological responses in CFS patients and for differential diagnosis of this syndrome.

 

Source: Saiki T, Kawai T, Morita K, Ohta M, Saito T, Rokutan K, Ban N. Identification of marker genes for differential diagnosis of chronic fatigue syndrome. Mol Med. 2008 Sep-Oct;14(9-10):599-607. doi: 10.2119/2007-00059.Saiki. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442021/ (Full article)

 

Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery.

Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy control participants. CBT intervention led to a significant improvement in health status, physical activity and cognitive performance. Crucially, CFS patients showed a significant increase in grey matter volume, localized in the lateral prefrontal cortex. This change in cerebral volume was related to improvements in cognitive speed in the CFS patients.

Our findings indicate that the cerebral atrophy associated with CFS is partially reversed after effective CBT. This result provides an example of macroscopic cortical plasticity in the adult human brain, demonstrating a surprisingly dynamic relation between behavioural state and cerebral anatomy. Furthermore, our results reveal a possible neurobiological substrate of psychotherapeutic treatment.

Comment in: Can CBT substantially change grey matter volume in chronic fatigue syndrome? [Brain. 2009]

 

Source: de Lange FP1, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I. Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. Brain. 2008 Aug;131(Pt 8):2172-80. doi: 10.1093/brain/awn140. Epub 2008 Jun 28. http://brain.oxfordjournals.org/content/131/8/2172.long (Full article)

 

Chronic fatigue syndrome: implications for women and their health care providers during the childbearing years

Abstract:

Chronic fatigue syndrome is a complex debilitating medical disorder that affects approximately 4 million persons in the United States, predominantly women. There has been little scientific exploration about the experience of pregnancy, childbirth, and the postpartum period for women with this disorder. A review of the literature and current research findings addressing the epidemiology, diagnosis, symptoms, and treatment of chronic fatigue syndrome are presented, as well as the currently available data regarding the experience of women with chronic fatigue syndrome anticipating or experiencing pregnancy and the postpartum period. Expert opinion is presented along with current evidence to provide guidelines for the care of women with chronic fatigue syndrome during pregnancy, labor and birth, lactation, and the postpartum period.

 

Source: Allen PR. Chronic fatigue syndrome: implications for women and their health care providers during the childbearing years. J Midwifery Womens Health. 2008 Jul-Aug;53(4):289-301; quiz 399. doi: 10.1016/j.jmwh.2007.12.001. https://www.ncbi.nlm.nih.gov/pubmed/18586181

 

Attentional bias towards health-threat information in chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate whether individuals with chronic fatigue syndrome (CFS) show an attentional bias towards health-threat information.

METHODS: Attentional bias (AB) was assessed in individuals with CFS and healthy controls using a visual probe task which presented health-threat and neutral words and pictures for 500 ms. Self-report questionnaires were used to assess CFS symptoms, depression, anxiety, and social desirability.

RESULTS: Compared to a healthy control group, the CFS group showed an enhanced AB towards heath-threat stimuli relative to neutral stimuli. The AB was not influenced by the type of stimulus (pictures vs. words).

CONCLUSION: The finding of an AB towards health-threat information in individuals with CFS is supportive of models of CFS which underlie cognitive behavior therapy.

 

Source: Hou R, Moss-Morris R, Bradley BP, Peveler R, Mogg K. Attentional bias towards health-threat information in chronic fatigue syndrome. J Psychosom Res. 2008 Jul;65(1):47-50. doi: 10.1016/j.jpsychores.2008.03.008. https://www.ncbi.nlm.nih.gov/pubmed/18582611

 

Determinants of health care use in chronic fatigue syndrome patients: a cross-sectional study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is associated with a high use of health care services. To reduce the related costs for patients and society, it will be useful to know which factors determine CFS patients’ amount of health care use. Little is known, however, about these factors.

