A twin study of cognitive function in chronic fatigue syndrome: the effects of sudden illness onset

Abstract:

Variable reports of neuropsychological deficits in individuals with chronic fatigue syndrome (CFS) may, in part, be attributable to methodological limitations. In this study, these limitations were addressed by controlling for genetic and environmental influences and by assessing the effects of comorbid depression and mode of illness onset. Specifically, the researchers conducted a co-twin control study of 22 pairs of monozygotic twins, in which 1 twin met strict criteria for CFS and the co-twin was healthy.

Twins underwent a structured psychiatric interview and comprehensive neuropsychological assessment evaluating 6 cognitive domains. Results indicated that twin groups had similar intellectual and visual memory functioning, but fatigued twins exhibited decreases in motor functions (p = .05), speed of information processing (p = .02), verbal memory (p = .02), and executive functioning (p = .01). Major depression did not affect neuropsychological functioning among fatigued twins, although twins with sudden illness onset demonstrated slowed information processing compared with those with gradual onset (p = .01).

Sudden onset CFS was associated with reduced speed of information processing. If confirmed, these findings suggest the need to distinguish illness onset in future CFS studies and may have implications for treatment, cognitive rehabilitation, and disability determination.

 

Source: Claypoole KH, Noonan C, Mahurin RK, Goldberg J, Erickson T, Buchwald D. A twin study of cognitive function in chronic fatigue syndrome: the effects of sudden illness onset. Neuropsychology. 2007 Jul;21(4):507-13. https://www.ncbi.nlm.nih.gov/pubmed/17605583

 

School phobia and childhood chronic fatigue syndrome (CCFS)

Abstract:

Chronic fatigue occurring in previously healthy children and adolescents is a vexing problem encountered by pediatric practitioners and the impact of fatigue in youngsters should not be underestimated. In its severe form, it is often associated with mood disorders. Findings in children and adolescent cases suggest that severe unexplained fatigue might precede the development of fatigue-related illness, such as childhood chronic fatigue syndrome (CCFS). This is a disabling condition characterized by severe disabling fatigue and a combination of symptoms, the prominent features being self-reported impairments in concentration and short-term memory, sleep disturbances and autonomic symptoms that cannot be explained by medical or psychiatric illness. We have encountered such patients with these complaints; their major symptoms include: general fatigue, fever, headache (not migraine), and memory disturbance. From our clinical experience, we have inferred that patients with CCFS might experience changes in brain function levels, which induce an autonomic imbalance and engender symptoms such as general fatigue, higher-order level cognitive dysfunction, and memory disturbance.

 

Source: Tomoda A. School phobia and childhood chronic fatigue syndrome (CCFS). Nihon Rinsho. 2007 Jun;65(6):1121-33. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561707

 

The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) often have concentration and memory problems. Neuropsychological test performance is impaired in at least a subgroup of patients with CFS. Cognitive behavioural therapy (CBT) for CFS leads to a reduction in fatigue and disabilities.

AIM: To test the hypothesis that CBT results in a reduction of self-reported cognitive impairment and in an improved neuropsychological test performance.

METHODS: Data of two previous randomised controlled trials were used. One study compared CBT for adult patients with CFS, with two control conditions. The second study compared CBT for adolescent patients with a waiting list condition. Self-reported cognitive impairment was assessed with questionnaires. Information speed was measured with simple and choice reaction time tasks. Adults also completed the symbol digit-modalities task, a measure of complex attentional function.

RESULTS: In both studies, the level of self-reported cognitive impairment decreased significantly more after CBT than in the control conditions. Neuropsychological test performance did not improve.

CONCLUSIONS: CBT leads to a reduction in self-reported cognitive impairment, but not to improved neuropsychological test performance. The findings of this study support the idea that the distorted perception of cognitive processes is more central to CFS than actual cognitive performance.

 

Source: Knoop H, Prins JB, Stulemeijer M, van der Meer JW, Bleijenberg G. The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance. J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):434-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077788/ (Full article)

 

Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) patients often have memory and cognitive complaints. Objective cognitive testing demonstrates long-term and working memory impairments. In addition, CFS patients have slow information-processing, and FM patients have impaired control of attention, perhaps due to chronic pain. Neuroimaging studies demonstrate cerebral abnormalities and a pattern of increased neural recruitment during cognitive tasks. Future work should focus on the specific neurocognitive systems involved in cognitive dysfunction in each syndrome.

