Summary of Twin Study Results

I will include a brief summary of the results I have received from the Seattle Twin Study on CFS.

According to their research:

146 female twin pairs (at least one twin reported 6 months or longer of fatigue) completed questionnaire on symptoms of CFS, physical health and a psychiatric interview. Identical twins had a higher concordance rate (both twins had the same condition) than the faternal twins. The results suggests that genes (heridity) may be an important factor in the cause of CFS.

According to the Revised Ways of Coping Checklist administered to both faternal and identical twins with and without CFS revealed the pattern of coping strategies was similar for both groups. However the CFS twins used more avoidance strategies and more avoidance to problem focused coping. Both twins generally displays the same behavior patterns in coping with stress but the CFS twins used more avoidance.

According to a study of 115 twin pairs where one had CFS and the other one was healthy they found a number of conditions were higher in the fatigue twin. Fatigue twins have had a 25 times greater chance of having FM and 5 times greater chance of having irritable bowel syndrome, multiple chemical sensitivities, and temporomandibular disorder than the healthy twins.

Intensive week long study of 22 sets of twins (one meeting the 1994 CDC case definition of CFS, and the other one healthy) revealed several findings. They are still analyzing all the data but did find remarkedly disrupted sleep (alpha waves intruding in delta wave sleep), poor performance on several cognitive tests (memory) and severely impaired exercise capacity in both CFS and healthy twins. They did find some "intriguing" differences in immune function and perceptual style. As a result they will continue the study focusing on these "abnormalities" and the differences in the perception of these "abnormalities" between the two groups. (In other words why does the alpha waves keep the CFS twin from feeling they get a good night's sleep while the "healthy" twins feel they sleep sound. It should be interesting.)

The results are being published. As I get the results I will share them here.

Spect Scan results Results of the spect scan part of the CFS/FM Twin study

Results of Isoproterenol Tilt Table Testing in Monozygotic Twins Discordant for Chronic Fatigue Syndrome Results of the tilt table test part of the CFS Twin Study. 4 CFS twins & 4 Healthy twins tested positive for NMH.

CFS Twin Study: Phase 1 Abstracts Abstracts includes: Cellular immunity in monozygotic twins discordant for chronic fatigue syndrome. Studies elsewhere have suggested that immune dysfunction may be common in patients with chronic fatigue syndrome (CFS). The objective of this study was to assess the nature and extent of abnormalities in lymphocyte cell surface markers and NK cell activity in patients with CFS while controlling for genetic factors. Page includes increasing number of abstracts from the first CFS Twin Study, as I get them.

A Twin Study of Chronic Fatigue Study of the genetic influences and environmental factors in the etiology of chronic fatigue syndrome.

Chronic fatigue and anxiety/depression: a twin study Conclusions In this sample, chronic fatigue and psychological distress are strongly associated without evidence for genetic covariation, implying that the association is environmental, or due to overlapping definitions. Any genetic covariation missed is likely to involve anxiety rather than depression.

Comorbid clinical conditions in chronic fatigue: a co-twin control study. "CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention."
Comorbid Clinical Conditions in Chronic Fatigue by Leslie A. Aaron, PhD, MPH, Richard Herrell, MS, Suzanne Ashton, BS, Megan Belcourt, Karen Schmaling, PhD, Jack Goldberg, PhD and Dedra Buchwald, MD To get the entire artical you can link on this site.

Use of alternative treatments by chronic fatigue syndrome discordant twins. "Conclusions: Individuals with CFS frequently used alternative medical treatments yet rarely communicated this use to their medical doctor."

The Chronic Fatigue Twin Registry: method of construction, composition, and zygosity assignment. How the twin registry was created. "Twins completed an extensive questionnaire booklet that included measures of physical and mental health, functional status, and psychosocial factors; a structured psychiatric interview was also conducted by telephone. Twins were classified using three increasingly more stringent diagnostic criteria for chronic fatigue: 1) > or = 6 months of fatigue (115 discordant and 61 concordant pairs); 2) chronic fatigue with additional symptoms and application of the medial exclusions of the CDC CFS case definition as obtained by self-report (92 discordant and 41 concordant pairs) and; 3) chronic fatigue with additional symptoms unexplained by self-reported medical conditions and psychiatric diagnoses as determined by the structured interview (69 discordant pairs and 25 concordant pairs)."

