Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG) frequencies in monozygotic twins discordant for chronic fatigue syndrome.

METHODS: Thirteen pairs of female twins underwent polysomnography. During the first night, they adapted to the sleep laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was conducted on sleep electroencephalographic records according to standard criteria, and power spectral analysis was used to quantify delta through beta frequency bands, processed in 6-s blocks. Data were averaged across sleep stage within each twin and coded for sleep stage and the presence or absence of chronic fatigue syndrome (CFS). A completely within-subjects repeated measure multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs.

RESULTS: No significant differences in spectral power in any frequency band were found between those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects genetic influences on the sleep electroencephalogram rather than disease-specific sleep pathology.

CONCLUSIONS: The genetic influences on sleep polysomnography and microarchitecture appear to be stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms that probe sleep regulation may provide a better description of sleep abnormalities in CFS.

 

Source: Armitage R, Landis C, Hoffmann R, Lentz M, Watson N, Goldberg J, Buchwald D. Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome. J Psychosom Res. 2009 Jan;66(1):51-7. doi: 10.1016/j.jpsychores.2008.08.004. Epub 2008 Nov 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634600/ (Full article)

 

Twin analyses of fatigue

Abstract:

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects.

 

Source: Schur E, Afari N, Goldberg J, Buchwald D, Sullivan PF. Twin analyses of fatigue. Twin Res Hum Genet. 2007 Oct;10(5):729-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953372/ (Full article)

 

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

 

The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with altered amounts of slow wave sleep, which could reflect reduced delta electroencephalograph (EEG) activity and impaired sleep regulation. To evaluate this hypothesis, we examined the response to a sleep regulatory challenge in CFS.

DESIGN: The first of 3 consecutive nights of study served as laboratory adaptation. Baseline sleep was assessed on the second night. On the third night, bedtime was delayed by 4 hours, followed by recovery sleep. Total available sleep time was held constant on all nights.

SETTING: A research sleep laboratory.

PARTICIPANTS: 13 pairs of monozygotic twins discordant for CFS.

INTERVENTIONS: N/A.

MEASUREMENTS AND RESULTS: Power spectral analysis quantified slow wave activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2, 3, or 4) on each night. To ensure comparability, analyses were restricted to the first 4 NREM periods on each night. Data were coded for NREM period and twin pair. Repeated-measures analysis of variance (ANOVA) contrasted sleep delay effects across NREM periods between twin pairs. A second ANOVA calculated the SWA in each NREM period in recovery sleep relative to baseline SWA. The 2 groups of twins were similar on baseline SWA power. After sleep delay, CFS twins exhibited significantly less SWA power in the first NREM period of recovery sleep and accumulated a smaller percentage of SWA in the first NREM period than their co-twins.

CONCLUSIONS: CFS is associated with a blunted SWA response to sleep challenge, suggesting that the basic sleep drive and homeostatic response are impaired.

 

Source: Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome, Sleep. 2007 May;30(5):657-62. https://www.ncbi.nlm.nih.gov/pubmed/17552382

 

Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

OBJECTIVE: Individuals with chronic fatigue syndrome (CFS) experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their cotwins without CFS.

DESIGN: Cotwin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS.

PATIENTS AND SETTING: Fifteen monozygotic twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington.

RESULTS: Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their cotwins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain (P = 0.003) and fatigue (P < 0.001) by their cotwins without CFS.

CONCLUSIONS: These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS.

 

Source: Ullrich PM, Afari N, Jacobsen C, Goldberg J, Buchwald D. Cold pressor pain sensitivity in monozygotic twins discordant for chronic fatigue syndrome. Pain Med. 2007 Apr;8(3):216-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957294/ (Full article)

 

Premorbid predictors of chronic fatigue

Abstract:

CONTEXT: Chronic fatigue syndrome is a disabling problem characterized by persistent fatigue lasting at least 6 months with a number of ancillary symptoms. Although the etiology of chronic fatiguing illness is unknown, some evidence suggests that stress may confer increased risk for development of the disorder. Moreover, subjects with chronic fatiguing illness may have distinctive personality traits, although this finding could reflect confounding by other mechanisms.

OBJECTIVE: To assess the prospective association of premorbid self-reported stress and personality with chronic fatigue-like illness.

DESIGN: Prospective nested case-control study in a population-based sample.

SETTING: General community.

PARTICIPANTS: From the Swedish Twin Registry, 19,192 twins born between January 1, 1935, and December 31, 1958.

MAIN OUTCOME MEASURES: Information about current chronic fatiguing illnesses was obtained from computer-assisted telephone interviews conducted between 1998 and 2002. Self-reported stress (based on a single question) and personality scales (emotional instability and extraversion in the Eysenck Personality Inventory) were measured from 1972 to 1973 by a mailed questionnaire. Relative risks were estimated with case-control analyses (matched for age and sex) and co-twin control analyses (comparing discordant pairs).

RESULTS: Higher emotional instability and self-reported stress in the premorbid period were associated with higher risk for chronic fatigue-like illness in matched case-control analyses (odds ratios, 1.72 and 1.64, respectively). In co-twin control analyses, relative risk of emotional instability decreased to 1.02 whereas that of stress increased considerably to 5.81. There was no association between extraversion and fatigue.

