Using an interleukin-6 challenge to evaluate neuropsychological performance in chronic fatigue syndrome

Abstract:

BACKGROUND: Individuals with acute infections experience a range of symptoms including fatigue, malaise, muscle aches, and difficulties with concentration and memory that are usually self-limited. This cluster of symptoms is otherwise, similar to those that characterize chronic fatigue syndrome (CFS). The goal of the present study was to evaluate the cognitive and psychological functioning of CFS patients and normal controls (NCs) when they both were experiencing acute influenza-like symptoms. To induce influenza-like symptoms, we administered interleukin-6 (IL-6), a cytokine that temporarily activates the acute phase immunological and endocrine responses.

METHODS: Nineteen patients who met the 1994 International CFS Study Group Criteria and ten normal controls (NCs) completed routine clinical evaluations, neuropsychological tests of short-term memory, selective attention, and executive control, and self-ratings of somatic symptoms and psychological mood before, shortly following, and 1 day after IL-6 administration.

RESULTS: CFS patients consistently reported more somatic symptoms, even when both groups perceived that they were ill. Both groups somatic symptoms increased during the IL-6 challenge, but the CFS patients symptoms increased more rapidly than controls. In general, the CFS patients performed similarly to NCs on the cognitive measures before, during, and after the IL-6. In contrast to predictions, IL-6 provocation did not impair the cognitive performance of either CFS patients or NCs.

CONCLUSIONS: The IL-6 provocation exacerbated the patients self-reported symptoms but did not reveal notable cognitive impairments between patients and controls during cytokine-induced acute influenza-like symptoms.

 

Source: Arnold MC, Papanicolaou DA, O’Grady JA, Lotsikas A, Dale JK, Straus SE, Grafman J. Using an interleukin-6 challenge to evaluate neuropsychological performance in chronic fatigue syndrome. Psychol Med. 2002 Aug;32(6):1075-89. http://www.ncbi.nlm.nih.gov/pubmed/12214788

 

Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal

Abstract:

RATIONALE: Subjective and objective impairments in neuropsychological function have been reported in chronic fatigue syndrome (CFS) patients under conditions of high arousal. These impairments may reflect impaired central noradrenaline function such as impaired post-synaptic alpha-2 adrenoceptor function.

OBJECTIVES: To determine whether high-dose clonidine has greater agonist effects at central post-synaptic alpha-2 receptors in CFS patients than controls under conditions of high arousal. As a result clonidine may reverse neuropsychological deficits underlying symptoms of poor concentration and memory.

METHODS: High-dose clonidine (2.5 mg/kg) and placebo challenge tests were given in random order to ten medication-free CFS patients without anxiety disorders, depressive disorders or migraine and ten matched healthy controls under the same stressors (timed neuropsychological testing, venous sampling, intravenous drug administration). Growth hormone, cortisol, blood pressure, pulse rate, visual analogue scales of subjective neuropsychological performance and the performance on several tests from a computerised neuropsychological battery were measured.

RESULTS: In CFS patients versus controls, clonidine enhanced both growth hormone ( P = 0.028) and cortisol release ( P = 0.021) and increased speed in the initial stage of a planning task ( P = 0.023). There were no other differences between CFS patients and controls on hormonal, physiological, symptomatic or neuropsychological measures.

CONCLUSIONS: Under conditions of high arousal, CFS patients may display supersensitive central post-synaptic alpha-2 adrenoceptor function associated with the release of cortisol and growth hormone and initial thinking time in planning tasks.

 

Source: Morriss RK, Robson MJ, Deakin JF. Neuropsychological performance and noradrenaline function in chronic fatigue syndrome under conditions of high arousal. Psychopharmacology (Berl). 2002 Sep;163(2):166-73. Epub 2002 Jul 30. http://www.ncbi.nlm.nih.gov/pubmed/12202963

 

Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety, and fatigue

Abstract:

OBJECTIVE: This study was designed to investigate the role of depression, anxiety, and fatigue in Chronic Fatigue Syndrome (CFS) sufferers’ objective and subjective cognitive performance.

METHODS: Twenty-three CFS sufferers and 23 healthy control participants were compared on objective and subjective assessments of cognitive performance. Depression, anxiety, and fatigue were also evaluated.

