Tag: large-scale study

Is disabling fatigue in childhood influenced by genes?

Abstract:

BACKGROUND: Medically unexplained chronic fatigue in childhood may cause considerable disability and (by definition) its cause remains unclear. A study of fatigue in healthy twins has been undertaken to examine whether or not genetic factors play a part.

METHOD: A questionnaire survey of the main carers of an epidemiological population-based sample of 670 twin pairs who were asked about periods of unexplained and disabling fatigue in their twins. Out of 1340 individuals a period of disabling fatigue was reported for 92 (6.9%). Thirty-three (2.5%) reported disabling fatigue for more than 1 month. Zygosity could be confidently assigned in 98% of the sample providing 278 monozygotic (MZ) and 378 dizygotic (DZ) pairs. These data were analysed using a structural equation modelling approach.

RESULTS: The results showed that disabling fatigue in childhood is highly familial with an MZ tetrachoric correlation (rMZ) of 0.81 and a DZ tetrachoric correlation (rDZ) of 0.59, for fatigue lasting at least a week. The most acceptable model using Akaike’s information criteria, was one containing additive genetic effects (A) and shared environment (C) plus residual (or non-shared) environment (E). For fatigue lasting at least a month rMZ was 0.75 and rDZ 0.47. The most acceptable model included just A and E. However, the role of shared environment could not be conclusively rejected.

CONCLUSIONS: Unexplained disabling fatigue in childhood is substantially familial. Both genetic and shared environmental factors are worth further exploration in a search for the causes.

 

Source: Farmer A, Scourfield J, Martin N, Cardno A, McGuffin P. Is disabling fatigue in childhood influenced by genes? Psychol Med. 1999 Mar;29(2):279-82. http://www.ncbi.nlm.nih.gov/pubmed/10218919

 

Unique genetic and environmental determinants of prolonged fatigue: a twin study

Abstract:

BACKGROUND: Prolonged fatigue syndromes have been proposed as prevalent and disabling forms of distress that occur independently of conventional notions of anxiety and depression.

METHODS: To investigate the genetic and environmental antecedents of common forms of psychological and somatic distress, we measured fatigue, anxiety, depression and psychological distress in 1004 normal adult twin pairs (533 monozygotic (MZ), 471 dizygotic (DZ)) over 50 years of age.

RESULTS: Familial aggregation of psychological distress, anxiety and fatigue appeared to be due largely to additive genetic factors (MZ:DZ ratios of 2.12-2.69). The phenotypic correlations between the psychological measures (distress, anxiety and depression) were moderate (0.67-0.79) and higher than that between fatigue and psychological distress (0.38). Multivariate genetic modelling revealed a common genetic factor contributing to the development of all the observed phenotypes (though most strongly for the psychological forms), a second independent genetic factor also influenced anxiety and depression and a third independent genetic factor made a major contribution to fatigue alone. In total, 44% (95% CI 25-60%) of the genetic variance for fatigue was not shared by the other forms of distress. Similarly, the environmental factor determining psychological distress made negligible contributions to fatigue, which was underpinned largely by its own independent environmental factor.

CONCLUSION: This study supports the aetiological independence of prolonged fatigue and, therefore, argues strongly for its inclusion in classification systems in psychiatry.

 

Source: Hickie I, Kirk K, Martin N. Unique genetic and environmental determinants of prolonged fatigue: a twin study. Psychol Med. 1999 Mar;29(2):259-68. http://www.ncbi.nlm.nih.gov/pubmed/10218917

 

Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever

Abstract:

BACKGROUND: The role of viruses in the aetiology of both chronic fatigue syndrome (CFS) and depressive illness is uncertain.

METHOD: A prospective cohort study of 250 primary care patients, presenting with glandular fever or an ordinary upper respiratory tract infection (URTI).

