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NHS Choices: Behind the headlines   + / -  
last updated: Sat, 01 Nov 2014 09:35:53 GMT

 Fri, 31 Oct 2014 11:00:00 GMT Brain differences linked to chronic fatigue syndrome

"Scientists find three differences in the brain [of people with chronic fatigue syndrome]," the Mail Online reports.

Chronic fatigue syndrome (CFS) affects around a quarter of a million people in the UK and causes persistent symptoms, such as fatigue, that can have a significant adverse impact on people's quality of life. The cause of CFS is unknown and the condition continues to be researched. 

The study behind this headline used a specialised type of MRI scan to examine whether there were any differences in the brain volume and structure of 15 people with CFS, compared with 14 people without.

The researchers found the volume of white matter (brain cell nerve fibres) was lower in the group with CFS. There were also some differences on the right side of the brain in the nerve fibres that connect the temporal to the frontal brain regions.

These are interesting developments in furthering our understanding of CFS. However, the study only involved a very small sample of 15 people, and we don't know how representative they are of all people with the condition.

The design of the study is able to demonstrate brain features that may be associated with the condition, but it cannot show cause and effect. We also don't know the order in which events happened.

It's not known whether these differences could have led to the development of CFS (and if so, whether they were always present, or whether some other unknown factors caused them to occur), or whether these are new changes that have occurred since the people developed CFS.

The next step would be to try to understand how these differences are associated with the condition's development.

 

Where did the story come from?

The study was carried out by researchers from Stanford University School of Medicine in California.

Financial support was provided by the Division of Infectious Disease Chronic Fatigue Syndrome Fund, and one of the authors received support from GE Healthcare.

The study was published in the peer-reviewed medical journal, Radiology.

The Mail Online's headline, "Is this proof chronic fatigue DOES exist?", casts doubt upon whether CFS actually exists. It's known CFS affects many thousands of people, with often severely debilitating consequences, so its existence is not in doubt.

However, the causes of CFS remain poorly understood. This study has tried to further understanding of the condition by examining brain features that may be associated with it. This study provides a starting point, but not the whole picture.

 

What kind of research was this?

This was a cross-sectional study that took brain scans of 15 people with CFS and a comparison group of age and sex-matched people without CFS. It aimed to research differences in the brain structure.

As the researchers explain, CFS is a debilitating condition characterised by six or more months of persistent or relapsing fatigue without any associated medical or mental health disorder.

The researchers consider that brain imaging may help inform diagnosis and prognosis, though conventional scan findings to date have been inconsistent and of limited help in any further understanding of the condition.

This study used a special MRI technique called diffusion tensor imaging (DTI). DTI measures the diffusion (movement or spread) of water through the brain tissues, which provides 3D images of the size, shape and microscopic structure of tissues.

 

What did the research involve?

The researchers scanned the brains of 15 people with CFS and compared them with 14 age- and gender-matched people without CFS. They were looking for any brain volume and structure differences between the two groups that may be linked to the condition.

People with CFS had to meet two inclusion criteria:

  • a clinical diagnosis of CFS made up of fatigue for six months or longer, with at least four other symptoms from: impaired memory or concentration, sore throat, tender lymph nodes, headaches, muscle pain, joint pain, unrefreshing sleep and malaise after exertion
  • ongoing memory or concentration problems causing severe enough impairment that a doctor thought brain imaging was necessary to confirm no other disease process was occurring

The group with CFS had an average age of 46 years. Eight people in the group were female (55%) and the average duration of their CFS symptoms was 12 years.

The age- and sex-matched comparison group were people without CFS, depression or substance use in the past year. Of 28 recruited, 14 chose to participate.

All participants completed a 20-item Multidimensional Fatigue Inventory (MFI-20), which assesses general, physical and mental fatigue, reduced motivation and activity. It is said to be a well-validated tool for assessing CFS, with higher MFI-20 scores indicating increased severity.

They also assessed whether each person was right- or left-handed or ambidextrous, as this is linked to differences in structure and volume in some brain areas.

