Chronic fatigue syndrome and neurotransmitters

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic illness characterized by persistent fatigue, which could be caused by a variety of etiologic factors including viral infection, abnormal production of cytokines and abnormal acylcarnitine metabolism. Recent studies suggest that CFS is closely associated with attenuation of central synaptic transmission mediated by neurotransmitters such as serotonin and glutamate. Attenuation of serotonin neurotransmission can be caused by increased expression of serotonin transporter, which results either from viral infection and subsequent production of interferon–alpha or from abnormal promoter for serotonin transporter gene. Other neurotransmitter systems may be also involved in CFS mediated by abnormal acylcarnitine metabolism and autoantibodies for neurotransmitter receptors. In this review, we focus recent data on CFS in terms of neurotransmitters.

 

Source: Miwa S, Takikawa O. Chronic fatigue syndrome and neurotransmitters. Nihon Rinsho. 2007 Jun;65(6):1005-10. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561689

 

Genetic background of chronic fatigue syndrome

Abstract:

Although previous twin and family studies have suggested the involvement of genetic factor(s) in the pathogenesis of chronic fatigue syndrome (CFS), responsible gene for CFS was not known. We have recently reported the association of serotonin transporter gene polymorphism in CFS. A significant increase of longer (L and XL) alleic variants was found in the CFS patients compared to the controls. Compared to S allele, the L allele is believed to retain higher transcriptional activity, which causes decreased concentration of serotonin in the extracellular space, namely, active serotonin in CFS. These results thus support the serotonin hypothesis in the pathogenesis of CFS.

 

Source: Narita M, Narita N. Genetic background of chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):997-1002. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561688

 

Viral infections in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous illness in which patients can have different, overlapping signs and symptoms. No single underlying cause has been established for all CFS patients. Epidemiological studies reveal that a flu-like sickness precedes the onset in the majority of cases. The major hypothesis of the pathogenesis of CFS is that infectious agents such as viruses, may trigger and lead to chronic activation of the immune system with abnormal regulation of cytokine production. Many studies have been performed to identify the possible microbial triggers and to understand the epidemiological microbial agents. We have summarized the recent progressive literature of virus, rickettsia, and mycoplasma implicated in the pathogenesis of CFS.

 

Source: Sairenji T, Nagata K. Viral infections in chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):991-6. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561687

 

Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria

Abstract:

Chronic fatigue syndrome (CFS) is an operational concept proposed by Centers for Disease Control and Prevention to clarify the unknown etiology of the syndrome characterized by the sensation of abnormally prolonged fatigue. Lots of investigators reported various abnormalities such as virus infection, immune abnormalities, HPA axis abnormalities, metabolic abnormalities, etc., but there are a few abnormalities common to vast majority cases of CFS. Therefore, lots of people as well as medical doctors are still skeptical about the presence of CFS.

However, recent studies reveal that CFS can be understood to be a special condition based on the abnormality of neuroendocrine-immunologic system caused by the psycho-social stress and some genetic components. Under these conditions, a reactivation of various kinds of herpes virus infections and/or chronic infections might occur as a result of immune dysfunction, causing the abnormal production of several cytokines. A distinctive feature of CFS is thought to be the secondary brain dysfunction caused by the abnormal production of several cytokines. In this paper, I show the overview of CFS focusing around prevalence, economic impact and diagnostic criteria in Japan.

 

Source: Kuratsune H. Overview of chronic fatigue syndrome focusing on prevalence and diagnostic criteria. Nihon Rinsho. 2007 Jun;65(6):983-90. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561686

 

History of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is not a new disease. Similar morbidities have been known as different names since past several centuries. For example, neurasthenia, epidemic neuromyasthenia, myalgic encephalomyelitis, Akureyri disease, Royal Free disease, chronic EBV disease, post-viral fatigue syndrome etc. Much of the recent interest in CFS was generated by incidence of infection-like outbreak at Lake Tahoe in Nevada. The Center for Disease Control (USA) realized that correlation was poor between those patients who had virologic evidence of EBV infection and those who had the symptoms of chronic fatigue. This is a review of the history of CFS. (1) Historical perspectives in chronic fatigue cases in past old period, (2) Post-viral infectious fatigue and chronic fatigue (myalgic encephalomyelitis), (3) Recent trend of CFS studies and its clinical similar situation. Finally, I would like to state that we intend to draw up a new diagnostic guideline for CFS in Japan.

