Impaired associative learning in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report cognitive difficulties (impaired attention, memory and reasoning). Neuropsychological tests have failed to consistently find cognitive impairments to the degree reported by CFS patients.

We tested patients with CFS and sedentary controls in protocols designed to measure sensory reactivity and acquisition of the classically conditioned eyeblink response. Patients with CFS exhibited normal sensitivity and responsivity to acoustic stimuli.

However, CFS patients displayed impaired acquisition of the eyeblink response using a delayed-type conditioning paradigm. Sensitivity and responsivity to the airpuff stimulus were normal.

In the absence of sensory/motor abnormalities, impaired acquisition of the classically conditioned eyeblink response indicates an associative deficit. These data suggest organic brain dysfunction within a defined neural substrate in CFS patients.

 

Source: Servatius RJ, Tapp WN, Bergen MT, Pollet CA, Drastal SD, Tiersky LA, Desai P, Natelson BH. Impaired associative learning in chronic fatigue syndrome. Neuroreport. 1998 Apr 20;9(6):1153-7. http://www.ncbi.nlm.nih.gov/pubmed/9601685

 

Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome

Abstract:

AIM: To perform a clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS) where patients were told they would receive placebo or active agent at different times during the 6-week trial. We chose selegiline, a specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of lowdose phenelzine, a nonspecific MAO inhibitor, showed a small but significant therapeutic effect.

METHODS: Questionnaires comprised of 19 tests of mood, fatigue, functional status and symptom severity were collected at the start and end of the trial as well as 2 weeks after its start. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg tablet of agent was given twice a day. The plan was to compare the changes in the 19 tests during the placebo phase to those found in the active treatment phase in 19 patients completing the trial.

FINDINGS: Significant improvement in 3 variables-tension/anxiety, vigor and sexual relations-was found. A significant pattern of improvement compared to worsening was found for the 19 self-report vehicles during active treatment as compared with placebo treatment. Evidence for an antidepressant effect of the drug was not found.

CONCLUSIONS: Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect.

 

Source: Natelson BH, Cheu J, Hill N, Bergen M, Korn L, Denny T, Dahl K. Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome. Neuropsychobiology. 1998;37(3):150-4. http://www.ncbi.nlm.nih.gov/pubmed/9597672

 

Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome, and determine whether the relation is independent of psychiatric factors.

METHODS: The subjects were 53 patients with chronic fatigue syndrome and 32 healthy controls who did not exercise regularly. Subjects were administered a structured psychiatric interview and completed questionnaires focusing on depression and functional disability. They also completed a battery of standardised neuropsychological tasks focusing on the cognitive domains that patients with chronic fatigue syndrome experience as particularly difficult: memory (verbal and visual), and attention/concentration. A test score was defined as failing when it was > or =2 SD below the mean of the healthy controls after controlling for demographic factors.

RESULTS: Those patients with chronic fatigue syndrome with higher numbers of failing neuropsychological test scores reported significantly more days of general inactivity in the past month than those with fewer failing scores. This result remained significant even after partialling out the contribution of the presence of a comorbid axis I psychiatric episode and the overall level of depressive symptomology. Patients with failing verbal memory scores were particularly functionally disabled compared with those with passing scores.

CONCLUSION: A relation was found between cognitive impairment and functional disability which could not be explained entirely on the basis of psychiatric factors.

Comment in: The importance of mental fatigue. [J Neurol Neurosurg Psychiatry. 1998]

 

Source: Christodoulou C, DeLuca J, Lange G, Johnson SK, Sisto SA, Korn L, Natelson BH. Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):431-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170049/

 

Neuropsychology of chronic fatigue syndrome: a critical review

Abstract:

This article provides a comprehensive and critical review of the neuropsychological and related literature on chronic fatigue syndrome (CFS). Despite the methodological limitations observed in several studies, some consistent findings are noted.