The main analysis compared differences in brain volume and structure between the two groups using MRI (DTI) brain scans. This took into account variations in age, handedness and total brain volume.

 

What were the basic results?

The researchers found, on average, people with CFS had a lower total volume of white matter (nerve cell fibres) in their brain than people without.

They took a measure known as fractional anisotropy (FA), which gives a value between zero and one indicating the degree of diffusion of water, and whether there are any restrictions in any direction. A value of zero would mean that diffusion is the same in all directions.

They found significant differences in the FA of people with and without CFS in one particular region of the brain on the right side, called the right arcuate fasciculus. This is a nerve fibre tract that links the temporal region on the right side of the brain with the frontal region.

Most right-handed people with CFS had a maximum FA in the right arcuate fasciculus above 0.6, while those without CFS had a FA value below 0.6. They noticed that in people with CFS, FA of the right arcuate fasciculus tended to increase with disease severity.

The researchers also observed that people with CFS had areas of thickening in parts of the grey matter connected by the right arcuate fasciculus.

 

How did the researchers interpret the results?

The researchers concluded there is a loss of white matter in people with CFS. They also suggest the fractional anisotropy of the right arcuate fasciculus might be a biological indicator for CFS.

 

Conclusion

This study used a specialised type of MRI to examine whether there were any differences in the brain volume and structure of 15 people with CFS, compared with 14 people without.

They found the volume of white matter (nerve fibres) appeared to be lower, on average, in the people with CFS. There were also differences in the magnitude of water diffusion (a measure known as fractional anisotropy) in one particular white matter tract on the right side of the brain, which connects the temporal with the frontal brain regions.

These are interesting developments in furthering our understanding of CFS. But there are points to bear in mind when considering the meaning of these findings.

It must be remembered this research only used a very small sample of 15 people with CFS from the US, who may not be representative of the many thousands of people affected by this condition in the UK or elsewhere.

For example, these were people who had severe and persisting memory or concentration problems, such that their doctor thought brain imaging was required to make sure no other disease process was going on. The differences seen between these 15 people with CFS and 14 without may not be identical to differences that may be seen in a different sample.

Also, as this is a cross-sectional study, it cannot prove cause and effect: it can't tell us the order in which events happened. For example, it can't tell us whether these are structural features that occurred before people developed CFS, which may have been involved in the development of the condition, or whether these are changes that happened after the people developed CFS.

Further imagining studies in larger samples of people with this condition may reveal whether these results are consistent observations in the brain structure of people with CFS. The next step would then be to try to understand how these differences are associated with the condition's development.

These findings have no immediate treatment or preventative implications for CFS.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Is this proof chronic fatigue DOES exist? Scientists find three differences in the brain that suggest condition may not just be 'in the mind'. Mail Online, October 30 2014

Chronic fatigue syndrome is real, researchers say. CNN, October 30 2014

Links To Science

Zeineh MM, Kang J, Atlas SW, et al. Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome. Radiology. Published online October 30 2014

 Fri, 31 Oct 2014 11:00:00 GMT Genes may play a role in Ebola survival chances

"Genetic factors could play an important role in whether people survive the Ebola virus," BBC News reports. Researchers found around one in five mice remained unaffected by the infection.

Researchers investigated how mice with a different genetic make-up responded to Ebola infection. The research involved eight research strains of mice said to represent the majority of genetic variation seen across major mouse species. They were infected with Ebola and had their disease response examined.

The researchers found mice with different genetic profiles show variable disease response, ranging from complete resistance to infection with full recovery, to the disease being fatal.

Mice with resistance and those who died from the disease tended to have differences in the activity of certain genes, which was associated with differences in their immune and inflammatory response.

But the findings do not necessarily mean a similar pattern will be seen in humans, who have quite different genetics to mice.

Environmental factors such as access to good healthcare and hygiene standards (which, sadly, are of a low standard in West Africa), as well as the age, health and fitness of the person, are also likely to play a significant role in how infection with Ebola affects any individual.