RESULTS: The incidence of an acute fatigue syndrome was 47% at onset, after glandular fever, compared with 20% with an ordinary URTI (relative risk 2.3, 95% CI 1.3-4.1). The acute fatigue syndrome lasted a median (interquartile range) of eight weeks (4-16) after glandular fever, but only three weeks (2-4) after an URTI. The prevalence of CFS was 9-22% six months after glandular fever, compared with 0-6% following an ordinary URTI, with relative risks of 2.7-5.1. The most conservative measure of the incidence of CFS was 9% after glandular fever, compared with no cases after an URTI. A conservative estimate is that glandular fever accounts for 3113 (95% CI 1698-4528) new cases of CFS per annum in England and Wales. New episodes of major depressive disorder were triggered by infection, especially the Epstein-Barr virus, but lasted a median of only three weeks. No psychiatric disorder was significantly more prevalent six months after onset than before.

CONCLUSIONS: Glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection if they last more than a month.

 

Source: White PD, Thomas JM, Amess J, Crawford DH, Grover SA, Kangro HO, Clare AW. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. Br J Psychiatry. 1998 Dec;173:475-81. http://www.ncbi.nlm.nih.gov/pubmed/9926075

 

Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue Syndrome

Abstract:

Mycoplasma fermentans and other Mycoplasma species are colonizers of human mucosal surfaces and may be associated with human immunodeficiency virus infection. While many infectious agents have been described in different percentages of patients with Chronic Fatigue Syndrome (CFS), little is known about the prevalence of mycoplasmas and especially M. fermentans in CFS patients.

A polymerase chain reaction (PCR)-based assay was used to detect Mycoplasma genus and M. fermentans genomes in peripheral blood mononuclear cells (PBMC) of CFS patients. Blood was collected from 100 patients with CFS and 50 control subjects. The amplified products of 717 bp of Mycoplasma genus, and 206 bp of M. fermentans were detected in DNA purified from blood samples in 52% and 34% of CFS samples, respectively. In contrast, these genomes were found in only 14% and 8% of healthy control subjects respectively (P < 0.0001).

All samples were confirmed by Southern blot with a specific probe based on internal sequences of the expected amplification product. Several samples, which were positive for Mycoplasma genus, were negative for M. fermentans indicating that other Mycoplasma species are involved. A quantitative PCR was developed to determine the number of M. fermentans genome copies present in 1 microg of DNA for controls and CFS patients.

Mycoplasma copy numbers ranging from 130 to 880 and from 264 to 2400 were detected in controls and CFS positive subjects, respectively. An enzyme immunoassay was applied for the detection of antibodies against p29 surface lipoprotein of M. fermentans to determine the relationship between M. fermentans genome copy numbers and antibody levels. Individuals with high genome copy numbers exhibited higher IgG and IgM antibodies against M. fermentans specific peptides. Isolation of this organism by culture from clinical specimens is needed in order to demonstrate specificity of signal detected by PCR in this study.

 

Source: Vojdani A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CW. Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue Syndrome. FEMS Immunol Med Microbiol. 1998 Dec;22(4):355-65. http://femsim.oxfordjournals.org/content/22/4/355.long (Full article)

 

Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases

Abstract:

Recently, we found a serum acylcarnitine (ACR) deficiency in Japanese patients with chronic fatigue syndrome (CFS). To clarify whether this ACR abnormality is a characteristic of CFS or not, we also studied the levels of serum carnitine in Swedish subjects.

Both serum ACR and free carnitine (FCR) levels in normal healthy subjects were quite different between Japanese (n=131) and Swedish people (n=46) (p<0.001). However, it is confirmed that Swedish patients with CFS (n=57) also had serum ACR deficiency (p<0.001). When we studied the levels of serum ACR and FCR in Japanese patients with various kinds of diseases (CFS, hematological malignancies, chronic pancreatitis, hypertension, diabetes mellitus, chronic hepatitis type C, psychiatric diseases), a significant decrease in the levels of serum ACR was only found in patients with CFS and chronic hepatitis type C (p<0.001).

Therefore, we concluded that ACR deficiency in serum might be a characteristic abnormality in only certain types of diseases.