The most consistently documented neuropsychological impairments are in the areas of complex information processing speed and efficiency. General intellectual abilities and higher order cognitive skills are intact. Emotional factors influence subjective report of cognitive difficulty, whereas their effect on objective performance remains uncertain.

Although the neuropathological processes underlying cognitive dysfunction in CFS are not yet known, preliminary evidence suggests the involvement of cerebral white matter. Directions for future research are outlined.

 

Source: Tiersky LA, Johnson SK, Lange G, Natelson BH, DeLuca J. Neuropsychology of chronic fatigue syndrome: a critical review. J Clin Exp Neuropsychol. 1997 Aug;19(4):560-86. http://www.ncbi.nlm.nih.gov/pubmed/9342690

 

Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease

Abstract:

OBJECTIVE: To examine the effect of the presence or absence of psychiatric disease on cognitive functioning in chronic fatigue syndrome.

METHODS: Thirty six patients with chronic fatigue syndrome and 31 healthy controls who did not exercise regularly were studied. Subgroups within the chronic fatigue syndrome sample were formed based on the presence or absence of comorbid axis I psychiatric disorders. Patients with psychiatric disorders preceding the onset chronic fatigue syndrome were excluded. Subjects were administered a battery of standardised neuropsychological tests as well as a structured psychiatric interview.

RESULTS: Patients with chronic fatigue syndrome without psychiatric comorbidity were impaired relative to controls and patients with chronic fatigue syndrome with concurrent psychiatric disease on tests of memory, attention, and information processing.

CONCLUSION: Impaired cognition in chronic fatigue syndrome cannot be explained solely by the presence of a psychiatric condition.

 

Source: DeLuca J, Johnson SK, Ellis SP, Natelson BH. Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease. J Neurol Neurosurg Psychiatry. 1997 Feb;62(2):151-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC486726/ (Full article)

 

The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression

Abstract:

The effects of fatigue on neuropsychological performance were examined in patients with fatiguing illnesses. Repeated testing with the Paced Auditory Serial Addition Test (PASAT; Gronwall, 1977) was employed over the course of a demanding neuropsychological testing session. It was hypothesized that if fatigue affects performance, one would expect to observe “blunting” of the PASAT practice effect.

Fifteen of the study participants live with chronic fatigue syndrome (CFS), 15 with multiple sclerosis (MS), 14 with depression (DEP), and 15 are healthy, sedentary controls. Overall PASAT performance was significantly reduced for CFS and DEP participants compared to controls, whereas mean performance did not differ across the three fatiguing illness groups. Degree of improvement across trials (i.e., practice effect) for the groups did not differ from controls’. Neither subjective fatigue or DEP were significantly related to PASAT performance.

These findings suggest that fatigue does not universally impair performance during neuropsychological assessment even in groups in which fatigue is a prominent symptom.

 

Source: Johnson SK, Lange G, DeLuca J, Korn LR, Natelson B. The effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol. 1997;4(3):145-53. http://www.ncbi.nlm.nih.gov/pubmed/16318477

 

Sudden vs gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures

Abstract:

To examine the influence of mode of illness onset on psychiatric status and neuropsychological performance, 36 patients with CFS were divided into two groups: sudden vs gradual onset of symptoms.

These two CFS subgroups were compared to each other and to sedentary healthy controls on standardized neuropsychological tests of attention/concentration, information processing efficiency, memory, and higher cortical functions. In addition, the distribution of comorbid Axis I psychiatric disease between the two CFS groups was examined.

The rate of concurrent psychiatric disease was significantly greater in the CFS-gradual group relative to the CFS-sudden group. While both CFS groups showed a significant reduction in information processing ability relative to controls, impairment in memory was more severe in the CFS-sudden group. Because of the significant heterogeneity of the CFS population, the need for subgroup analysis is discussed.