Phase 2 related studies

Brain Scans Show Pain Sensitivity in Fibromyalgia Part of the second phase of the twin study will study the comparison of perception & brain response to pain.

Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study "Fibromyalgia syndrome displays sympathetically maintained pain features such as frequent post-traumatic onset and stimuli-independent pain accompanied by allodynia and paresthesias. Heart rate variability studies showed that fibromyalgia patients have changes consistent with ongoing sympathetic hyperactivity. Norepinephrine-evoked pain test is used to assess sympathetically maintained pain syndromes. Our objective was to define if fibromyalgia patients have norepinephrine-evoked pain."

Functional Magnetic Resonance Imaging (fMRI) "Specifically, it shows which areas of the brain are active when a person thinks, speaks, moves, feels, or remembers." Site includes a lot of info on fMR & explainations. "Observing differences in blood flow between active areas and less active areas requires "seeing" very small changes (1- 4%). These small differences require that we use statistical analyses of these images to produce reliable results. The large number of images acquired during each session (500-1200 images) necessitates significant effort, manpower, hardware, software, as well as digital storage, to process and analyze these results. These tasks demand image co-registration, mathematical correction for motion and other potential artifactual errors, and require state-of-the-art knowledge to produce reliable and valid results." At Seattle they will be looking at how the twin with CFS brain reacts to various stimuli compared to the twins who are not bothered by CFS symptoms. This should be an interesting study.

About Functional MRI Farther explaination about fMRI.

Radiologic Guide to MRI Interpretation MRI Evaluation of Chiari I Malformation
Some interesting points of interest whether this is the criteria used or not, but it's interesting.
Tonsillar position - Report mm's below foramen magnum - Configuration
Diminished CSF volume inferior and lateral to cerebellum
Small cerebellar folia
Measure AP dimension of cervical spinal canal
Cord contour changes
Decreased CSF flow basilar cisterns

Brainstem conundrum: the Chiari I malformation.

J Am Acad Nurse Pract 2001 Apr;13(4):154-9
Author: Mueller D.
Affiliation: Division of Neurosurgery, University of Missouri Hospital and Clinics, USA.
NLM Citation: PMID: 11930527

PURPOSE: To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider.

DATA SOURCES: Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies.

CONCLUSIONS: The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa.

IMPLICATIONS FOR PRACTICE: Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

National Fibromyalgia Research Association (NFRA) Funding Pilot Study on Spinal Cord Compression Dr. Michael Rosner's findings are prompting other researchers to explore the possibility of Chairi I Malformation. NFRA is funding research by Dr. Robert Bennett of Oregon Health Sciences University, Dr. I. Jon Russell of the University of Texas Health Sciences at San Antonio, and Dr. Dan Clauw of Georgetown University. However researchers are also doing MRIs of all the twins in phase 2 to see if Chairi I Malformation is present in the twins with CFS/FM as well as comparing results to the healthy twins.

The Chiari I Malformation: 1998 Experience Evaluation: MRI: MRI is the diagnostic test of choice, Crowding & tonsillar herniation, 5 mm or more herniation of the tonsils, 3-5 mm herniation -CM I if other features present

Selected Brain Mapping Sites... Want to explore more about the brain.

UCLA Brain Mapping More info on brain mapping.

Quantitative sensory testing in fibromyalgia patients and in healthy subjects: identification of subgroups. Another study of perception of heat & cold.

Background pain in fibromyalgia patients affecting clinical examination of the skin.

J Clin Nurs 2002 Jan;11(1):58-64
Raak R, Wahren LK.
Department of Caring Sciences and Sociology, University of Gavle, Sweden.

