The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome

The relationship of sleep complaints to mood, fatigue, disability, and lifestyle was examined in 69 chronic fatigue syndrome (CFS) patients without psychiatric disorder, 58 CFS patients with psychiatric disorder, 38 psychiatric out-patients with chronic depressive disorders, and 45 healthy controls. The groups were matched for age and gender. There were few differences between the prevalence or nature of sleep complaints of CFS patients with or without current DSM-IIIR depression, anxiety or somatization disorder. CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients. Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong association between relapse and sleep disturbance. Certain types of sleep disorder were associated with increased disability or fatigue in CFS patients. Disrupted sleep appears to complicate the course of CFS. For the most part, sleep complaints are either attributable to the lifestyle of CFS patients or seem inherent to the underlying condition of CFS. They are generally unrelated to depression or anxiety in CFS.     

Speed of improvement in sleep disturbance and anxiety compared with core mood symptoms during acute treatment of depression in old age.

OBJECTIVES: The objective of this study was to examine the relative speed of improvement in sleep disturbance and anxiety symptoms compared with core mood symptoms in acute treatment of late-life major depression. METHOD: The authors conducted secondary analysis of acute treatment data in 470 older patients treated in three federally funded studies. The authors compared rates of improvement in three Hamilton Rating Scale for Depression symptom clusters after stratification by study. RESULTS: Anxiety symptoms improved more slowly with antidepressant monotherapy and with combined pharmacotherapy/psychotherapy, whereas sleep symptoms improved at a similar rate as core mood symptoms. CONCLUSIONS: Anxiety symptoms tend to persist in patients with late-life depression.     

Fatigue in obstructive sleep apnea: driven by depressive symptoms instead of apnea severity?

OBJECTIVE: Obstructive sleep apnea is a common and frequently devastating illness that often includes significant fatigue. Fatigue is also a hallmark depressive symptom. The authors wondered if depressive symptoms in patients with obstructive sleep apnea would account for some of the fatigue beyond that explained by obstructive sleep apnea severity. METHOD: Sixty patients with obstructive sleep apnea-i.e., score >/=15 on the respiratory disturbance index (mean score=49; range=15-111)-underwent polysomnography and completed the Center for Epidemiological Studies Depression Scale (CES-D Scale), Profile of Mood States (POMS), and Medical Outcomes Study surveys. Data were analyzed by using hierarchical regression, with POMS fatigue score as the dependent variable (step 1, forced entry of apnea severity variables; step 2, forced entry of CES-D Scale score). RESULTS: Whereas score on the respiratory disturbance index and the percent of time oxygen saturation was <90% together accounted for 4.2% of variance in scores on the POMS fatigue scale, the CES-D Scale score accounted for 10 times the variance (i.e., an additional 42.3%) in POMS fatigue scale score. CONCLUSIONS: After obstructive sleep apnea severity was controlled, higher levels of depressive symptoms were dramatically and independently associated with greater levels of fatigue. Assessment and treatment of mood symptoms-not just treatment of the disordered breathing itself-might reduce the fatigue experienced by patients with obstructive sleep apnea.     

Core symptoms of major depressive disorder: relevance to diagnosis and treatment

The construct of major depressive disorder makes no etiological assumptions about populations with diverse symptom clusters. "Depressed mood" and "loss of interest or pleasure in nearly all activities" are core features of major depressive episode, though a strong case can be made to pay increasing attention to symptoms of fatigue, sleep disturbance, anxiety, and neurocognitive and sexual dysfunction in the diagnosis and evaluation of treatment outcome. Mood, guilt, work, and interest, as well as psychic anxiety, are consistently identified across validated subscales of the Hamilton Depression Rating Scale as prevalent and sensitive to change with existing treatments. A major limitation of these antidepressant therapies is their narrow spectrum of action. While the core "mood and interest" symptoms have been the main focus of attention, the associated symptoms listed above are often unaffected or exacerbated by current treatments. Careful clinical evaluation should address all of these dimensions, recognizing that improvement may occur sooner in some symptoms (eg, mood) compared with others (eg, sleep disturbance).     