 

Source: DeLuca J, Johnson SK, Ellis SP, Natelson BH. Sudden vs gradual onset of chronic fatigue syndrome differentiates individuals on cognitive and psychiatric measures. J Psychiatr Res. 1997 Jan-Feb;31(1):83-90. http://www.ncbi.nlm.nih.gov/pubmed/9201650

 

Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if patients with the chronic fatigue syndrome have less vagal power during walking and rest periods following walking, in comparison to a group of healthy controls.

Eleven patients (ten women and one man) who fulfilled the case definition for chronic fatigue syndrome modified to reduce heterogeneity and eleven healthy, but sedentary, age- and sex-matched controls walked on a treadmill at 2.5 mph four times each for 4 min duration. Between each period of walking, subjects were given a 4-min seated rest period. Vagal power, a Fourier-based measure of cardiac, parasympathetic activity in the frequency range of 0.15 to 1.0 Hz, was computed.

In each period of walking and in one period of rest, patients had significantly less vagal power than the control subjects despite there being no significant group-wise differences in mean heart rate, tidal volume, minute volume, respiratory rate, oxygen consumption or total spectrum power. Further, patients had a significant decline in resting vagal power after periods of walking.

These results suggest a subtle abnormality in vagal activity to the heart in patients with the chronic fatigue syndrome and may explain, in part, their post-exertional symptom exacerbation.

 

Source: Cordero DL, Sisto SA, Tapp WN, LaManca JJ, Pareja JG, Natelson BH. Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome. Clin Auton Res. 1996 Dec;6(6):329-33. http://www.ncbi.nlm.nih.gov/pubmed/8985621

 

Selective impairment of auditory processing in chronic fatigue syndrome: a comparison with multiple sclerosis and healthy controls

Abstract:

The most consistent deficit observed in individuals with Chronic Fatigue Syndrome has been in efficiency of information processing. To examine the possibility of a modality-specific impairment, the present study examined subjects with Chronic Fatigue Syndrome, multiple sclerosis, and healthy controls on an auditory-versus visual-paced serial-addition test. 20 subjects with Chronic Fatigue Syndrome, 20 subjects with clinically definite Multiple Sclerosis, and 20 sedentary healthy controls were compared.

One-half of the subjects in each group were administered the Paced Auditory Serial Addition Test and the other half were administered the Paced Visual Serial Addition Test. The group with Chronic Fatigue Syndrome was differentially impaired on the auditory relative to the visual processing task. The group with Multiple Sclerosis was equally impaired on both versions of the task. The results are discussed within the framework of Baddeley’s model of working memory.

 

Source: Johnson SK, DeLuca J, Diamond BJ, Natelson BH. Selective impairment of auditory processing in chronic fatigue syndrome: a comparison with multiple sclerosis and healthy controls. Percept Mot Skills. 1996 Aug;83(1):51-62. http://www.ncbi.nlm.nih.gov/pubmed/8873173

 

Depression in fatiguing illness: comparing patients with chronic fatigue syndrome, multiple sclerosis and depression

Abstract:

Because depression is commonly observed in the chronic fatigue syndrome (CFS), the present study sought to determine whether the symptom pattern is similar to that seen in clinically depressed subjects (DEP). Individuals with multiple sclerosis (MS) were chosen as an additional comparison group because MS is a fatiguing illness of known organic etiology. The Beck Depression Inventory (BDI) was used to compare categories of depressive symptomatology.

Absolute scores on the BDI were higher for the depressed group on mood and self-reproach symptoms, but were not higher than the CFS group on somatic and vegetative items. Analysis of symptoms as a percentage of total BDI score revealed no significant differences in mood or vegetative items among the three groups. The CFS and MS groups exhibited a significantly lower percentage of self-reproach symptoms than DEP, whereas the DEP group showed a lower percentage of somatic symptoms than the CFS and MS groups.

 

Source: Johnson SK, DeLuca J, Natelson BH. Depression in fatiguing illness: comparing patients with chronic fatigue syndrome, multiple sclerosis and depression. J Affect Disord. 1996 Jun 20;39(1):21-30. http://www.ncbi.nlm.nih.gov/pubmed/8835650