METHOD: The present study retrospectively performed a cross-sectional analysis to investigate the possible factors determining CFS patients’ health care use. A total of 263 CFS patients, derived from two subgroups (149 from tertiary care and 114 from primary/secondary care), participated. Health care use was measured with a questionnaire asking details on consumption over the past 6 months. Fatigue severity and physical functioning were measured with the subscale Experienced Fatigue of the Checklist Individual Strength (CIS-20) and the subscale Physical Functioning of the SF-36, respectively. Multiple regression analysis, T-tests, and chi(2) tests were performed.

RESULTS: The regression analysis revealed that, after controlling for patient characteristics (explaining 13%), fatigue factors added 4% predictive value and certain perpetuating factors of fatigue, including focus on bodily symptoms and attributions of fatigue, added another 5%. The analysis of subgroups revealed that, compared to the tertiary care population, fewer patients from primary/secondary care had visited a medical specialist (50% vs. 71%), used antidepressants (16% vs. 25%) and tranquilizers (3% vs. 18%), and had spent a night in hospital (7% vs. 10%). However, overall costs of health care between these subgroups did not differ.

CONCLUSIONS: This study showed that illness duration, physical impairment due to fatigue, and psychological perpetuating factors of fatigue do determine the variance in CFS patients’ health care use. These results give clear directions for treating CFS patients and managing health care for CFS.

 

Source: Scheeres K, Wensing M, Severens H, Adang E, Bleijenberg G. Determinants of health care use in chronic fatigue syndrome patients: a cross-sectional study. J Psychosom Res. 2008 Jul;65(1):39-46. doi: 10.1016/j.jpsychores.2008.03.015. Epub 2008 May 22. https://www.ncbi.nlm.nih.gov/pubmed/18582610

 

An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS

Abstract:

BACKGROUND: It has been shown that chronic fatigue syndrome (CFS) and major depression (MDD) are accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS and MDD are accompanied by an IgM-mediated immune response directed against nitro-serum bovine albumin (BSA), which is a neoepitope of BSA formed by damage caused by nitrosative stress.

AIMS: Toward this end, we examined serum IgM antibodies to nitro-BSA in 13 patients with CFS, 14 subjects with partial CFS, 16 patients with MDD and 11 normal controls.

RESULTS: We found that the prevalence and mean values for the serum IgM levels directed against nitro-BSA were significantly greater in patients with partial CFS, CFS and MDD than in normal controls, and significantly greater in CFS than in those with partial CFS and MDD. We found significant and positive correlations between serum IgM levels directed against nitro-BSA and symptoms of the FibroFatigue scale, i.e. aches and pain and muscular tension. There was also a strong positive correlation between serum IgM titers directed against nitro-BSA and an index of increased gut permeability (“leaky gut”), i.e. serum IgM and IgA directed against LPS of different gram-negative enterobacteria.

DISCUSSION: The above mentioned results indicate that both CFS and MDD are accompanied by a) an increased gut permeability which has allowed an exaggerated passage of BSA through a compromised epithelial barrier; b) increased nitrosative stress which has induced damage to BSA; and c) an IgM-mediated immune response which is directed against the nitro-BSA neoepitopes. Nitrosative stress is one of the factors underpinning the comorbidity and clinical overlap between CFS and MDD.

 

Source: Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9. https://www.ncbi.nlm.nih.gov/pubmed/18580855

 

The Energy Envelope Theory and myalgic encephalomyelitis/chronic fatigue syndrome

Erratum in: AAOHN J. 2008 Jul;56(7):288. Muldowney, Kathleen [added]; Torres-Harding, Susan [added].

Abstract:

Individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have little stamina and endurance, and pose a challenge for nursing professionals. The Energy Envelope Theory, which posits that maintaining expended energy levels consistent with available energy levels may reduce the frequency and severity of symptoms, is particularly useful when working with clients with ME/CFS. Anecdotal support from the client community for this theory supports its use as a management tool for ME/CFS, but little formal research has been done in this area.

In this study, a daily energy quotient was established by dividing the expended energy level by the perceived energy level and multiplying by 100. It was predicted that those participants who expended energy beyond their level of perceived energy would have more severe fatigue and symptoms and lower levels of physical and mental functioning.