RESULTS: CFS sufferers did not demonstrate any impairment in objective cognitive functioning compared to the control group, and objective performance was not related to their higher levels of depression or their level of fatigue. Depression scores only accounted for a small amount of the variance in CFS sufferers’ lower subjective assessment of their cognitive performance compared to control participants. There were no differences between the groups on anxiety scores.

CONCLUSION: The results are discussed in terms of the heterogeneity of the CFS population and the complex interaction of symptomatological factors that characterise CFS.

 

Source: Short K, McCabe M, Tooley G. Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety, and fatigue. J Psychosom Res. 2002 Jun;52(6):475-83. http://www.ncbi.nlm.nih.gov/pubmed/12069872

 

Perception of cognitive performance in patients with chronic fatigue syndrome

Abstract:

This study examined discrepancies between perceived and actual performance by patients with chronic fatigue syndrome (CFS) confronted with a challenging cognitive task. Before and after completing a modified version of the Stroop task, 40 patients and 40 healthy control participants estimated their own performance and the performance that would normally be achieved by someone of equal age and education level. After correcting for differences between the groups in depression, we found no differences in actual performance on the Stroop. However, patients with CFS consistently underestimated their performance relative to normal performance. This difference was observed for both depressed and nondepressed subgroups of patients, persisted after adjusting the results for depression, and correlated with patients’ ratings of the mental effort and fatigue evoked by the task. The results are discussed in light of cognitive models of CFS that suggest the setting of impossibly high standards of personal performance may contribute to the dynamism of this disease.

 

Source: Metzger FA, Denney DR. Perception of cognitive performance in patients with chronic fatigue syndrome. Ann Behav Med. 2002 Spring;24(2):106-12. http://www.ncbi.nlm.nih.gov/pubmed/12054315

 

The relations among body consciousness, somatic symptom report, and information processing speed inchronic fatigue syndrome

Abstract:

OBJECTIVE: The aim of this study was to assess the potential influence of body consciousness and levels of somatic symptom report upon information processing speed in patients with chronic fatigue syndrome (CFS).

BACKGROUND: According to a model of a fixed information processing capacity, it was predicted that in a group of patients with CFS, high body consciousness in combination with a high report of somatic symptoms would affect information-processing speed negatively.

METHODS: Information- and motor-processing speed were simultaneously measured with a simple- and a choice-reaction time task, whereas cognitive complaints were rated with two questionnaires. The hypothesized influence of private body consciousness and somatic symptom report upon information-processing speed was tested in a model. A symptom-validity test was used to screen for possible illness behavior.

RESULTS: Private body consciousness was directly related to information-processing speed and somatic symptom report. Somatic symptom report was related to both test performance and memory and concentration complaints.

CONCLUSIONS: Levels of private body consciousness directly affected somatic symptom report and information-processing speed. This finding supports the role of attentive processes in CFS, and offers, besides possible cerebral dysfunction, an alternative explanation for slowing of information processing in CFS.

 

Source: van der Werf SP, de Vree B, van Der Meer JW, Bleijenberg G. The relations among body consciousness, somatic symptom report, and information processing speed in chronic fatigue syndrome. Neuropsychiatry Neuropsychol Behav Neurol. 2002 Mar;15(1):2-9. http://www.ncbi.nlm.nih.gov/pubmed/11877546

 

Information processing in chronic fatigue syndrome: a preliminary investigation of suggestibility

Abstract:

This study examines the effects of certain types of information processing on the subjective experience of cognitive deficits in persons with chronic fatigue syndrome (CFS).

Two groups of participants, persons with CFS and a group of healthy controls, were administered a symptom inventory and measures of intellectual functioning, memory, automatic processing, and suggestibility. The groups differed significantly on number and severity of reported symptoms and on measures of global suggestibility and automatic processing, but not on measures of intellectual functioning and memory.

Suggestibility was related to number and severity of reported symptoms, as well as the inability to inhibit the automatic processing of information. Implications of these findings are discussed, as well as directions for future research and treatment of symptoms associated with CFS.