Nevertheless, learning more about the genetic and immune responses to the Ebola virus could help contribute to the future creation of an effective anti-viral treatment.

Experts believe Ebola is highly unlikely to spread within the UK. To understand why, read Why Ebola risk is low for people in the UK.

 

Where did the story come from?

The study was carried out by researchers from the University of Washington and other research institutions in the US.

It was funded by grants from the US National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. 

The study was published in the peer-reviewed scientific journal Science Express on an open access basis, so it is free to read online.

The UK media's stories generally provide an accurate summary of the research, with most stating early on that the study was in mice.

However, the Mail Online's headline, "Will Ebola kill you? It depends on your genes," is overly conclusive and does not take account of the uncertainty of the research or its unproven applicability to people.

 

What kind of research was this?

This was an animal study investigating how mice with a different genetic make-up responded to Ebola infection in different ways.

The researchers explain how most animal studies examining the disease development of Ebola, or looking at the effectiveness of vaccines or treatments, have had to use primates or small mammals.

This is because when mice have been infected with Ebola in the laboratory, they don't demonstrate the same haemorrhagic syndrome (for example, complete dysfunction of the clotting system in the body) that occurs in humans.

This study specifically examined the role of host genetics in determining the severity of disease caused by Ebola infection.

 

What did the research involve?

This study involved infecting genetically diverse mice with different strains of Ebola to see if their genetics influenced the symptoms they developed, and whether they ultimately lived or died.

The study used mice from what is called the Collaborative Cross (CC) resource, a genetically diverse group of inbred mice obtained from the cross of eight mouse strains – five said to be classic laboratory strains, and three wild-type (found in nature) strains.

The eight "founder" mice strains are said to represent 90% of the common genetic variation seen across three major mouse species.

The researchers infected the eight CC founder strains with two strains of Ebola virus – a mouse strain and the wild-type strain, which doesn't normally cause haemorrhagic syndrome in mice.

They carried out a detailed analysis of the disease symptoms and the disease response in the mice.

 

What were the basic results?

When infected with the mouse strain of Ebola virus, the researchers observed different disease responses across the mice, ranging from complete resistance to infection to fatal disease. Some of the fatal cases developed disease changes consistent with haemorrhagic syndrome, while others did not.

The researchers performed more detailed analysis on two of the mouse lines – those resistant to disease and those that developed Ebola haemorrhagic fever.

Mice from both of these lines lost about 15% of their body weight in the five days following infection. The susceptible mice died on day five or six, while resistant mice fully recovered two weeks after infection.

Those that died demonstrated disease features consistent with Ebola haemorrhagic fever, including internal bleeding, prolonged blood coagulation times, spleen enlargement and liver discolouration. The resistant mice had no disease changes or alteration in their liver.

On further study, the researchers found differences in the inflammatory and immune response of mice susceptible or resistant to infection. This difference in response seemed to be mediated by differences in gene expression.

In particular, expression of the Tek gene in the liver was lower in the susceptible mice, and this was associated with onset of haemorrhagic disease. 

When infected with the wild-type Ebola strain, however, neither the susceptible nor resistant mice developed clinical disease. The animals had very low levels of the virus in their liver and spleen – up to 1,000 times lower than their levels when infected with the mouse strain.

At five days after infection, there was no longer any virus detectable, indicating that the wild-type Ebola virus is not able to replicate in mice.

 

How did the researchers interpret the results?

The researchers concluded that their results indicate genetic background determines susceptibility to Ebola hemorrhagic fever.

 

Conclusion

This research across mouse strains demonstrates that mice with different genetic profiles show variable disease response after infection with the Ebola virus. Responses ranged from complete resistance to infection with full recovery, to fatal disease, with or without changes consistent with Ebola haemorrhagic fever.

When comparing the mice that were resistant with those that developed fatal Ebola haemorrhagic syndrome, they found differences in the activity of certain genes, which was associated with different immune and inflammatory response.