 

Source: Kuratsune H, Yamaguti K, Lindh G, Evengard B, Takahashi M, Machii T, Matsumura K, Takaishi J, Kawata S, Långström B, Kanakura Y, Kitani T, Watanabe Y. Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. Int J Mol Med. 1998 Jul;2(1):51-6. http://www.ncbi.nlm.nih.gov/pubmed/9854142

 

Exploring the validity of the Chalder Fatigue scale in chronic fatigue syndrome

Abstract:

The Chalder fatigue scale is widely used to measure physical and mental fatigue in chronic fatigue syndrome patients, but the constructs of the scale have not been examined in this patient sample. We examined the constructs of the 14-item fatigue scale in a sample of 136 chronic fatigue syndrome patients through principal components analysis, followed by correlations with measures of subjective and objective cognitive performance, physiological measures of strength and functional work capacity, depression, anxiety, and subjective sleep difficulties.

There were four factors of fatigue explaining 67% of the total variance. Factor 1 was correlated with subjective everyday cognitive difficulties, concentration difficulties, and a deficit in paired associate learning. Factor 2 was correlated with difficulties in maintaining sleep. Factor 3 was inversely correlated with grip strength, peak VO2, peak heart rate, and peak functional work capacity. Factor 4 was correlated with interview and self-rated measures of depression.

The results support the validity of mental and physical fatigue subscales and the dropping of the “loss of interest” item in the 11-item version of the fatigue scale.

 

Source: Morriss RK, Wearden AJ, Mullis R. Exploring the validity of the Chalder Fatigue scale in chronic fatigue syndrome. J Psychosom Res. 1998 Nov;45(5):411-7. http://www.ncbi.nlm.nih.gov/pubmed/9835234

 

Chronic fatigue syndrome: physical and cardiovascular deconditioning

Abstract:

We investigated whether chronic fatigue syndrome (CFS) patients have physical and/or cardiovascular de-conditioning, in 273 CFS patients and 72 healthy controls.

We used laboratory tests to assess haematological, biochemical, endocrinological and immunological systems. The cardiovascular system was assessed by echocardiography and carotid echography. Body composition was determined by dual energy X-ray absorptiometry (DEXA).

CFS patients had smaller left ventricular end systolic (p < 0.001) and diastolic (p = 0.008) dimensions but thinner posterior walls (p = 0.02) than corresponding values in healthy controls. Left ventricular mass was also reduced in CFS patients (p = 0.006). Both maximum (p < 0.001) and minimum (p < 0.008) diameter of the carotid artery were smaller in CFS patients. The laboratory screening tests showed significant differences in serum albumin (p = 0.05), phosphate (p = 0.02), HDL-cholesterol (p = 0.03), HDL:total cholesterol ratio (p = 0.01), triglycerides (p = 0.02), neutrophils (p = 0.01) and thyroid-stimulating hormone (p = 0.04) between CFS patients and controls. Male CFS patients had an increased percentage of fat mass compared with healthy male subjects (p = 0.02).

This large group of CFS patients had evidence of physical and cardiovascular de-conditioning, suggesting that in these patients a graded exercise programme could lead to physical reconditioning and could increase their ability to perform physical activities.

 

Source: De Lorenzo F, Xiao H, Mukherjee M, Harcup J, Suleiman S, Kadziola Z, Kakkar VV. Chronic fatigue syndrome: physical and cardiovascular deconditioning. QJM. 1998 Jul;91(7):475-81. http://qjmed.oxfordjournals.org/content/91/7/475.long (Full article)

 

Reproductive correlates of chronic fatigue syndrome

Abstract:

A case-control study was conducted to determine whether menstrual and gynecologic abnormalities precede the onset of chronic fatigue syndrome(CFS) in women with this disorder to a greater extent than that observed among healthy controls.

We identified 150 women who met the 1988 Centers for Disease Control criteria for CFS from the Brigham and Women’s Hospital Cooperative CFS Research Center. A comparison group of 149 women being seen for nongynecologic conditions were selected from the waiting area of the Brigham and Women’s Hospital Internal Medicine outpatient department.

