chronic fatigue syndrome vs fibromyalgia – Page 7

Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome

Abstract:

In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information.

This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels.

The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed.

Source: Light KC, White AT, Tadler S, Iacob E, Light AR. Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome. Pain Res Treat. 2012;2012:427869. doi: 10.1155/2012/427869. Epub 2011 Sep 29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200121/ (Full article)

Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia

Abstract:

STUDY OBJECTIVES: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that often have overlapping symptoms, including sleep-related complaints. However, differences between the 2 conditions have been reported, and we hypothesized that dynamic aspects of sleep would be different in the 2 groups of patients.

PARTICIPANTS: Subjects were 26 healthy control subjects, 14 patients with CFS but without FM (CFS alone), and 12 patients with CFS and FM (CFS+FM)-all women.

MEASUREMENTS AND RESULTS: We studied transition probabilities and rates between sleep stages (waking, rapid eye movement [REM] sleep, stage 1 [S1], stage 2 [S2], and slow-wave sleep [SWS]) and duration distributions of each sleep stage. We found that the probability of transition from REM sleep to waking was significantly greater in subjects with CFS alone than in control subjects, which may be the specific sleep problem for people with CFS alone. Probabilities of (a) transitions from waking, REM sleep, and S1 to S2 and (b) those from SWS to waking and S1 were significantly greater in subjects with CFS+FM than in control subjects; in addition, rates of these transitions were also significantly increased in subjects with CFS+FM. Result (a) might indicate increased sleep pressure in subjects with CFS+FM whereas result (b) may be the specific sleep problem of subjects with CFS+FM. We also found that shorter durations of S2 sleep are specific to patients with CFS+FM, not to CFS alone.

CONCLUSIONS: These results suggest that CFS and FM may be different illnesses associated with different problems of sleep regulation.

Source: Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia. Sleep. 2011 Nov 1;34(11):1551-60. doi: 10.5665/sleep.1396. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198210/ (Full article)

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome

Abstract:

OBJECTIVES: To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.

DESIGN: Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate). Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.

RESULTS: No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor’s transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.

CONCLUSIONS: At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A. FM-only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.

Source: Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome. J Intern Med. 2012 Jan;271(1):64-81. doi: 10.1111/j.1365-2796.2011.02405.x. Epub 2011 Jul 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175315/ (Full article)

Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that share considerable overlapping symptoms, including sleep-related complaints. However, differences between the two conditions have been reported, and we hypothesized that dynamic aspects of sleep, recently attracting scientific interests, would be different in the two groups of patients. We thus study transition probabilities between sleep stages of CFS patients with or without FM. Subjects were 26 healthy controls, 14 CFS patients without FM (CFS alone) and 12 CFS patients with FM (CFS+FM) – all women.

We studied transition probabilities between sleep stages (waking, REM sleep and Stage I, Stage II and slow-wave sleep (Stage III+IV)). We found that probabilities of transition from REM sleep to waking were significantly greater in CFS alone than in controls; we have reported previously this sleep disruption as the specific sleep problem for CFS alone [Kishi et al., 2008]. Probabilities of transitions from waking, REM sleep and Stage I to Stage II, and those from slow-wave sleep to Stage I, were significantly greater in CFS+FM than in controls; the former might indicate increased sleep pressure in CFS+FM and the latter may be the specific sleep problem of CFS+FM. These results suggest that CFS and FM are different illnesses associated with different problems of sleep regulation.

Source: Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:5391-4. doi: 10.1109/IEMBS.2010.5626478. https://www.ncbi.nlm.nih.gov/pubmed/21096267

Fibromyalgia and related conditions: electromyogram profile during isometric muscle contraction

Abstract:

OBJECTIVES: To evaluate electromyogram (EMG) profiles in patients with three related conditions: fibromyalgia, chronic fatigue syndrome, and depression.

METHODS: We studied 44 healthy volunteers, 22 patients with fibromyalgia, 11 patients with chronic fatigue syndrome, and 10 patients admitted for depression. The trapezius electromyogram was recorded during maximally sustained, bilateral, 90 degrees abduction of the shoulders. EMG signal frequency and amplitude were measured throughout the test.

RESULTS: In the fibromyalgia group, isometric contraction duration was significantly shorter than in the other two patient groups (P<0.001) and the EMG frequency and amplitude pattern indicated premature discontinuation of the muscle contraction. Findings in the chronic fatigue patients were similar to those in the healthy controls. The patients with depression had a distinctive EMG profile characterized by excessive initial motor-unit recruitment with a shift in the frequency spectrum.