However, these results in mice should not be extrapolated too far at this stage. The findings that different genetic strains of mice respond to Ebola infection in different ways does not mean the case will be exactly the same in people, who have quite different genetics to mice.

Genes may play a more or less important role in Ebola symptoms and survival in people, but at this stage we simply don't know.

Similarly, the different infection responses were seen only when mice were infected with the mouse strain of Ebola. The wild Ebola strain was not able to replicate in mice, further demonstrating the dissimilarities to human disease.

As BBC News reports, Andrew Easton, Professor of Virology at the University of Warwick, said the study "provided valuable information, but the data could not be directly applied to humans because they have a much larger variety of genetic combinations than mice".

Even if in humans (as in mice) our genetics play a role in how we respond to Ebola infection, it is unlikely to provide the whole answer. Factors such as the environment we live in – such as healthcare and hygiene standards – and our own underlying age, health and fitness are likely to play a large role in how we respond to Ebola infection.

Nevertheless, this study contributes to the wider understanding of Ebola, and may help direct further research examining the causes and effects of this devastating disease, as well as effective treatments at some point in the future.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Ebola virus: Genes 'play significant role in survival'. BBC News, October 31 2014

Ebola outbreak: Ebola may not be a deadly disease for everyone, scientists find. The Daily Telegraph, October 31 2014

Will Ebola kill you? It depends on your genes: Scientists discover DNA could determine if victims live or die. Mail Online, October 31 2014

Links To Science

Rasmussen AL, Okumura A, Ferris MT, et al. Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance. Science. Published online October 30 2014

 Thu, 30 Oct 2014 11:45:00 GMT Does paracetamol ease pain of decision making?

"Paracetamol could make difficult decisions less of a headache," the Mail Online reports. The story follows a US study that looked at whether taking paracetamol could reduce the pain of making difficult decisions.

Researchers tested their theory in two experiments where young, healthy adults were given either paracetamol or an inactive placebo.

The first experiment tested the theory that being asked to choose between two equally attractive things can cause mental discomfort.

Participants were asked to rate seven mental tasks and choose one of two they rated positively. People who took paracetamol were less negative about the rejected task than those who took a placebo, suggesting they experienced less pain in decision making.

The second experiment tested the theory of "loss aversion" – where people put greater value on personal possessions they own than those they do not. Participants were given a coffee mug – half were told it was theirs, while the other half were told it was the property of the laboratory.

All were asked to give a selling price for the mug. Those who took paracetamol set lower selling prices than those taking a placebo, presumably because they experienced lower levels of loss aversion.

This small study proves very little about the effect of paracetamol on the pain of decision making. The suggestion that we should take paracetamol every time we face a difficult decision in life is certainly not advisable. Sustained regular use is not recommended, and even a small overdose can cause potentially fatal liver damage.

 

Where did the story come from?

The study was carried out by researchers from the University of Kentucky. There is no information about external funding.

It was published in the peer-reviewed Journal of Experimental Social Psychology.

The study was covered uncritically by the Mail Online, with no comments from independent experts.

 

What kind of research was this?

This US study involved two experiments carried out in the laboratory setting, testing the theory that taking paracetamol can reduce the pain of certain types of decision making.

The researchers say people often talk of decisions being "painful". They specifically explored the theories of "cognitive dissonance" and "loss aversion".

Cognitive dissonance is the theory that if we have to choose between two equally attractive things (such as paying for a luxury holiday or buying a new car) it can cause mental discomfort.

To make this less painful, the researchers say, we rationalise the decision by adopting a negative attitude towards the choice we rejected ("I don't really need a new car" or "Sitting on the beach all day would have been boring").

Loss aversion is the theory that people endow their personal possessions with greater value than things they do not own.

The researchers say both cognitive dissonance and loss aversion involve regions of the brain associated with physical pain (the dorsal anterior cingulate cortex [dACC] and anterior insula), and hypothesise that paracetamol may reduce the pain of decision making.

 

What did the research involve?

In the first experiment, researchers recruited 112 undergraduates, three-quarters of whom were women, with an average age of 19.