Differential effects of nefazodone and cognitive behavioral analysis system of psychotherapy on insomnia associated with chronic forms of major depression

BACKGROUND: The antidepressant nefazodone and the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) were recently found to have significant, additive effects in a large multicenter study of chronic forms of major depression. As nefazodone-mediated blockade of serotonin-2 receptors may directly relieve insomnia associated with depression, we examined the more specific effects of CBASP and nefazodone, singly and in combination, on sleep disturbances. METHOD: A total of 597 chronically depressed outpatients (DSM-III-R criteria) with at least 1 insomnia symptom were randomly assigned to 12 weeks of treatment with nefazodone (mean final dose = 466 mg/day), CBASP (mean = 16.0 sessions), or the combination (mean dose = 460 mg/day plus a mean of 16.2 CBASP sessions). Continuous and categorical insomnia outcomes, derived from standard clinician- and self-rated assessments, were compared. RESULTS: Patients receiving nefazodone (either alone or in combination with CBASP) obtained significantly more rapid and greater ultimate improvement in insomnia ratings when compared with those treated with CBASP alone. This difference was maximal by the fourth week of therapy and sustained thereafter. Combined treatment did not result in markedly better insomnia scores than treatment with nefazodone alone on most measures, although patients receiving both CBASP and nefazodone were significantly more likely (p < .001) to achieve > or = 50% decrease in insomnia severity. CONCLUSION: Despite comparable antidepressant efficacy, monotherapy with nefazodone or CBASP resulted in markedly different effects on the magnitude and temporal course of insomnia symptoms associated with chronic forms of major depression. Patients receiving the combination of psychotherapy and pharmacotherapy benefited from both the larger and more rapid improvements in insomnia associated with nefazodone therapy and the later-emerging effects of CBASP on the overall depressive syndrome.     

Non-REM sleep EEG power distribution in fatigue and sleepiness

Objectives

The aim of this study is to contribute to the sleep-related differentiation between daytime fatigue and sleepiness.

Methods

135 subjects presenting with sleep apnea–hypopnea syndrome (SAHS, n = 58) or chronic fatigue syndrome (CFS, n = 52) with respective sleepiness or fatigue complaints and a control group (n = 25) underwent polysomnography and psychometric assessments for fatigue, sleepiness, affective symptoms and perceived sleep quality. Sleep EEG spectral analysis for ultra slow, delta, theta, alpha, sigma and beta power bands was performed on frontal, central and occipital derivations.

Results

Patient groups presented with impaired subjective sleep quality and higher affective symptom intensity. CFS patients presented with highest fatigue and SAHS patients with highest sleepiness levels. All groups showed similar total sleep time. Subject groups mainly differed in sleep efficiency, wake after sleep onset, duration of light sleep (N1, N2) and slow wave sleep, as well as in sleep fragmentation and respiratory disturbance. Relative non-REM sleep power spectra distributions suggest a pattern of power exchange in higher frequency bands at the expense of central ultra slow power in CFS patients during all non-REM stages. In SAHS patients, however, we found an opposite pattern at occipital sites during N1 and N2.

Conclusions

Slow wave activity presents as a crossroad of fatigue and sleepiness with, however, different spectral power band distributions during non-REM sleep. The homeostatic function of sleep might be compromised in CFS patients and could explain why, in contrast to sleepiness, fatigue does not resolve with sleep in these patients. The present findings thus contribute to the differentiation of both phenomena.     