Findings are congruent with the Energy Envelope Theory as they indicated that the daily energy quotient was related to several indices of functioning including depression, anxiety, fatigue, pain, quality of life, and disability. The overall results provide support for a strategy health care professionals can use when working with clients with ME/CFS.

 

Source: Jason L, Muldowney K, Torres-Harding S. The Energy Envelope Theory and myalgic encephalomyelitis/chronic fatigue syndrome. AAOHN J. 2008 May;56(5):189-95. https://www.ncbi.nlm.nih.gov/pubmed/18578185

 

Glucocorticoid receptor mediated negative feedback in chronic fatigue syndrome using the low dose (0.5 mg) dexamethasone suppression test

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is associated with hypocortisolism, but it is not yet clear the extent to which enhanced negative feedback may underlie this finding.

METHODS: We undertook a low-dose dexamethasone (0.5 mg) suppression test in 18 CFS patients and 20 matched, healthy controls. We measured salivary cortisol levels at 0800 h, 1200 h, 1600 h and 2000 h before and after the administration of 0.5 mg of dexamethasone.

RESULTS: Basal cortisol output was raised in this group of CFS patients compared to controls. Overall, the percentage suppression following dexamethasone administration was no different between CFS (mean+/-sem: 80.4+/-4.4%) and controls (76.2+/-4.9 %). However, the sub-group of patients with CFS and comorbid depression (n=9) showed a significant hypersuppression of salivary cortisol in response to dexamethasone (89.0+/-1.9%; p<0.05 v controls).

LIMITATIONS: The sub-group analysis was on small numbers and should be considered preliminary. Dexamethasone probes only glucocorticoid medicated negative feedback but does not probe mineralocorticoid feedback, the other main physiological feedback mechanism.

CONCLUSION: We found partial support for the hypothesis of enhanced negative feedback in CFS but only in patients with comorbid depression and also in the context of a sample of patients with elevated basal cortisol levels, which is an atypical finding in the literature.

 

Source: Papadopoulos A, Ebrecht M, Roberts AD, Poon L, Rohleder N, Cleare AJ. Glucocorticoid receptor mediated negative feedback in chronic fatigue syndrome using the low dose (0.5 mg) dexamethasone suppression test. J Affect Disord. 2009 Jan;112(1-3):289-94. doi: 10.1016/j.jad.2008.05.001. Epub 2008 Jun 24. https://www.ncbi.nlm.nih.gov/pubmed/18573538

 

Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are poorly understood disorders that share similar demographic and clinical characteristics. The etiology and pathophysiology of these diseases remain unclear. Because of the similarities between both disorders it was suggested that they share a common pathophysiological mechanisms, namely, central nervous system (CNS) dysfunction. Current hypotheses center on atypical sensory processing in the CNS and dysfunction of skeletal muscle nociception and the hypothalamic-pituitary-adrenal (HPA) axis.

Researches suggest that the (CNS) is primarily involved in both disorders in regard to the pain, fatigue and sleep disturbances. Many patients experience difficulty with concentration and memory and many others have mood disturbance, including depression and anxiety. Although fibromyalgia is common and associated with substantial morbidity and disability, there are no US Food and Drug Administration (FDA)-approved treatments except pregabalin.

Recent pharmacological treatment studies about fibromyalgia have focused on selective serotonin and norepinephrine (NE) reuptake inhibitors, which enhance serotonin and NE neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications. CFS is a descriptive term used to define a recognisable pattern of symptoms that cannot be attributed to any alternative condition. The symptoms are currently believed to be the result of disturbed brain function.

To date, no pharmacological agent has been reliably shown to be effective treatment for CFS. Management strategies are therefore primarily directed at relief of symptoms and minimising impediments to recovery. This chapter presents data demonstrating CFS, abnormal pain processing and autonomic nervous system (ANS) dysfunction in FM and CFS and concludes by reviewing the new concepts in treatments in CFS and FM.

 

Source: Gur A, Oktayoglu P. Central nervous system abnormalities in fibromyalgia and chronic fatigue syndrome: new concepts in treatment. Curr Pharm Des. 2008;14(13):1274-94. https://www.ncbi.nlm.nih.gov/pubmed/18537652