They were screened for conditions that might have affected the results, including dependence conditions such as alcohol misuse or daily paracetamol consumption. They were randomised to consume 1g of paracetamol (one standard dose) or an inactive placebo pill.

After half an hour they were given descriptions of seven cognitive tasks and asked to rate their desirability. The tasks were described as puzzles, but frustratingly no detailed information was provided on the type of tasks described to the undergraduates.

The researchers then selected two tasks rated positively by each participant, who then chose which task he or she would perform later. After another half hour they were instructed to rate the tasks again and try to ignore their earlier evaluations, as they were told by the researchers that preferences can change over time.

In the second experiment, researchers recruited 95 undergraduates (just over half were women with an average age of 20) who met the same criteria as in the first experiment. They were randomised to be given either 1g of paracetamol or a placebo pill.

They were also handed a mug with the university logo. Participants were randomised again so that half were told the mug was theirs to keep, while the other half were told it was the property of the laboratory.

They were all instructed to examine the mug for 30 seconds. They were not told about the mug's true value. After 30 minutes they were instructed that they could sell the mug and were asked to list the selling price.

 

What were the basic results?

In the first experiment, participants rated their rejected task with fewer positive attributes to try to reduce any mental discomfort. However, people who took paracetamol were less negative about the rejected task compared with those taking placebo, suggesting they experienced less pain in decision making.

In the second experiment, among participants who had been told the mug was theirs, those who took paracetamol set lower selling prices than those who took the placebo drug.

People who took paracetamol and were told the mug was theirs also set lower prices than the other group, who were told the mug was not theirs.

Among all those who took a placebo, mug prices were not significantly higher among those told the mug was theirs than those told it was university property.

 

How did the researchers interpret the results?

The researchers say their experiments showed that paracetamol reduced the pain of decision making. They say that in the first experiment, paracetamol reduced participants' need to reduce discomfort by adopting a more negative attitude towards the rejected task.

In the second experiment, in which they were asked to set the price of a mug, participants who took paracetamol set lower selling prices, presumably because they experienced lower levels of loss aversion.

"Making decisions can be painful, but a physical painkiller can take the pain away," the researchers concluded.

 

Conclusion

This experimental study involved giving people paracetamol or a placebo, then asking them to take part in two very specific decision-making scenarios to test the psychological states of cognitive dissonance and loss aversion.

The results of the first experiment suggested people who took paracetamol were less negative about the rejected task than those who took a placebo, suggesting they experienced less cognitive dissonance.

The results of the second experiment found those who took paracetamol set lower selling prices than those taking a placebo, presumably because they experienced lower levels of loss aversion.

However, the researchers' hypothesis that paracetamol can help with the mental discomfort associated with decision making remains just that – a hypothesis.

There are many limitations to this study, including its small specific sample of healthy young adults, and these are highly experimental scenarios that do not necessarily relate to real-life situations.

The results also do not give a clear and consistent pattern. For example, people who took a placebo in the second experiment didn't rate the value of the mug differently regardless of whether they were told it was theirs or not, suggesting they were not experiencing loss aversion in any case.

Our capacity to make difficult decisions is a complex area that involves many factors, and the idea that any uncertainty or conflict around a decision would be removed just by taking a painkiller is surely dubious.

In any case, even if the pain of decision making was reduced, it does not seem to necessarily follow that we would subsequently then make the "right" decision.

The suggestion that we should be encouraged to slip a pill every time we face a painful decision is certainly not advisable. Paracetamol is a medical drug that is only designed to treat physical pain and reduce fever.

It is safe to use at recommended doses and for the proper reasons, but sustained regular use is not recommended – even a small overdose can cause potentially fatal liver damage.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Acetaminophen could also help to ease our anxieties: Pills could reduce the anguish of situations that cause psychological pain. Mail Online, October 29 2014

Links To Science

DeWall CN, Chester DS, White DS. Can acetaminophen reduce the pain of decision-making? Journal of Experimental Social Psychology. Published online September 22 2014


 

 
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