 

Source: Glass JM. Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions. Curr Rheumatol Rep. 2006 Dec;8(6):425-9. https://www.ncbi.nlm.nih.gov/pubmed/17092441

 

Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task

Abstract:

OBJECTIVE: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive difficulties. However, objective evidence supporting these claims is inconsistent. The present functional magnetic resonance imaging study examined the neural correlates of working memory in patients with CFS compared with controls.

METHODS: Seventeen patients with CFS and 12 healthy control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-, and 3-back).

RESULTS: Both groups performed comparably well and activated the verbal working memory network during all task levels. However, during the 1-back condition, patients with CFS showed greater activation than control subjects in medial prefrontal regions, including the anterior cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back conditions, patients but not control subjects significantly activated a large cluster in the right inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant differences in brain activation between the two groups as the demands of the task increased.

CONCLUSIONS: These results suggest that patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects. It remains to be determined whether these findings stay stable after successful treatment.

 

Source: Caseras X, Mataix-Cols D, Giampietro V, Rimes KA, Brammer M, Zelaya F, Chalder T, Godfrey EL. Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task. Psychosom Med. 2006 Nov-Dec;68(6):947-55. Epub 2006 Nov 1. https://www.ncbi.nlm.nih.gov/pubmed/17079703

 

Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) frequently complain of cognitive dysfunction. However, evidence of cognitive impairment in CFS patients has been found in some, but not other, studies. This heterogeneity in findings may stem from the relative presence of mental fatigue in the patient populations examined. The present study assessed this possibility in a population-based sample of CFS patients.

In all, 43 patients with CFS defined by the criteria of the 1994 research case definition using measurements recommended by the 2003 International CFS Study Group, and 53 age-, sex-, and race/ethnicity-matched nonfatigued subjects were included in the study. Mental fatigue was assessed using the mental fatigue subscale of the multidimensional fatigue inventory. Cognitive function was evaluated using an automated battery of computerized tests (Cambridge neuropsychological test automated battery (CANTAB)) that assessed psychomotor function, planning and problem-solving abilities, and memory and attentional performance.

CFS patients with significant complaints of mental fatigue (score of mental fatigue 2 standard deviations above the mean of nonfatigued subjects) exhibited significant impairment in the spatial working memory and sustained attention (rapid visual information processing) tasks when compared to CFS patients with low complaints of mental fatigue and nonfatigued subjects. In CFS patients with significant mental fatigue, sustained attention performance was impaired only in the final stages of the test, indicating greater cognitive fatigability in these patients. CFS patients with low mental fatigue displayed performance comparable to nonfatigued subjects on all tests of the CANTAB battery. These findings show strong concordance between subjective complaints of mental fatigue and objective measurement of cognitive impairment in CFS patients and suggest that mental fatigue is an important component of CFS-related cognitive dysfunction.

 

Source: Capuron L, Welberg L, Heim C, Wagner D, Solomon L, Papanicolaou DA, Craddock RC, Miller AH, Reeves WC. Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome. Neuropsychopharmacology. 2006 Aug;31(8):1777-84. Epub 2006 Jan 4. http://www.nature.com/npp/journal/v31/n8/full/1301005a.html (Full article)

 

Cognitive function and psychological characteristics of patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate the cognitive function and psychological characteristics of the patients with chronic fatigue syndrome (CFS) in China and analyze its relation with primary psychological diseases.

METHODS: Ninety-one patients with CFS who visited the People’s Hospital, Peking University, in Beijing from Beijing, Shanghai, Tianjin, Heilongjiang, Jilin, Hebei, Inner Mongolia, Shanxi, Shandong, Sichuan, Gansu, Fujian, and Guangdong, 42 males and 49 females, aged 37 +/- 7, 43% of which had the record of formal schooling of regular college course or over and 21 of which had the record of formal schooling of college for professional training, and 58% of which showed clear causes, diagnosed by the CDC criteria 1994, underwent case history collection, physical examination, necessary laboratory test, memory test, and SCL-90, Hamilton depression rating scale (HAMD), and Hamilton anxiety rating scale (HAMA) testing. Thirty healthy persons, 14 males and 16 females, aged 37 +/- 7, were used as controls., A table of case file was established based on the CDC criteria 1994 for each patient to record the relevant data. Independent-Samples T Test was used to compare the memory quotient, the total score and general mean score of SCL-90, the score of HAMD and HAMA. Analyzed the impairment of cognitive function and psychological characteristics of patients with CFS.