 

Source: Hashimoto N. History of chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):975-82. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561685

 

How common is chronic fatigue syndrome; how long is a piece of string?

Comment on: Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. [Popul Health Metr. 2007]

One of the most difficult tasks in medicine is to accurately measure how common illnesses are. Why do we do it? Justifications include being able to plan health care and public health priorities, as well as highlighting specific diseases for extra funding for both health care and research. Yet the jobbing physician at the sharp edge of clinical practice cares little about the exact prevalence of a disease or illness, since this is all too obvious from the frequency of the problems presented by patients who come through the door.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904177/

 

Source: White PD. How common is chronic fatigue syndrome; how long is a piece of string? Popul Health Metr. 2007 Jun 8;5:6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904177/ (Full article)

 

Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with no known cause or effective therapy. Population-based epidemiologic data on CFS prevalence are critical to put CFS in a realistic context for public health officials and others responsible for allocating resources.

METHODS: Based on a random-digit dialing survey we ascertained CFS cases and controls to estimate the prevalence of CFS in metropolitan, urban, and rural populations of Georgia. This report focuses on the 5,623 of 19,381 respondents ages 18 to 59 years old. Fatigued (2,438), randomly selected unwell not fatigued (1,429) and randomly selected well (1,756) respondents completed telephone questionnaires concerning fatigue, other symptoms, and medical history. Subsets of those identified by interview as having CFS-like illness (292), chronic unwellness which was not CFS-like (268 – randomly selected), and well subjects (223, matched to those with CFS-like illness on sex, race, and age) completed a clinical evaluation.

RESULTS: We estimated that 2.54% of persons 18 to 59 years of age suffered from CFS. There were no significant differences in prevalence of CFS between metropolitan, urban or rural populations or between white and black residents of the three regions. However, there were significant differences in female-to-male ratios of prevalence across the strata (metropolitan female: male 11.2 : 1, urban 1.7 : 1, rural 0.8 : 1).

CONCLUSION: We estimated that 2.54% of the Georgia population suffers from CFS, which is 6- to 10-fold higher than previous population-based estimates in other geographic areas. These differences may reflect broader screening criteria and differences in the application of the case definition. However, we cannot exclude the possibility that CFS prevalence may be higher in Georgia than other areas where it has been measured. Although the study did not identify differences in overall prevalence between metropolitan, urban, and rural Georgia populations, it did suggest the need for additional stratified analyses by geographic strata.

Comment in: How common is chronic fatigue syndrome; how long is a piece of string? [Popul Health Metr. 2007]

 

Source: Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904178/ (Full article)

 

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

 

Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents

Abstract:

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants’ characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.

 

Source: ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM, Schedlowski M, Heijnen CJ. Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents.Brain Behav Immun. 2007 Nov;21(8):1063-74. Epub 2007 Jun 1. https://www.ncbi.nlm.nih.gov/pubmed/17544255

The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study

Abstract:

Cancer-related fatigue (CRF) is a common and disabling symptom complex reported by survivors. This study aimed to better understand the manifestations of CRF in women treated for breast cancer, and to compare them with those of women diagnosed with chronic fatigue syndrome (CFS).

Women with CRF persisting 6 months after treatment for early stage breast cancer, and women with CFS participated in separate, audiotaped focus groups. Transcripts of the sessions were analyzed using the NUD*IST software, and interpreted using grounded theory. Twenty-eight women participated, 16 with CRF and 12 with CFS. Analysis of transcripts from both groups revealed a similar core set of symptoms, featuring fatigue, neurocognitive difficulties, and mood disturbances.

Women with CFS reported additional symptoms including musculoskeletal pain and influenza-like manifestations. Both groups suffered disabling behavioral consequences of the symptom complex. Qualitatively, CRF appears closely related to CFS. These findings raise the emergent hypothesis of a conserved neurobehavioral symptom complex, which results from diverse triggering insults.

 

Source: Bennett B, Goldstein D, Friedlander M, Hickie I, Lloyd A. The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study. J Pain Symptom Manage. 2007 Aug;34(2):126-35. Epub 2007 Jun 4. https://www.ncbi.nlm.nih.gov/pubmed/17544246