Symptom clusters as predictors of late response to antidepressant treatment

OBJECTIVE: While there is some indication from studies in the acute phase of antidepressant treatment that there are differences in the timing of improvement in symptoms, relatively little work has explored the patterns of change for specific symptom clusters and the predictability of these changes to signal eventual response during the acute phase of treatment. This article investigates the use of clusters of symptoms on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) to define the pattern of late response versus nonresponse to antidepressant medication. METHOD: Using principal component analysis, the HAM-D-17 was divided into 4 symptom clusters (mood, sleep/psychic anxiety, appetite, and somatic anxiety/weight). Data for 996 patients with major depressive disorder (DSM-III-R criteria), who participated in a 12-week acute phase study with nefazodone, were subjected to a post hoc analysis of changes in symptom cluster scores. Patients were divided into 3 groups: early responders (< 4 weeks), late responders (4-12 weeks), and nonresponders (> 12 weeks) as defined by < 50% reduction in HAM-D-17 scores from baseline. The late-responder and nonresponder groups were subjected to the principal component analysis. Data were collected from October 1992 to November 1994. RESULTS: There were significant differences in the pattern of symptom change on the mood cluster (weeks 3-4) (p < .0001), the sleep/psychic anxiety cluster (weeks 3-4) (p < .003), and the somatic anxiety/weight cluster (weeks 3-4) (p < .01) for the late responders compared to the nonresponders. Using change scores, a discriminant function analysis correctly assigned 127 of the 182 late responders and 85 of the 133 nonresponders, or 70% of the late responders and 64% of the nonresponders, to their final response groups. CONCLUSION: Monitoring changes in symptom clusters from the HAM-D-17 during this crucial early stage (first 4 weeks) can be used to distinguish late responders (after week 4) from nonresponders. Successful identification of nonresponders based on symptom cluster change in the first 4 weeks would facilitate a shortening of an ineffective treatment trial and allow for necessary changes in treatment strategy, helping physicians more closely follow treatment guidelines.     

Use of slow-release melatonin in treatment-resistant depression

OBJECTIVE: To examine antidepressant augmentation with and hypnotic effects of slow-release melatonin (SR-melatonin) in patients with treatment-resistant depression. DESIGN: Open-label trial. SETTING: Tertiary care outpatient depression clinic. PATIENTS: Nine outpatients who had failed to respond to 2 or more 8-week trials of antidepressant medication. INTERVENTIONS: Patients received SR-melatonin 5 mg per day for the first 2 weeks and 10 mg per day for the final 2 weeks, in addition to their antidepressant medication. OUTCOME MEASURES: Structured Clinical Interview for DSM-IV, Axis 1 Disorders, Hamilton Rating Scale for Depression (HRSD), Beck Depression Inventory, Response Style Questionnaire, sleep and fatigue measures. RESULTS: One patient was excluded after 1 week because of the development of a mixed affective state. In the remaining 8 patients there was a 20% mean decrease in HRSD scores after 4 weeks of treatment, with no individual achieving an improvement of 50% or more. There was a 36% decrease on the 3-item HRSD related to insomnia, with 4 of 8 patients showing at least a 50% improvement on this measure. The greatest decrease in insomnia occurred during the last 2 weeks of the study, following the increase in dosage to 10 mg per day of SR-melatonin. Patients also reported significantly lower levels of fatigue post-treatment. CONCLUSIONS: SR-melatonin may be a useful adjunct for sleep, but does not substantially augment existing antidepressant therapies in some patients with treatment-resistant depression.     

Monozygotic twins discordant for chronic fatigue syndrome: objective measures of sleep

PURPOSE: Chronic fatigue syndrome (CFS) is characterized by profound fatigue accompanied by disturbances of sleep, cognition, mood, and other symptoms. Our objective was to describe sleep architecture in CFS-discordant twin pairs. METHODS: We conducted a co-twin control study of 22 pairs of monozygotic twins where one twin met criteria for CFS and the co-twin was healthy. Twins underwent two nights of polysomnography. RESULTS: The percentage of Stage 3 and REM sleep was greater among the CFS twins than their healthy co-twins (P< or = .05 for both), but no other differences in sleep architecture including sleep latency, REM latency, and total sleep time were observed. Compared to their co-twins, CFS twins had higher values for the apnea-hypopnea index and apnea-hypopnea arousal index (P< or =.05 for both). CONCLUSION: These results do not provide strong evidence for a major role for abnormalities in sleep architecture in CFS. Respiration appears impaired in CFS, but these clinical abnormalities cannot alone account for the prominence of sleep complaints in this illness. The co-twin control methodology highlights the importance of selecting well-matched control subjects.     