Women with and without CFS completed self-administered questionnaires on menstrual, reproductive, and medical history. Women with CFS reported increased gynecologic complications and a lower incidence of premenstrual symptomatology.

After adjustment for age, a somewhat greater number of cases compared with controls self-reported irregular cycles, periods of amenorrhea, and sporadic bleeding between menstrual periods. Factors suggestive of abnormal ovarian function–such as a history of polycystic ovarian syndrome, hirsutism, and ovarian cysts–were reported more often in CFS cases compared with controls. Frequent anovulatory cycles due to ovarian hyperandrogenism (PCOS) or hyperprolactinemia may increase risk for CFS through loss of the potential immunomodulatory effects of progesterone in the presence of continued estrogen production.

We hypothesize that frequent anovulatory cycles due to PCOS and/or hyperprolactinemia may explain the increased reporting of gynecologic complications and the lower reported premenstrual symptomatology observed in women with CFS.

 

Source: Harlow BL, Signorello LB, Hall JE, Dailey C, Komaroff AL. Reproductive correlates of chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):94S-99S. http://www.ncbi.nlm.nih.gov/pubmed/9790489

 

Factor analysis of unexplained severe fatigue and interrelated symptoms: overlap with criteria for chronic fatigue syndrome

Abstract:

The objective of this study was to identify factors explaining the correlations among unexplained severe fatigue of different durations (1-5 months or > or =6 months) and symptoms reported as being significant health problems during a preceding 4-week period.

Between June and December of 1994, a cross-sectional, random digit dialing telephone survey was conducted among residents of San Francisco, California. All subjects who reported having severe fatigue lasting for > or =1 month and a random sample of nonfatigued subjects were asked to participate in a detailed telephone interview. Data from 1,510 individuals aged 18-60 years who did not have medical or psychiatric conditions that could explain their severe fatigue were analyzed.

Common factor analyses identified three correlated factors (defined as “fatigue-mood-cognition” symptoms, “flu-type” symptoms, and “visual impairment”) that explained the correlations among fatigue lasting for > or =6 months and 14 interrelated symptoms. No factor explained the correlations among fatigue lasting for 1-5 months and other symptoms.

The combination of fatigue of > or =6 months’ duration and selected symptoms overlaps with published criteria used to define cases of chronic fatigue syndrome (CFS). Although symptoms described in this study were reported as appearing within the preceding month, and CFS symptoms must have been present for the previous 6 months, these results provide empirical support for the interrelations among unexplained fatigue of > or =6 months’ duration and symptoms included in the CFS case definition.

 

Source: Nisenbaum R, Reyes M, Mawle AC, Reeves WC. Factor analysis of unexplained severe fatigue and interrelated symptoms: overlap with criteria for chronic fatigue syndrome. Am J Epidemiol. 1998 Jul 1;148(1):72-7. http://aje.oxfordjournals.org/content/148/1/72.long (Full article)

 

Predictors of a medical-offset effect among patients receiving antidepressant therapy

Abstract:

OBJECTIVE: Characteristics of patients receiving antidepressant therapy were examined to identify factors that may be associated with a medical-offset effect.

METHOD: In a retrospective study, the authors analyzed claims data from a large health insurer in New England. The study subjects included 1,661 persons initiating treatment for depression with selective serotonin reuptake inhibitors or tricyclic antidepressants between July 1991 and June 1993.

RESULTS: Patients with anxiety disorders, coronary heart disease, cancer, and chronic fatigue syndrome and those remaining on their initial regimens of antidepressant therapy for at least 6 months were more likely to experience significant reductions in the costs of medical care services. The number of visits to mental health providers had no effect on the costs of medical services.

CONCLUSIONS: Specific comorbid conditions and sustained use of antidepressant drugs may be associated with a medical-offset effect for patients receiving treatment for depression.

 

Source: Thompson D, Hylan TR, McMullen W, Romeis ME, Buesching D, Oster G. Predictors of a medical-offset effect among patients receiving antidepressant therapy. Am J Psychiatry. 1998 Jun;155(6):824-7. http://www.ncbi.nlm.nih.gov/pubmed/9619157