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Health News from NHS Choices

Constantly updated health news across a range of subjects.

NHS Choices News

  • 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



  • 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



  • 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



  • Details of autism genes uncovered in global study

    “A massive international study has started to unpick the ‘fine details’ of why some people develop autism,” BBC News reports.

    A team of international researchers looked for variations in the DNA sequences of the genes in 3,871 people with autistic spectrum disorder (ASD) and 9,937 unaffected family members or unrelated controls.

    The researchers identified 107 genes containing variations associated with ASD. In more than 5% of the people with ASD, these genes had new (not inherited) mutations that led to genes either not working at all, or working less well.

    The genes encoded proteins involved in synaptic formation, the (expression) activity of other genes, and proteins involved in modifying the packaging of DNA inside cells.

    Synapses are junctions where signals are passed from one nerve cell to another, and are found in the brain and nervous system. They are thought to be essential in underpinning consciousness, thinking and behaviour.

    This study sheds more light on ASD, but does not necessarily mean that screening for the condition is closer.

    Deciding whether screening is a good option involves considering a wide range of issues in addition to determining how well people with ASD can be identified, including an assessment of the options open to someone identified as having or being at risk of ASD.

    For example, if screening was going to be offered during pregnancy, would it be ethical to terminate a viable pregnancy on the grounds that the child would develop ASD? Many people with ASD live fulfilling and rewarding lives.

     

    Where did the story come from?

    The study was carried out by an international team of researchers and was funded by the US National Institutes of Health and other sources.

    The study was published in the peer-reviewed scientific journal Nature.

    The news stories differed in terms of the number of genes reportedly associated with ASD; these figures differed depending on what they took to be statistically significant. For the record, there was strong evidence for 22 genes and weaker evidence for another 107 genes.

    Despite headlines suggesting that autism screening is closer, this is debatable. ASD is a highly complex condition and we still don’t fully understand what causes it.

    While mutations in many genes have been found to be associated with the disorder, environmental factors may also play a role.

    None of the UK media considered whether screening for ASD would actually be desirable. As there is currently no cure for ASD, screening could offer the option of terminating a pregnancy (or rejecting an embryo for an IVF procedure).

    However, a case could be made that screening, either during pregnancy or once the child was born, would allow parents to be given information about what to expect, and treatment could be started soon after birth.

     

    What kind of research was this?

    This was a case-control study that compared the sequence of genes in people with ASD (the cases) and controls, who were either family members or unrelated people. Any changes that were only found in people with ASD, or in more people with autism than without, could be contributing to the condition. They also looked at whether these variations had been inherited by the person with ASD from one of their parents, or if they were “new” variations that had happened in their very early development.

    This is the ideal study design to identify variants that are associated with ASD. It is a complex disease, with many genes potentially associated with it – each contributing a small amount to a person’s risk. Environmental factors may also play a role. Different people with ASD may have different combinations of genetic risk factors, and some people without the condition may have some of these genetic risk factors. This complexity makes it very difficult to say for certain that all of the genetic variations identified definitely contribute to the condition, and to justify screening.

     

    What did the research involve?

    The researchers sequenced all of the parts of genes that contained instructions for making proteins (called “the exome”), and that lay on any chromosomes other than the X and Y chromosome (called the “autosomes”).

    They did this in 3,871 people with ASD and 9,937 controls, and compared them to look for variations associated with ASD. The researchers noted that this is the largest sample ever studied in this way.

    The researchers used new statistical methods to look for variations associated with ASD. Because of the large number of genes being looked at, and the multiple comparisons involved, there is a risk that some of the statistically significant associations found will be false (for example a significant association is seen when none exists). One way of overcoming this problem is to adjust the thresholds for what is considered a statistically significant result – called controlling the “false discovery rate”. For example, setting a false discovery rate of 0.05 means that 5% of significant associations would be expected to be false. The researchers looked at which genes were associated with ASD using different false discovery rates.

    The researchers also looked at what the genes with variations did in the body, to understand how they might be contributing to causing ASD.

     

    What were the basic results?

    The researchers identified 22 autosomal genes that were associated with ASD when they set the cut-off so that at least 95% of associations are expected to be true (false discovery rate <0.05).

    33 autosomal genes were associated with ASD when the cut-off was set so that at least 90% of associations seen are expected to be true (false discovery rate <0.1). Of these 33 genes, 15 were considered to already have good evidence of being associated with ASD, 11 had some previous evidence of association but not as strong, and seven had never been reported as being associated with autism before.