CONCLUSIONS: Fibromyalgia was associated with a specific EMG pattern indicating premature discontinuation of the muscle contraction. Therefore, maximal voluntary muscle contraction tests may be of limited value for assessing function in fibromyalgia patients. Chronic fatigue syndrome patients had similar EMG findings to those in the healthy controls. The EMG alterations in the patients with depression were consistent with manifestations of psychomotor retardation.

Source: Maquet D, Croisier JL, Dupont C, Moutschen M, Ansseau M, Zeevaert B, Crielaard JM. Fibromyalgia and related conditions: electromyogram profile during isometric muscle contraction. Joint Bone Spine. 2010 May;77(3):264-7. doi: 10.1016/j.jbspin.2010.02.003. Epub 2010 Apr 22. https://www.ncbi.nlm.nih.gov/pubmed/20417143

Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndromepatients with and without comorbid fibromyalgia

Abstract:

BACKGROUND: Some think chronic fatigue syndrome (CFS) and fibromyalgia (FM) are variants of the same illness process. This would imply that CFS patients with and without comorbid FM have similar biological underpinnings. To test this, we compared serotonergic-based responses, plasma prolactin (PRL), and self-reported measures of fatigue to intravenous infusion of tryptophan among patients with CFS alone, CFS + FM, and healthy controls.

METHODS: Men and women with CFS alone or CFS + FM and healthy subjects, none with current major depressive disorder (MDD), were given 120 mg of L-tryptophan per kg lean body mass intravenously (i.v.). Before and after tryptophan infusion, blood samples were collected, and plasma PRL, tryptophan, and kynurenine concentrations were determined.

RESULTS: Women with CFS alone, but not CFS + FM, showed upregulated plasma PRL responses compared with controls. There were no differences among groups of men. Plasma tryptophan and kynurenine concentrations did not differ among groups.

CONCLUSIONS: These results indicate that women with CFS alone have upregulated serotonergic tone that is not seen in those with comorbid FM. The lack of effect in men suggests a mechanism that might explain, in part, the increased prevalence of CFS in women. The data support the interpretation that CFS in women is a different illness from FM.

Source: Weaver SA, Janal MN, Aktan N, Ottenweller JE, Natelson BH. Sex differences in plasma prolactin response to tryptophan in chronic fatigue syndrome patients with and without comorbid fibromyalgia. J Womens Health (Larchmt). 2010 May;19(5):951-8. doi: 10.1089/jwh.2009.1697. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875960/ (Full article)

Teaching medical students about medically unexplained illnesses: a preliminary study

Abstract:

BACKGROUND: This study examined how an interactive seminar focusing on two medically unexplained illnesses, chronic fatigue syndrome (CFS) and fibromyalgia, influenced medical student attitudes toward CFS, a more strongly stigmatized illness.

METHODS: Forty-five fourth year medical students attended a 90 minute interactive seminar on the management of medically unexplained illnesses that was exemplified with CFS and fibromyalgia. A modified version of the CFS attitudes test was administered immediately before and after the seminar.

RESULTS: Pre-seminar assessment revealed neutral to slightly favorable toward CFS. At the end of the seminar, significantly more favorable attitudes were found toward CFS in general (t (42) = 2.77; P < 0.01) and for specific items that focused on (1) supporting more CFS research funding (t (42) = 4.32; P < 0.001; (2) employers providing flexible hours for people with CFS (t (42) = 3.52, P < 0.01); and (3) viewing CFS as not primarily a psychological disorder (t (42) = 2.87, P < 0.01). Thus, a relatively brief exposure to factual information on specific medically unexplained illnesses was associated with more favorable attitudes toward CFS in fourth year medical students.

CONCLUSION: This type of instruction may lead to potentially more receptive professional attitudes toward providing care to these underserved patients.

Source: Friedberg F, Sohl SJ, Halperin PJ. Teaching medical students about medically unexplained illnesses: a preliminary study. Med Teach. 2008;30(6):618-21. doi: 10.1080/01421590801946970. https://www.ncbi.nlm.nih.gov/pubmed/18608944

Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia

Abstract:

INTRODUCTION: We evaluated polysomnograms of chronic fatigue syndrome (CFS) patients with and without fibromyalgia to determine whether patients in either group had elevated rates of sleep-disturbed breathing (obstructive sleep apnea or upper airway resistance syndrome) or periodic leg movement disorder. We also determined whether feelings of unrefreshing sleep were associated with differences in sleep architecture from normal.