CONCLUSIONS: Elevated premorbid stress is a significant risk factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness.

 

Source: Kato K, Sullivan PF, Evengård B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006 Nov;63(11):1267-72. https://www.ncbi.nlm.nih.gov/pubmed/17088507

 

The prevalence of self-reported chronic fatigue in a U.S. twin registry

Abstract:

OBJECTIVE: To investigate the prevalence and correlates of various definitions of self-reported lifetime fatiguing illness in a U.S. twin registry.

METHODS: Data from 4591 female and male twins from the population-based Mid-Atlantic Twin Registry were available for this study. Variables representing different definitions of lifetime fatiguing illness and personal characteristics were obtained through questionnaires. Odds ratios and 95% confidence intervals were calculated as measures of association between fatigue and gender. Kaplan-Meier curves were produced to examine the age at onset for lifetime fatiguing illnesses.

RESULTS: Prevalences for different definitions of self-reported lifetime fatigue ranged from 36.7% for any fatigue to 2.7% for chronic fatigue syndrome-like illness. Females were two to three times more likely to report fatigue than males. Gender differences increased as fatigue definitions grew more restrictive. Ages at onset of chronic fatiguing illness were significantly earlier and the number of ancillary symptoms was greater for females than males. People with lifetime fatigue had significantly more compromised functional status than people without lifetime fatigue.

CONCLUSION: The prevalence of self-reported lifetime fatiguing illness varied widely depending upon how it was defined. Given the debilitating consequences of fatiguing illnesses, the reasons for the female predominance and the earlier onset in women should receive increased research priority.

 

Source: Furberg H, Olarte M, Afari N, Goldberg J, Buchwald D, Sullivan PF. The prevalence of self-reported chronic fatigue in a U.S. twin registry. J Psychosom Res. 2005 Nov;59(5):283-90. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949064/

 

Chronic fatigue in a population sample: definitions and heterogeneity

Abstract:

BACKGROUND: Numerous nosological decisions are made when moving from the common human symptom of unusual fatigue to the rare chronic fatigue syndrome (CFS). These decisions have infrequently been subjected to rigorous evaluation.

METHOD: We obtained telephone interview data on fatiguing symptoms from 31406 individuals twins in the Swedish Twin Registry aged 42-64 years; 5330 subjects who endorsed fatigue and possessed no exclusionary condition formed the analytic group. We evaluated the definition and classification of CFS-like illness using graphical methods, regression models, and latent class analysis.

RESULTS: Our results raise fundamental questions about the 1994 Centers for Disease Control criteria as (1) there was no empirical support for the requirement of four of eight cardinal CFS symptoms; (2) these eight symptoms were not equivalent in their capacity to predict fatigue; and (3) no combination of symptoms was markedly more heritable. Critically, latent class analysis identified a syndrome strongly resembling CFS-like illness.

CONCLUSIONS: Our data are consistent with the ‘existence’ of CFS-like illness although the dominant nosological approach captures population-level variation poorly. We suggest that studying a more parsimonious case definition – impairing chronic fatigue not due to a known cause – would represent a way forward.

 

Source: Sullivan PF, Pedersen NL, Jacks A, Evengård B. Chronic fatigue in a population sample: definitions and heterogeneity. Psychol Med. 2005 Sep;35(9):1337-48. http://www.ncbi.nlm.nih.gov/pubmed/16168156

 

Twin analyses of chronic fatigue in a Swedish national sample

Abstract:

BACKGROUND: Chronic fatigue has infrequently been studied in twins. Data from twin studies can inform clinical and research approaches to the management and etiology of human complex traits.

METHOD: The authors obtained telephone interview data on current chronic fatigue from 31406 individuals twins in the Swedish Twin Registry (aged 42-64 years, 75.68% response rate), from both members of 12407 pairs and from one member of 6592 pairs. Of the complete pairs, 3269 pairs were monozygotic, 9010 pairs dizygotic, and 128 pairs of unknown zygosity. Structural equation twin modeling was used to estimate the latent genetic architecture of varying definitions of fatiguing illness.

RESULTS: Estimates of additive genetic effects, shared environmental effects, and individual-specific environmental effects were similar in males and females. No definition of current fatiguing illness (ranging from any fatigue to CFS-like illness) was strikingly distinctive. Individual-specific effects were the predominant source of variation, followed by modest genetic influences. We could not exclude a small but conceptually important contribution of shared environmental effects.

CONCLUSIONS: Current fatiguing illness appears to be a complex trait resulting from both environmental and genetic sources of variation without pronounced differences by gender.

 

Source: Sullivan PF, Evengård B, Jacks A, Pedersen NL. Twin analyses of chronic fatigue in a Swedish national sample. Psychol Med. 2005 Sep;35(9):1327-36. http://www.ncbi.nlm.nih.gov/pubmed/16168155

 

The epidemiology of chronic fatigue in the Swedish Twin Registry

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity.

METHOD: We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS.

FINDINGS: The 6-month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender.

INTERPRETATION: CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender.

 

Source: Evengård B, Jacks A, Pedersen NL, Sullivan PF. The epidemiology of chronic fatigue in the Swedish Twin Registry. Psychol Med. 2005 Sep;35(9):1317-26. http://www.ncbi.nlm.nih.gov/pubmed/16168154