    When the cut-off was set so that at least 70% of associations seen are expected to be true (false discovery rate <0.30), 107 autosomal genes were associated with ASD. More than 5% of the people with ASD had new (not inherited) mutations in these genes that either stop the gene from working entirely, or make it work less well.

    This study would not have identified all genes associated with ASD risk, and the researchers estimated that, based on their results, there could be 1,150 genes contributing to autism risk.

    The genes associated with ASD contained instructions for making proteins involved in various processes, including:

    • making the junctions between nerve cells (synapses)
    • changing how active other genes are
    • modifying the packaging of DNA inside cells

     

    How did the researchers interpret the results?

    The researchers conclude that people with ASD have more loss-of-function mutations than would be expected in the population as a whole, and that these mutations are concentrated in a “handful” of genes.

    They say that their findings suggest that genes involved in synapses (nerve junctions), transcription (gene activity) and DNA packaging are involved in ASD.

     

    Conclusion

    This large study compared the sequence of the genes in 3,871 people with ASD with 9,937 unaffected family members or unrelated controls.

    Overall, 107 autosomal genes were found to be associated with ASD, with about 30% of these expected to not to be associated with the condition. These genes had new (not inherited) mutations, resulting in less or no function in more than 5% of the people with ASD. The researchers also estimated that over 1,000 genes could be contributing to autism risk. This gives some idea of how complex the genetics of autism appear to be – not all people with the condition will carry the same genetic risk factors, and some people without the condition will carry some of these genetic risk factors.

    The researchers looked at what processes the genes they identified are involved in. The genes encoded proteins involved in synaptic (nerve junction) formation, the (expression) activity of other genes, and proteins involved modifying the packaging of DNA inside cells. This gives researchers more of an idea of what might be going wrong within the cells of people with ASD.

    ASD is a complex condition, and mutations in many genes have been found to be associated with the disorder – with many more yet to be found. This study sheds more light on the condition, but we still have a lot to learn. This means that using this type of genetic information to screen for this condition is unlikely to happen in the foreseeable future.

    There is also the possibility that learning more about the genetics of ASD could lead to new treatments.

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

    Links To The Headlines

    Study points to new genetic risks for autism. BBC News, October 30 2014

    Autism screening closer as 100 genes linked to disorder are identified. The Daily Telegraph, October 29 2014

    Autism breakthrough as researchers find over 100 new genes linked to the social disorder. Mail Online, October 29 2014

    Links To Science

    De Rubeis S, He X, Goldberg AP, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. Published online October 29 2014



  • Milk may be linked to bone fractures and early death

    "Drinking more than three glasses of milk a day may not protect bones against breaking – and may even lead to higher rates of death," the Mail Online reports.

    Do not be alarmed – your milkman is no Hallowe'en death-bringer. In fact, there are many reasons to treat this news – and the research behind it – with some caution.

    The research comprised an analysis of two large Swedish cohort studies, in which a group of men and a group of women were given food questionnaires and then followed up for an average of 20 years. Researchers looked at whether how much milk they drank was linked to fractures or death during follow-up.

    In women, drinking any more than 200g of milk daily (less than one glass) was linked to increased risk of dying during follow-up. This increased risk ranged from 21% for one to two glasses to an increased risk of 93% for three or more.

    More than one glass a day was also linked to an increased risk of fractures in women. There wasn't such a clear link with either early death or fractures in men.

    However, people involved in the study may not have been able to reliably estimate their volume of milk intake per day, and there may have been various unmeasured factors influencing the outcomes.

    This was also a Swedish population, who may have distinct health and lifestyle factors or environmental influences, which means the results are not applicable to other populations.

    For example, milk in Sweden is fortified with vitamin A (unlike the UK), and high levels of vitamin A intake have been linked to an increased risk of fracture.

    These findings are undoubtedly worthy of further research, but people should not feel the need to drink less milk based on this study alone.

     

    Where did the story come from?

    The study was carried out by researchers from Uppsala University and the Karolinska Institutet in Sweden.

    It was funded by the Swedish Research Council, and one of the researchers was reported to be an employee of the Swedish National Food Agency.

    The study was published in the peer-reviewed British Medical Journal. This article is open access, meaning it can be accessed and read for free online.

