Research Roundup: Fall 2008

Investigators from around the world continue to study CFS and publish their findings in a variety of scientific and medical journals. To help keep you abreast of what’s being investigated and published, here’s a brief rundown of some studies that have recently appeared in peer-reviewed journals.

Association-Funded Study Published on LactateIn a study published in the October 2008 issue of NMR in Biomedicine, researchers at the Mount Sinai School of Medicine and the Weill Medical College of Cornell University in New York used a sensitive and quantitative brain imaging technique that revealed elevated lactate in the ventricular cerebrospinal fluid in people with CFS. The study—funded by a grant from the Solve ME/CFS Initiative —examined 14 people with CFS, 14 people with general anxiety disorder (GAD) and 15 healthy controls and found that only the CFS subjects had significantly raised concentrations of ventricular lactate.

The ventricles are structures of the brain with cells that produce cerebrospinal fluid – the fluid that “bathes” the brain and contains a number of substances important for energy production such as glucose and lactate. The brain can use both glucose and lactate as brain fuel.

In this study, investigators used proton magnetic resonance spectroscopy imaging (MRSI) and found that the mean lateral ventricular lactate concentrations were increased by 297% in CFS compared to GAD and by 348% compared to healthy volunteers. The size of the lateral ventricles was similar for the 3 groups indicating that some physiologic process rather than physical volume likely explained elevated lactate.

The reason for this elevated lactate is not clear but is consistent with evidence of decreased brain blood flow and oxidative stress in CFS. The investigators will extend their study to increase the numbers of CFS subjects and investigate possible explanations for elevated lactate.

Reference

Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC. Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed. 2008 Oct 21. [Epub ahead of print]

POTS is three times more common in CFS patients

Researchers of the Northern CFS/ME Clinical Network and the Falls and Syncope Service at Newcastle University in the United Kingdom have been studying the prevalence of postural orthostatic tachycardia syndrome (POTS) in patients with CFS/ME. In a study published in the September 2008 issue of the Oxford medical journal QJM, the researchers conducted autonomic testing on 59 CFS patients and 52 age- and sex-matched controls and found that 27% of CFS subjects had POTS compared to 9% of controls.

The autonomic nervous system is a network of peripheral nerves that control functions such as heart rate and breathing. POTS signifies a disturbance in the autonomic nervous system and is characterized by an abnormally large increase in heart rate when an individual goes from lying on his/her back (supine) to standing.

In this study subjects wore a monitor that continuously measured heart rate and blood pressure while supine and then in a standing upright position for two minutes. Subjects were defined as having POTS if heart rate increased from 30 beats while supine to >1

20 beats per minute while standing.

There research showed that the maximum heart rate on standing was significantly higher in CFS compared to controls. Increased fatigue was also significantly associated with increased heart rate. The authors conclude that POTS occurs frequently in CFS patients and should be evaluated in people with this illness. Studies to optimize management of POTS in CFS are under way.

Reference

Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Sep 19. [Epub ahead of print]

Altered immune function causes altered neuroendocrine function in CFS

In September the journal Genomics published a paper by Jim Fuite, PhD, and colleagues–including the Solve ME/CFS Initiative’s scientific director, Suzanne Vernon, PhD, (conducted while she was working at the CDC)–describing immune cell communication differences in CFS.

Using the Wichita CFS clinical data set and some mathematical techniques to identify patterns and communication networks, the authors are able to demonstrate that people with CFS have immune system gene activity that resembles chronic inflammation. This altered immune function, in turn, affects neuroendocrine function in people with CFS. By examining data from several body systems at the same time, this is the first comprehensive assessment that demonstrates severe disturbances across multiple physiologic systems. These physiologic disturbances likely underpin CFS symptoms. (see “New Papers Drawn from CFS Dataset Underscore the Power of Partnerships” in the October 2008 CFIDSLink)

Reference

Fuite J, Vernon SD, Broderick G. Neuroendocrine and immune network re-modeling in chronic fatigue syndrome: an exploratory analysis. Genomics. 2008 Sep 4. [Epub ahead of print]

Low cortisol levels in CFS may be reversible

Evidence exists that people with CFS produce lower than normal levels of the hormone cortisol (hypocortisolism). One theory about the cause of this hypocortisolism is that it occurs well into the course of CFS due to factors such as inactivity, sleep disturbance, chronic stress and deconditioning. In this study, published in the Journal of Affective Disorders, researchers set out to determine if therapy aimed at reversing those factors would result in increased cortisol output in CFS patients.

The investigators measured the coritsol output of 41 CFS patients prior to and following six months of cognitive behavioral therapy (CBT). The results suggested that CBT treatment increased cortisol output, perhaps through its effects on sleep, stress response and physical activity levels. The investigators note that this study was not a clinical trial of CBT as a remedy for CFS, but rather a look at whether the hypocortisolism associated with CFS could be a secondary result of the illness and one that can be mediated. If further study shows that low cortisol levels can be increased through better sleep, more physical activity and/or better stress management, this could be viable treatment information for patients.

Reference

Roberts A, Papadopoulos A, Wessely S, Chaldera T, Cleare A. Salivary cortisol output before and after cognitive behavioural therapy for chronic fatigue syndrome. Journal of Affective Disorders 2008 [Epub ahead of print] November 1, 2008