 

Source: DiClementi JD, Schmaling KB, Jones JF. Information processing in chronic fatigue syndrome: a preliminary investigation of suggestibility. J Psychosom Res. 2001 Nov;51(5):679-86. http://www.ncbi.nlm.nih.gov/pubmed/11728509

 

Intraindividual variability in cognitive performance in persons with chronic fatigue syndrome

Abstract:

Studies of cognitive performance among persons with chronic fatigue syndrome (CFS) have yielded inconsistent results. We sought to contribute to findings in this area by examining intraindividual variability as well as level of performance in cognitive functioning.

A battery of cognitive measures was administered to 14 CFS patients and 16 healthy individuals on 10 weekly occasions. Analyses comparing the two groups in terms of level of performance defined by latency and accuracy scores revealed that the CFS patients were slower but not less accurate than healthy persons.

The CFS group showed greater intraindividual variability (as measured by intraindividual standard deviations and coefficients of variation) than the healthy group, although the results varied by task and time frame. Intraindividual variability was found to be stable across time and correlated across tasks at each testing occasion. Intraindividual variability also uniquely differentiated the groups. The present findings support the proposition that intraindividual variability is a meaningful indicator of cognitive functioning in CFS patients.

 

Source: Fuentes K, Hunter MA, Strauss E, Hultsch DF. Intraindividual variability in cognitive performance in persons with chronic fatigue syndrome. Clin Neuropsychol. 2001 May;15(2):210-27. http://www.ncbi.nlm.nih.gov/pubmed/11528543

 

Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders

Abstract:

OBJECTIVE: To identify antinuclear antibodies (ANA) specific for chronic fatigue syndrome (CFS), and in related conditions such as fibromyalgia (FM) or psychiatric disorders.

METHODS: One hundred and fourteen CFS patients and 125 primary and secondary FM patients were selected based on criteria advocated by the Centers for Disease Control and Prevention and by the American College of Rheumatology, respectively. As controls, healthy subjects and patients with either various psychiatric disorders or diffuse connective tissue diseases were included. Autoantibodies were examined by immunoblot utilizing HeLa cell extracts as the antigen.

RESULTS: Autoantibodies to a 68/48 kDa protein were present in 13.2 and 15.6% of patients with CFS and primary FM, respectively. In addition, autoantibodies to a 45 kDa protein were found in 37.1 and 21.6% of the patients with secondary FM and psychiatric disorders, respectively. Meanwhile, these two autoantibodies were not found at all in connective tissue disease patients without FM, nor in healthy subjects (P<0.05). As a group, the anti-68/48 kDa-positive CFS patients presented more frequently with hypersomnia (P<0.005), short-term amnesia (P<0.07) or difficulty in concentration (P<0.05) than those CFS patients without the antibodies.

CONCLUSIONS: The presence of the anti-68/48 kDa protein antibodies in a portion of both CFS and primary FM patients suggests the existence of a common immunological background. These antibodies may find utility as possible markers for a clinicoserological subset of CFS/FM patients with hypersomnia and cognitive complaints.

 

Source: Nishikai M, Tomomatsu S, Hankins RW, Takagi S, Miyachi K, Kosaka S, Akiya K. Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders. Rheumatology (Oxford). 2001 Jul;40(7):806-10. http://rheumatology.oxfordjournals.org/content/40/7/806.long (Full article)

 

Divided attention deficits in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients and controls were compared on a variety of mood state, personality, and neuropsychological measures, including memory, word finding, and attentional tasks that required participants to focus, sustain, or divide their attention, or to perform a combination of these functions.

CFS patients demonstrated a selective deficit on 3 measures of divided attention. Their performance on the other neuropsychological tests of intelligence, fluency, and memory was no different than that of normal controls despite their reports of generally diminished cognitive capacity. There was an inverse relation between CFS patient fatigue severity and performance on 1 of the divided attention measures.

Given these findings, it is probable that CFS patients will report more cognitive difficulties in real-life situations that cause them to divide their effort or rapidly reallocate cognitive resources between 2 response channels (vision and audition).

 

Source: Ross S, Fantie B, Straus SF, Grafman J. Divided attention deficits in patients with chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):4-11. http://www.ncbi.nlm.nih.gov/pubmed/11388122

 

Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression

Abstract:

Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability.

A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls.

After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.

 

Source: Daly E, Komaroff AL, Bloomingdale K, Wilson S, Albert MS. Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol. 2001;8(1):12-22. http://www.ncbi.nlm.nih.gov/pubmed/11388119