    The majority of the UK's media headlines are needlessly alarmist, although the actual reporting of the study tended to be more restrained. Many of the sources include quotes from independent experts, who discuss the limitations of the study and highlight the fact Swedish milk is fortified with vitamin A.

     

    What kind of research was this?

    This was an examination of the findings of two Swedish cohort studies – one in men and one in women – which aimed to investigate whether drinking more milk is linked to outcomes of fracture or mortality (death) from any cause.

    The researchers say it is well known that a diet rich in dairy, containing high amounts of essential nutrients such as calcium and vitamin D, is considered to reduce the risk of osteoporotic fractures.

    However, they say there may be undesirable effects because milk contains D-galactose, a type of sugar (although it tastes much less sweet than other types of sugar).

    Experimental evidence in animals has suggested D-galactose is associated with ageing, with observations including oxidative stress (where damage occurs at the molecular level) to tissues, and changes to gene activity and the immune system.

    The researchers say an injected dose of 100mg/kg of D-galactose has been shown to accelerate biological signs of ageing in mice, which is equivalent to 6 to 10g in humans, or the amount found in one to two glasses of milk.

    The researchers therefore wanted to test their theory that a high consumption of milk may increase oxidative stress and inflammation in humans, and so increase the risk of mortality and fracture.

    Cohort studies are a good way of looking at whether particular exposures are associated with disease outcomes. However, they cannot prove cause and effect.

    In this study, important limitations include that the food questionnaire may not give a reliable indication of milk intake or of lifetime patterns.

    Also, there may be a variety of other health and lifestyle factors (confounders) that are influencing any association between milk intake and fractures or mortality, which the study has not been able to take into account.

     

    What did the research involve?

    This study used data from two community-based Swedish cohorts:

    • The Swedish Mammography Cohort, which recruited more than 90,000 middle-aged to elderly women from two Swedish counties from 1987-90. Food frequency questionnaires were given to the women at enrolment and again in 1997. The current study included 61,433 women who completed both of these questionnaires.
    • The Cohort of Swedish Men, which recruited more than 100,000 middle-aged to elderly men from two counties in Sweden in 1997. The men were given a single food frequency questionnaire at enrolment, and this study is representative of 45,339 men who completed this questionnaire.

    In both studies, the food frequency surveys questioned up to 96 foods and drinks consumed over the past year, including how many servings of the item per day or per week.

    Dairy items included milk, fermented milk, yoghurt and cheese, with instructions that one serving of milk equalled one 200ml glass.

    The researchers say milk intake was specified according to fat content, and they summed intake into a single measure representing total milk intake on a continuous scale.

    Looking at outcomes, the researchers examined those recorded between enrolment for the two studies and the end of December 2010. All participants were linked to the Swedish Cause of Death Registry, so the researchers could identify any deaths related to all causes, cardiovascular diseases or cancers.

    Fractures were identified by linking all participants to the Swedish National Patient Registry and by looking for any hospital admissions or outpatient visits with diagnostic codes related to fracture.

    Regarding adjustment for confounders, the researchers adjusted their analyses for many factors, including age, body mass index (BMI), total energy intake, healthy dietary pattern, calcium and vitamin D supplementation, and physical activity levels.

    The researchers assessed the risk of mortality or fracture according to categories of milk intake (less than 200g per day, 200-399g per day, 400-599g per day, and 600g per day or more) and for each additional 200g of milk per day corresponding to each additional glass of milk. They also looked at the effects of other dairy items, such as cheese and fermented milk products.

     

    What were the basic results?

    The women's cohort consumed, on average, 240g milk per day, and the men 290g – around one to two glasses day. The researchers observed a general trend that increased milk intake was associated with increased energy intake overall and increased intake of most other nutrients, while alcohol intake tended to decrease.

    Deaths

    During an average 22 years of follow-up, 15,541 women died (25% of the cohort), with a third of these deaths as a result of cardiovascular disease and a fifth related to cancer.

    The men were followed for an average of 13 years, during which time 10,112 died (22% of the cohort), with just under half of these deaths as a result of cardiovascular disease and just over a quarter caused by cancer.

    In the women's cohort, compared with drinking less than one glass of milk a day (less than 200g/day), each increasing category of intake was associated with a 21% increased risk of death from any cause for one to two glasses, and 93% increased risk for three or more glasses.

    Any intake above one glass a day was associated with an increased risk of cardiovascular death, but an increased risk of cancer death was only seen with intakes above two glasses a day.

