TGI Friday! Four recently published research abstracts, 16 September 2011

Our regular Friday summary of research abstracts received this week that have not already appeared on the MEA website. This week’s research includes papers on genetic predisposition, homeopathic treatment, immunological biomarkers and XMRV.

1 Genetic predisposition to ME/CFS

BMC Neurol. 2011 May 27;11:62.

Evidence for a heritable predisposition to Chronic Fatigue Syndrome.

Albright F, Light K, Light A, Bateman L, Cannon-Albright LA.
Pharmacotherapy Outcomes Research Center, Department of Pharmacotherapy, College of Pharmacy, University of Utah, USA. frederick.albright@pharm.utah.edu

Abstract

BACKGROUND:

Chronic Fatigue Syndrome (CFS) came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV) or other murine leukemia related retroviruses (MLV) might also suggest underlying genetic implications within the host immune system.

METHODS:

We present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases.

RESULTS:

We observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p <0.001) and distant relationships (p = 0.010). We also observed significant excess CFS relative risk among first (2.70, 95% CI: 1.56-4.66), second (2.34, 95% CI: 1.31-4.19), and third degree relatives (1.93, 95% CI: 1.21-3.07). CONCLUSIONS: These analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.


2 Homeopathic treatments

J Clin Psychiatry. 2011 Jun;72(6):795-805.

Homeopathic treatments in psychiatry: a systematic review of randomized placebo-controlled studies.
Davidson JR, Crawford C, Ives JA, Jonas WB.
Department of Psychiatry and Behavioral Science, Duke University Medical Center, Durham, North Carolina, USA. jonathan.davidson@duke.edu

Abstract

OBJECTIVE:

To systematically review placebo-controlled randomized trials of homeopathy for psychiatric conditions.

DATA SOURCES:

Eligible studies were identified using the following databases from database inception to April 2010: PubMed, CINAHL, PsycINFO, Hom-Inform, Cochrane CENTRAL, National Center for Complementary and Alternative Medicine grantee publications database, and ClinicalTrials.gov. Gray literature was also searched using Google, Google Scholar, the European Committee for Homeopathy, inquiries with homeopathic experts and manufacturers, and the bibliographic lists of included published studies and reviews. Search terms were as follows: (homeopath* or homoeopath*) and (placebo or sham) and (anxiety or panic or phobia or post-traumatic stress or PTSD or obsessive-compulsive disorder or fear or depress* or dysthym* or attention deficit hyperactivity or premenstrual syndrome or premenstrual disorder or premenstrual dysphoric disorder or traumatic brain injury or fibromyalgia or chronic fatigue syndrome or myalgic encephalitis or insomnia or sleep disturbance). Searches included only English-language literature that reported randomized controlled trials in humans.

STUDY SELECTION:

Trials were included if they met 7 criteria and were assessed for possible bias using the Scottish Intercollegiate Guidelines Network (SIGN) 50 guidelines. Overall assessments were made using the Grading of Recommendations Assessment, Development and Evaluation procedure. Identified studies were grouped into anxiety or stress, sleep or circadian rhythm complaints, premenstrual problems, attention-deficit/hyperactivity disorder, mild traumatic brain injury, and functional somatic syndromes.

RESULTS:

Twenty-five eligible studies were identified from an initial pool of 1,431. Study quality according to SIGN 50 criteria varied, with 6 assessed as good, 9 as fair, and 10 as poor. Outcome was unrelated to SIGN quality. Effect size could be calculated in 16 studies, and number needed to treat, in 10 studies. Efficacy was found for the functional somatic syndromes group (fibromyalgia and chronic fatigue syndrome), but not for anxiety or stress. For other disorders, homeopathy produced mixed effects. No placebo-controlled studies of depression were identified. Meaningful safety data were lacking in the reports, but the superficial findings suggested good tolerability of homeopathy. A funnel plot in 13 studies did not support publication bias (χ(2)(1) = 1.923, P = .166).

CONCLUSIONS:

The database on studies of homeopathy and placebo in psychiatry is very limited, but results do not preclude the possibility of some benefit.


3 Immunological biomarkers

J Transl Med. 2011 May 28;9:81.

Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Brenu EW, van Driel ML, Staines DR, Ashton KJ, Ramos SB, Keane J, Klimas NG, Marshall-Gradisnik SM.

Population Health and Neuroimmunology Unit, Faculty of Health Science and Medicine, Bond University, Robina, Queensland, Australia.

Abstract

BACKGROUND:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers) in CFS/ME patients.

METHODS:

We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK) and CD8(+) T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4(+) T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2), levels of NK phenotypes (CD56(bright) and CD56(dim)) and regulatory T cells expressing FoxP3 transcription factor.

RESULTS:

Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4(+)CD25(+) T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8(+) T cells and NK phenotypes, in particular the CD56(bright) NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients.

CONCLUSIONS:

Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.


4 XMRV:

J Virol. 2011 Jul;85(14):7195-202. Epub 2011 May 4.

Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome.

Shin CH, Bateman L, Schlaberg R, Bunker AM, Leonard CJ, Hughen RW, Light AR, Light KC, Singh IR.
Source

Department of Pathology, University of Utah, 15 North Medical Drive East, Suite 2100, Salt Lake City, UT 84112, USA.

Abstract

Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently, CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blind manner using molecular, serological, and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS patients. We did not find XMRV or related MLVs either as viral sequences or infectious viruses, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the Taq polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV-related viruses, including XMRV, and the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.

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