RESULTS: The most common symptoms was descent of remembrance and/or attention (82/91, 90%). The memory quotient of the CFS patients was 85 +/- 14, significantly lower than that of the healthy controls (98 +/- 12, t = 4.627, P = 0.000). The total score of SCL-90 of the CFS patients was 192 +/- 47, significantly higher than that of the healthy controls (140 +/- 46, t = 5.297, P = 0.000). The symptoms with a factor score > or = 2.0 in SCL-90 included obsessive-compulsive symptoms (61/91, 67%), somatization (61/91, 67 %), depression (57/91, 63%), and anxiety (49/91, 54%). The HAMD score of the CFS patients was 9.9 +/- 6.1, significantly higher than that of the healthy controls (6.5 +/- 2.5, t = 2.948, P = 0.004). The HAMA score of the CFS patients was 9.9 +/- 7.0, significantly higher than that of the healthy controls (5.9 +/- 2.9, t = 3.015, P = 0.003).

CONCLUSION: The CFS patients in China have an obvious impairment of remembrance and show different psychological abnormalities that are different from those of the patients with primary psychological diseases.

 

Source: Li YJ, Gao XG, Wang DX, Lin T, Bai XL, Yang FZ. Cognitive function and psychological characteristics of patients with chronic fatigue syndrome. Zhonghua Yi Xue Za Zhi. 2005 Nov 2;85(41):2926-9. [Article in Chinese] http://www.ncbi.nlm.nih.gov/pubmed/16324367

 

Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory

Abstract:

Individuals with Chronic Fatigue Syndrome (CFS) often have difficulties with complex auditory information processing. In a series of two Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) studies, we compared BOLD signal changes between Controls and individuals with CFS who had documented difficulties in complex auditory information processing (Study 1) and those who did not (Study 2) in response to performance on a simple auditory monitoring and a complex auditory information processing task (mPASAT).

We hypothesized that under conditions of cognitive challenge: (1) individuals with CFS who have auditory information processing difficulties will utilize frontal and parietal brain regions to a greater extent than Controls and (2) these differences will be maintained even when objective difficulties in this domain are controlled for.

Using blocked design fMRI paradigms in both studies, we first presented the auditory monitoring task followed by the mPASAT. Within and between regions of interest (ROI), group analyses were performed for both studies with statistical parametric mapping (SPM99).

Findings showed that individuals with CFS are able to process challenging auditory information as accurately as Controls but utilize more extensive regions of the network associated with the verbal WM system. Individuals with CFS appear to have to exert greater effort to process auditory information as effectively as demographically similar healthy adults. Our findings provide objective evidence for the subjective experience of cognitive difficulties in individuals with CFS.

 

Source: Lange G, Steffener J, Cook DB, Bly BM, Christodoulou C, Liu WC, Deluca J, Natelson BH. Objective evidence of cognitive complaints in Chronic Fatigue Syndrome: a BOLD fMRI study of verbal working memory. Neuroimage. 2005 Jun;26(2):513-24. Epub 2005 Apr 7. http://www.ncbi.nlm.nih.gov/pubmed/15907308

 

Neural correlates of the chronic fatigue syndrome–an fMRI study

Abstract:

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS.

We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups.

Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error.

Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

 

Source: de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, Toni I. Neural correlates of the chronic fatigue syndrome–an fMRI study. Brain. 2004 Sep;127(Pt 9):1948-57. Epub 2004 Jul 7. http://brain.oxfordjournals.org/content/127/9/1948.long (Full article)

 

Cognitive processing in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

Twenty-one pairs of monozygotic twins discordant for chronic fatigue syndrome (CFS) and 21 matched healthy control (HC) subjects were assessed with 5 untimed tests and 5 timed tests from the computer-based NeuroCognitive Assessment Battery (R. K. Mahurin, 1993). Random effects regression showed no difference between CFS and healthy twins on any of the cognitive tests. Further, the twin groups did not differ from the HC group on any content-dependent measure. In contrast, both sets of twins performed worse than the HC group on all speed-dependent tests except Finger Tapping. Self-rated fatigue and dysphoric mood were only weakly correlated with cognitive performance.

These data point toward a shared genetic trait related to information processing that is manifest in the CFS context. The findings have implications for differentiating genetic and acquired vulnerability in the symptomatic expression of the disorder. ((c) 2004 APA, all rights reserved)

 

Source: Mahurin RK, Claypoole KH, Goldberg JH, Arguelles L, Ashton S, Buchwald D. Cognitive processing in monozygotic twins discordant for chronic fatigue syndrome. Neuropsychology. 2004 Apr;18(2):232-9. http://www.ncbi.nlm.nih.gov/pubmed/15099145