The purpose of this study was to investigate the relationship between on-going pain and acute thermal pain in patients suffering from chronic pain.

This experimental study in cold and heat sensitivity was performed in order to test the following hypothesis: that fibromyalgia patients scoring high in current background pain tolerate less experimental thermal pain in the skin than patients with low scores. Ethical aspects of the study are discussed.

The level of tolerable experimental thermal stimuli was tested and compared between the 'low-score' and the 'high-score' patients. Background pain seemed to affect the intensity of experimental cold pain. Clinical routine examinations and bodily care of the skin that might interfere with background pain in the fibromyalgia patients are discussed.

Clinical practice should be carefully planned in order to assist fibromyalgia patients in understanding and coping with thermal conditions that might influence background pain.

Factors explaining variance in perceived pain in women with fibromyalgia.

BMC Musculoskelet Disord 2002 Apr 25;3(1):12
Malt E, Olafsson S, Lund A, Ursin H.
Department of Psychiatry, University of Bergen Haukeland University Hospital, N-5022 Bergen, Norway.

BACKGROUND: We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain.

METHODS: Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge.

RESULTS: Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain.

CONCLUSION: Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients.

Quantitative and qualitative perceptual analysis of cold dysesthesia and hyperalgesia in fibromyalgia.
Pain 2002 Mar;96(1-2):177-87
Berglund B, Harju EL, Kosek E, Lindblom U.
Institute of Environmental Medicine, Karolinska Institutet and Department of Psychology, Stockholm University, SE-106 91, Stockholm, Sweden

Somatosensory perception thresholds, perceived intensity, and quality of perceptions were assessed in 20 women with fibromyalgia syndrome (FMS) and in 20 healthy age-matched female controls. All patients and controls scaled perceived intensity and described perceived quality of randomized thermal (Thermotest) and tactile (von Frey filaments) stimulation. Perceived intensity was scaled by free-number magnitude estimation and interindividual comparability was accomplished by Master Scaling. Perceived quality was assessed by choosing verbal descriptors from a list. Thenar was used as a reference for each modality tested. All patients were able to reliably scale perceived intensity at thenar, as well as in pain-affected body areas. Perception thresholds for cold pain, heat pain, cold-pain tolerance and heat-pain tolerance were significantly lower in patients than controls. For cold and tactile stimulation, the master scaled perceived intensities were significantly higher in patients' pain-affected areas, whereas for warmth/heat stimulation, the intensities were significantly lower. In the qualitative perceptual analysis the most striking and significant finding was the aberration of cold-evoked perceptions in all patients: most stimuli in the range of 30-10 degrees C were reported as heat or other paresthetic or dysesthetic perceptions. The perceptual quality of warmth, and of touch, did not differ from the controls. Another aberration was observed in the nociceptive range of thermal and of tactile stimulation as significantly more frequent pain-related descriptors than in controls. This indicates a general nociceptive facilitation in addition to the lower thermal pain thresholds. The combination of cold hyperesthesia, cold dysesthesia, and multimodal hyperalgesia suggests a selective pathophysiology at a particular level of integration, possibly in the insular cortex. It is suggested that the aberrations revealed by the supraliminal sensory evaluation may be generic for FMS. Particularly, the aberrations established in all patients for perceived quality and intensity in the cold sensory channel may be an additional diagnostic criterion.

Co-Cure Web Site

Use of actigraphy for monitoring sleep and activity levels in patients with fibromyalgia and depression.

J Psychosom Res 2002 Jun;52(6):439-43
Korszun A, Young EA, Engleberg NC, Brucksch CB, Greden JF, Crofford LA.
Department of Psychological Medicine, University of Wales College of Medicine, Monmouth House, Tenovus Building, Heath Park, CF4 4XW, Cardiff, UK

OBJECTIVE: The hallmark symptom of fibromyalgia (FM) is widespread chronic pain, but most patients are also impaired due to fatigue and sleep disturbance, and there is a strong association with depression. We compared levels of activity and sleep patterns in FM patients, with and without comorbid depression, to those of normal healthy controls and depressed patients.