Adolescent depression: a placebo-controlled fluoxetine treatment study and follow-up

Forty patients aged 13 to 18 years participated in a placebo-controlled double-blind study of fluoxetine. Fifteen subjects in each group completed the eight week study. Approximately two-thirds of the patients showed marked or moderate clinical global improvement with both fluoxetine and placebo. Fluoxetine was superior to placebo on all clinical measures except for sleep disorder, but the differences were not statistically significant. Thirty-two of the patients and their parents were interviewed after a mean follow-up interval of 24 months (range: 8-46 months). Mean age at follow-up was 18 years (range: 15-22 years). Both groups had shown further improvement at follow-up but there were no significant group differences. Independent of the study, 19 patients (59%) had received intervening treatment following study termination and nine patients (28%) were still in treatment. Adolescent depression appears to respond to treatment but both mood disturbance and psychosocial adaptation problems persist, requiring active follow-through.     

Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome

Objective

To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS).

Methods

Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography + multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders.

Results

Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8 years (SD 10.3)].A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease.In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder.

Conclusions

A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care.     

Predictors of cognitive and physical fatigue in post-acute mild–moderate traumatic brain injury

ABSTRACT

Post-traumatic fatigue (PTF) is a common, disabling, and often chronic symptom following traumatic brain injury (TBI). Yet, the impact of chronic cognitive and physical fatigue and their associations with psychiatric, sleep, cognitive, and psychosocial sequelae in mild–moderate TBI remain poorly understood. Sixty Veterans with a history of mild–moderate TBI and 40 Veteran controls (VC) were administered the Modified Fatigue Impact Scale, a validated measure of TBI-related cognitive and physical fatigue as well as measures of neuropsychiatric, psychosocial, sleep, and objective cognitive functioning. Compared to VC, TBI Veterans endorsed significantly greater levels of cognitive and physical fatigue. In TBI, psychiatric symptoms, sleep disturbance, and post-traumatic amnesia (PTA) were associated with both cognitive and physical fatigue, while loss of consciousness (LOC) and poor attention/processing speed were related to elevations in cognitive fatigue only. In regression analyses, anxiety, sleep disturbance, and LOC significantly predicted cognitive fatigue, while only post-traumatic stress symptoms and PTA contributed to physical fatigue. Cognitive and physical fatigue are problematic symptoms following mild–moderate TBI that are differentially associated with specific injury and psychiatric sequelae. Findings provide potential symptom targets for interventions aimed at ameliorating fatigue, and further underscore the importance of assessing and treating fatigue as a multi-dimensional symptom following TBI.     

Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders

Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pacemaker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for analyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major psychiatric conditions such as chronic schizophrenia. In a good proportion of patients with depression, mood often improves over the course of the day; an extension of waking often has an antidepressant effect. Sleep deprivation has been described as a treatment for depression for more than 30 years, and approximately 50% to 60% of patients with depression respond to this approach, especially those patients who report that their mood improves over the course of the day. The mechanisms by which sleep deprivation exerts its antidepressant effects are still controversial, but a reduction in rapid eye movement sleep (REM sleep), sleep pressure and slow-wave sleep (SWS), or a circadian phase disturbance, have been proposed. Although several studies support each of these hypotheses, none is sufficient to explain all observations reported to date. Unfortunately, the disturbed sleep-wake cycle or behavioural activities of depressed patients often explain several of the abnormalities reported in the diurnal rhythms of these patients. Thus, protocols that specifically manipulate the sleep-wake cycle to unmask the expression of the endogenous circadian pacemaker are greatly needed. In chronic schizophrenia, significant disturbances in sleep continuity, REM sleep, and SWS have been consistently reported. These disturbances are different from those observed in depression, especially with regard to REM sleep. Circadian phase abnormalities in schizophrenic patients have also been reported. Future research is expected to clarify the nature of these abnormalities.     