METHODS: We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase.

RESULTS: CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night’s sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group.

CONCLUSION: CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night’s sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before. This sleep disruption may explain the overwhelming fatigue, report of unrefreshing sleep, and pain in this subgroup of patients.

Comment in: How much sleep apnea is too much? [Arthritis Res Ther. 2009]

Source: Togo F, Natelson BH, Cherniack NS, FitzGibbons J, Garcon C, Rapoport DM. Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia. Arthritis Res Ther. 2008;10(3):R56. doi: 10.1186/ar2425. Epub 2008 May 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483445/ (Full article)

Electrocardiographic QT interval and cardiovascular reactivity in fibromyalgia differ from chronic fatigue syndrome

Abstract:

BACKGROUND: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) frequently overlap clinically and have been considered variants of one common disorder. We have recently shown that CFS is associated with a short corrected electrocardiographic QT interval (QTc). In the present study, we evaluated whether FM and CFS can be distinguished by QTc.

METHODS: The study groups were comprised of women with FM (n=30) and with CFS (n=28). The patients were evaluated with a 10 min supine-30 min head-up tilt test. The electrocardiographic QT interval was corrected for heart rate (HR) according to Fridericia’s equation (QTc). In addition, cardiovascular reactivity was assessed based on blood pressure and HR changes and was expressed as the ‘hemodynamic instability score’ (HIS).

RESULTS: The average supine QTc in FM was 417 ms (SD 25) versus 372 ms (SD 22) in CFS (p<0.0001); the supine QTc cut-off <385.7 ms was 79% sensitive and 87% specific for CFS vs. FM. The average QTc at the 10th minute of tilt was 409 ms (SD 18) in FM versus 367 ms (SD 21) in CFS (p<0.0001); the tilt QTc cut-off <383.3 ms was 71% sensitive and 91% specific for CFS vs. FM. The average HIS in FM patients was -3.52 (SD 1.96) versus +3.21 (SD 2.43) in CFS (p<0.0001).

CONCLUSION: A relatively short QTc and positive HIS characterize CFS patients and distinguish them from FM patients. These data may support the contention that FM and CFS are separate disorders.

Source: Naschitz JE, Slobodin G, Sharif D, Fields M, Isseroff H, Sabo E, Rosner I. Electrocardiographic QT interval and cardiovascular reactivity in fibromyalgia differ from chronic fatigue syndrome. Eur J Intern Med. 2008 May;19(3):187-91. doi: 10.1016/j.ejim.2007.08.003. Epub 2007 Nov 19. https://www.ncbi.nlm.nih.gov/pubmed/18395162

Publication trends in chronic fatigue syndrome: comparisons with fibromyalgia and fatigue: 1995-2004

Abstract:

OBJECTIVE: In order to identify publishing patterns in chronic fatigue syndrome (CFS), we compared the annual number of peer review articles for CFS, fibromyalgia (FM), and non-CFS fatigue over a recent decade (1995-2004).

METHOD: Citations were drawn from Ovid/Medline, PsychInfo, and the Journal of Chronic Fatigue Syndrome for peer review articles focusing on CFS, FM, and fatigue for each year of the decade ending in 2004. Statistics included chi-square, tests for differences in proportions, and regression-based curve estimation.

RESULTS: The frequency of CFS peer review articles did not significantly change from the first half to the second half of the decade (1995-2004). By comparison, the output of both FM and fatigue articles significantly increased (P<.0001). A quadratic model (inverted U shape; P<.02) best fit the data for CFS annual publication frequency. By comparison, exponential models best fit the data for both FM (P<.0001) and fatigue (P<.0001) citations. The highest percentage of citations (15-16%) for both CFS and FM fell within the domains of diagnosis, physiopathology, and psychology. For fatigue, almost one third (31.4%) of the citations were focused on etiology, while psychology (11.5%) and physiopathology (10.4%) articles were the next most cited. Based on first-author affiliation, CFS articles were most likely to originate in the United States (37.7%), England (31.4%), and the Netherlands (4.9%).

CONCLUSION: The output of CFS peer review articles has not increased over the past decade, while the number of FM and fatigue articles has increased substantially.

Source: Friedberg F, Sohl S, Schmeizer B. Publication trends in chronic fatigue syndrome: comparisons with fibromyalgia and fatigue: 1995-2004. J Psychosom Res. 2007 Aug;63(2):143-6. https://www.ncbi.nlm.nih.gov/pubmed/17662750