    In the men's cohort, the link with all-cause death was less strong. Intakes above two glasses of milk per day were associated with a 5-10% increased risk of death from any cause, but the links were only of borderline statistical significance, meaning these may be chance findings.

    Looking at cause of death for men, there was a just significant increased risk of cardiovascular death above two glasses a day, but no significant link with cancer deaths.

    Fractures

    In the women's cohort, 17,252 had a fracture (28%) during follow-up, while in the men's cohort, 5,379 had a fracture (12%).

    In women, each increasing category of milk intake above less than one glass a day was associated with an increased risk of fracture of 7% for one to two glasses, and 16% for two or more. Risk of hip fracture specifically also increased with each intake above less than one glass.

    In men, there was no significant link between milk intake and any fracture, or hip fracture specifically.

    Other milk products

    No increased risk was found with increased intake of other dairy products, such as cheese or fermented milk – in fact, the opposite was seen.

    Higher intakes of other dairy products were associated with a lower risk of mortality and fractures in women. Risk reductions in men were more modest or were non-existent.

     

    How did the researchers interpret the results?

    The researchers concluded that, "High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women."

    However, they give due caution that, "Given the observational study design with the inherent possibility of residual confounding and reverse causation, a cautious interpretation of the results is recommended. The findings merit independent replication before they can be used for dietary recommendations."

     

    Conclusion

    This Swedish study found women who drink more than 200g (less than one glass) of milk a day have an increased risk of death and fractures. In men, the link between milk and risk of death or fractures was less strong.

    There was no link between milk intake and fractures, and the risk increases for death above two glasses a day were small and of borderline statistical significance.

    The study has various strengths, including its large population size of both men and women, and long-term follow-up. Also, the Swedish registries used to identify causes of death and hospital attendances for fracture are likely to be accurate and reliable.

    However, there are important limitations to bear in mind when interpreting meaning from this study, as follows:

    • The study cannot prove direct cause and effect between milk and these outcomes. Although the researchers have tried to take account of various health and lifestyle factors, the study may not have been able to fully account for the influence of these factors (for example, former or current smoking categories were considered, but within these there is going to be a wide range of frequency and duration). There may also be other unmeasured factors influencing the association.
    • There may also be the possibility for reverse causation. For example, postmenopasual women who were at risk of, or had been diagnosed with, osteoporosis could have been at an increased risk of having a fracture and may have been increasing their milk intake to try to boost their calcium levels.
    • It may be hard to reliably estimate milk intake, particularly if you consider that people do not necessarily consume measured glasses of milk per day. Milk is added to drinks or cereal, or is used in cooking. Overall, this could make it difficult to give a reliable indication of milk intake. It is also hard to know whether these food frequency questionnaires represent a lifelong pattern.
    • Also, the study relates to a specific population of Swedish middle-aged to elderly men and women. This population may have particular health, lifestyle and environmental influences, meaning their results are not generalisable to all other populations. For example, Swedish milk is fortified with vitamin A, so results may not apply to the UK, where we do not have fortified milk as standard.

    The reverse pattern – decreased risk of death and fractures in women with higher intakes of other dairy products such as cheese and yoghurt – further highlights the uncertain picture painted by these results.

    The researchers clearly acknowledge the potential limitations of their research, saying that, "Given the inherent possibility of confounding and reverse causation, a cautious interpretation of the results is recommended."

    The findings are undoubtedly worthy of further research, but people should not be overly concerned or feel the need to alter their milk intake as a result of this single study.

    A balanced lifestyle is most important for health, including taking regular exercise, not drinking too much alcohol, avoiding smoking and having a healthy, balanced diet – milk contains many important nutrients and can be part of this. 

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

    Links To The Headlines

    Dangers of more than 3 glasses of milk a day: High intake may not protect against broken bones and could actually increase chance of death. Mail Online, October 28 2014

    Three glasses of milk a day can lead to early death, warn scientists. The Daily Telegraph, October 28 2014

    High milk diet 'may not cut risk of bone fractures'. BBC News, October 29 2014

    Milk might not be as good for us as we thought, study suggests. The Independent, October 28 2014

    Three glasses of milk a day linked to earlier death. Daily Express, October 29 2014

    Links To Science

    Michaëlsson K, Wolk A, Langenskiöld S, et al. Milk intake and risk of mortality and fractures in women and men: cohort studies. British Medical Journal. Published online October 28 2014