Non-recognition of depression and other non-motor symptoms in Parkinson's disease

BACKGROUND: Depression, anxiety, fatigue and sleep disorders occur commonly in patients with Parkinson's disease (PD). These non-motor symptoms often contribute to the reduction of functional abilities in PD patients. OBJECTIVE: This study was designed to evaluate the diagnostic accuracy of the treating neurologist for a variety of behavioral symptoms commonly associated with PD. METHODS: A prospective evaluation of 101 patients with PD selected in no particular order was conducted. All patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr Stage (H/Y), and the Schwab & England Scale (S/E). The patients completed a brief screening questionnaire for depression and anxiety followed by the administration of a battery of standardized tests including the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Fatigue Severity Scale (FSS), and the Pittsburgh Sleep Quality Inventory (PSQI). RESULTS: Standardized testing showed evidence of a problem with depression in 44% of patients, anxiety in 39%, fatigue in 42% and sleep disturbance in 43%. The prevalence of these conditions, identified by the treating neurologist was lower: 21% with depression, 19% with anxiety, 14% with fatigue and 39% with sleep disturbance. The diagnostic accuracy for the treating neurologists was 35% for depression, 42% for anxiety, 25% for fatigue, and 60% for sleep disturbance. CONCLUSION: This study demonstrates that during routine office visits, neurologists failed to identify the presence of depression, anxiety, and fatigue more than half of the time and failed to recognize sleep disturbance in 40% of patients. Awareness of the likelihood of underrecognition of behavioral symptoms in PD should generate approaches to improve diagnostic accuracy and facilitate timely therapeutic interventions.     

Nefazodone in primary insomnia: an open pilot study

The present study is the first to investigate the effect of the antidepressant nefazodone on sleep in patients with primary (psychophysiological) insomnia. Following baseline assessment of sleep (polysomnography and subjective sleep parameters), 32 patients received initially 100 mg nefazodone in a single dose at bedtime; according to efficacy and tolerability, the dose could be increased up to 400 mg. Polysomnography and assessment of subjective sleep parameters were repeated after 4 weeks' administration. 12 patients dropped out, 11 of them due to lack of efficiency or intolerable side effects. In 20 patients who completed, the authors observed a lengthened sleep onset latency, decreases in stage 1 and slow wave sleep, and increases in stages 2 and REM under nefazodone. Subjective measures of sleep mirrored a clearer improvement: there was a significant reduction of the PSQI total score and all subscores except sleep latency. We suppose that the dose range chosen was too high for this patient population, thus accounting for the high proportion of dropouts and the partly unfavorable effects on objective sleep parameters. For a definite evaluation of the possible role of nefazodone in the treatment of primary (psychophysiological) insomnia, double-blind, placebo-controlled, randomized studies with lower doses are needed.     

Are depressive symptoms nonspecific in patients with acute stroke?