METHODS: Actigraphy was carried out on 16 patients with uncomplicated FM, 6 FM patients with comorbid depression, 9 patients with recurrent major depression, and 28 healthy controls over a period of 5-7 days. The means of daytime activity levels, nighttime activity levels, and percentage time spent asleep during the daytime and nighttime were calculated and compared.

RESULTS: Controls showed high levels of activity during the day and uninterrupted periods of sleep at night. Patients with FM alone showed similar levels of daytime activity, but disturbed sleep with significantly increased levels of activity at night compared to normal controls. Patients with depression alone also showed disturbed sleep compared to normal controls. However, patients with FM and comorbid depression showed the most impairment, with significantly reduced daytime activity and significantly increased daytime sleeping compared to controls, as well as more sleep interruption and movement during the night.

CONCLUSION: Actigraphy is a useful means of studying activity levels and sleep patterns and demonstrated significant differences between FM patients with and without comorbid depression.


News & other sites with frequently updated information on FM & CFS. Sites of Research similar to studies done in phase 1 & 2.

Human Herpesvirus 6 (HHV-6) and Chronic Fatigue Syndrome & Chronic Fatigue Syndrome and Herpesviruses: the Fading Evidence. "Human Herpesvirus 6 (HHV-6) is one of eight known members of the human herpesvirus family. The virus, which was discovered in 1986 at the NCI, infects cells of the immune and central nervous system." Is this a marker for CFS? The debate continues.

Medlineplus Fibromyalgia latest news & other links & info on FM.

CDC CFS definition Complete Text of Revised Case Definition: The Chronic Fatigue Syndrome: A Comprehensive Approach to its Definition and Study "The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations. We have developed a conceptual framework and a set of research guidelines to use in studies of the chronic fatigue syndrome. The guidelines cover the clinical and laboratory evaluation of persons with unexplained fatigue; the identification of underlying conditions that may explain the presence of chronic fatigue; revised criteria for defining cases of the chronic fatigue syndrome; and a strategy for subdividing the chronic fatigue syndrome and other unexplained cases of chronic fatigue into subgroups."

Premorbid "overactive" lifestyle in chronic fatigue syndrome and fibromyalgia: An etiological factor or proof of good citizenship? This may be an influencing factor to cause increased stress which could contribute to triggering FM.
"Objective: In a former study, we have shown that patients suffering from chronic fatigue syndrome (CFS) or chronic pain, when questioned about their premorbid lifestyle, reported a high level of "action-proneness" as compared to control groups. The aim of the present study was to control for the patients' possible idealisation of their previous attitude towards action. Methods: A validated Dutch self-report questionnaire measuring "action-proneness" (the HAB) was completed by 62 randomly selected tertiary care CFS and fibromyalgia (FM) patients, as well as by their significant others (SOs). Results: HAB scores of the patients and those of the SOs were very similar and significantly higher than the norm values. Whether or not the SO showed sympathy for the patient's illness did not influence the results to a great extent. SOs with a negative attitude towards the illness even characterized the patients as more "action-prone." Conclusions: These results provide further support for the hypothesis that a high level of "action-proneness" may play a predisposing, initiating and/or perpetuating role in CFS and FM."

Journal of Chronic Fatigue Syndrome: Multidisciplinary Innovations in Research, Theory & Clinical Practice Search the journal for abstracts to learn more about research being done on CFS.

This is what it's like to sleep in a sleep lab

Ladies: Keep a Watch on That Belly Shrinking the Waistline Might Save Your Life Belly fat increases heart disease risk, especially in women. "Weight gain in women, particularly in the abdominal area, triggers inflammation in the body and significantly raises your risk of heart disease, according to a new study." If it increases inflammation and FM is a type of inflammation of the muscles, then it may also influence the degree of FM symptoms. It sounds like a viable theory which I passed onto the researchers in Seattle. (hey my sister has a larger abdomin than mine (2 kids) & severe FM symptoms. However sometimes it seems mine is growing.)

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