OBJECTIVE: Some investigators have suggested that major depression might be overdiagnosed in stroke patients because of changes in appetite, sleep, or sexual interest caused by their medical illness; others have suggested that depression may be underdiagnosed in stroke patients who deny symptoms of depression because of anosognosia, neglect, or aprosody. The authors' goal was to determine how frequently depressive symptoms occur in acute stroke patients with and without depressed mood to estimate how often diagnostic errors of inclusion or exclusion may be made. METHOD: They examined the rate of autonomic and psychological symptoms of depression in 205 patients who were consecutively hospitalized for acute stroke. Eighty-five (41%) of these patients had depressed mood, and 120 (59%) had no mood disturbance. Forty-six (54%) of the 85 patients with depressed mood (22% of all patients) were assigned the DSM-III diagnosis of major depression. RESULTS: The 120 patients without mood disturbance had a mean of one autonomic symptom, but the 85 patients with depressed mood had a mean of almost four. Tightening the diagnostic criteria to account for one more nonspecific autonomic symptom decreased the number of patients with major depression by only three; adding two more criteria decreased the number by only five. Thus, the rate of DSM-III major depression was 1% higher than the rate with one extra nonspecific autonomic symptom and 2% higher than the rate with two extra criteria. Conversely, loosening diagnostic criteria to account for denial of depressive illness increased the rate of major depression by only 5%. CONCLUSIONS: Both autonomic and psychological depressive symptoms are strongly associated with depressed mood in acute stroke patients.     

The effects of repeated thermal therapy for two patients with chronic fatigue syndrome

OBJECTIVE: This paper describes the successful treatment of two patients with chronic fatigue syndrome (CFS) using repeated thermal therapy. METHODS: Two patients with CFS underwent treatment with prednisolone (PSL), with no satisfactory effect. They were subjected to thermal therapy that consisted of a far-infrared ray dry sauna at 60 degrees C and postsauna warming. The therapy was performed once a day, for a total of 35 sessions. After discharge, these subjects continued the therapy once or twice a week on an outpatient basis for 1 year. RESULTS: Symptoms such as fatigue, pain, sleep disturbance, and low-grade fever were dramatically improved after 15 to 25 sessions of thermal therapy. Although PSL administration was discontinued, the subjects showed no relapse or exacerbation of symptoms during the first year after discharge. The patients became socially rehabilitated 6 months after discharge. CONCLUSIONS: These results suggest that repeated thermal therapy might be a promising method for the treatment of CFS.     

Objective assessment of personality disorder in chronic fatigue syndrome

OBJECTIVES: This study aims to objectively assess the prevalence and nature of personality disorders in depressed and nondepressed chronic fatigue syndrome (CFS) patients and compare this to depressed and healthy control groups. METHODS: Sixty-one patients attending a tertiary referral clinic with chronic fatigue syndrome, 40 psychiatric inpatients with depressive disorder and 45 healthy medical students completed the Structured Clinical Interview for DSM-III-R Diagnoses (SCID-II) in addition to providing routine clinical and demographic information. RESULTS: Thirty-nine percent of the CFS group, 73% of the depressed group and 4% of the healthy group were diagnosed with personality disorders. Cluster C disorders were the most common in both the CFS and depressed group. The depressed CFS patients had more Cluster B personality disorders than nondepressed CFS patients. Overall for CFS patients there was no association between mood state and personality disorder. CONCLUSIONS: High levels of personality disorder are found on objective assessment of CFS patients attending a teaching hospital clinic. This cannot be accounted for by comorbid depression.     

Psychological correlates of functional status in chronic fatigue syndrome

Background: The present study was designed to test a cognitive model of impairment in chronic fatigue syndrome (CFS) in which disability is a function of severity of fatigue and depressive symptoms, generalized somatic symptom attributions and generalized illness worry. Methods: We compared 45 CFS and 40 multiple sclerosis (MS) outpatients on measures of functional ability, fatigue severity, depressive symptoms, somatic symptom attribution and illness worry. Results: The results confirmed previous findings of lower levels of functional status and greater fatigue among CFS patients compared to a group of patients with MS. Fatigue severity was found to be a significant predictor of physical functioning but not of psychosocial functioning in both groups. In CFS, when level of fatigue was controlled, making more somatic attributions was associated with worse physical functioning, and both illness worry and depressive symptoms were associated with worse psychosocial functioning. Conclusions: Our findings support the role of depression and illness cognitions in disability in CFS sufferers. Different cognitive factors account for physical and psychosocial disability in CFS and MS. The SF-36 may be sensitive to symptom attributions, suggesting caution in its interpretation when used with patients with ill-defined medical conditions.