“Women who delay pregnancy are more likely to have a child with autism,” the Daily Mail reported. It said that researchers have found that a woman of 40 has a 50% higher risk than a woman in her late 20s.

This research followed nearly 5m children from birth and compared the parental characteristics of those who developed autism with those who did not. It found that older mothers were associated with an increased risk of the child later developing autism.

This was generally well-conducted research, but it only considered a few of the many possible factors that might affect the risk of autism. The cause of autism is not known, but genetics, brain development, allergies, immunity and the environment, have all been suggested as possibilities.

Older women who want to have children should not be overly concerned by these findings. Their risk of having a child with autism remains small. Overall, only about 0.2% of the children in this study developed autism. A systematic review of these results and other similar studies may be able to determine whether the evidence supports a link between parental age and autism risk.

Where did the story come from?

The research was carried out in the US by Janie F. Shelton and colleagues from the University of California. The study was funded by grants from National Institute of Environmental Health Sciences, the U.S. Environmental Protection Agency, and the UC Davis School of Medicine and Office of Graduate Studies. The paper was published in the peer-reviewed medical journal Autism Research.

The news stories have generally reflected the findings of this paper accurately.

What kind of research was this?

Previous studies investigating if parental age affects the risk of having a child with autism have given inconclusive results. This study used a birth cohort (from birth onwards), with data available on the parents’ age and education. Using people from this cohort, a case-control study was carried out comparing the children who had developed autism with the rest of the birth cohort (the controls).

Cohort studies are the most appropriate type of study for observing whether a particular exposure affects the risk of a later outcome. This study has strengths in that it followed a large group of children (4,947,935) over 10 years, and that the exposure (mother’s age at child’s birth) definitely preceded the development of autism, (which is essential for studies aiming to establish causation). However, to further strengthen the validity of these results, steps need to be taken to ensure that other possible confounding factors have been taken into account. The difficulty with autism is that its causes are not known, so it is difficult to take into account all the possible factors that could affect risk.

What did the research involve?

The researchers obtained the records for all births in California between January 1990 and December 1999. Cases of autism were identified from this cohort using the records from routine examinations called the Early Start Report (ESR) for children under three, and the Client Development and Evaluation Report (CDER) for children over three.

A diagnosis of autism was defined as either a checkmark for ‘autism’ under Developmental Disabilities on the ESR, or an autism level of one (Full Syndrome Autism) on any CDER record, or an ICD code (a standard diagnostic code) for autistic disorder. Diagnosis data were available through to the year 2006. After excluding children from multiple births and those with missing data on parental age and education, there were 12,159 cases and 4,935,776 controls.

The researchers used this data to construct models of the relationship between parental age and autism risk, which were adjusted for (took into account) the potential confounders of the parents’ race or ethnicity, their number of previous pregnancies and births, year of birth, insurance type and sum of parental education (as a proxy measure of socioeconomic status). Parental age at birth was split into categories of: under 25, 25 to 29 (which acted as the reference group for other ages), 30 to 34, 35 to 39, and over 40.

What were the basic results?

A higher proportion of the children with autism were male. Compared to controls, autism cases were more likely to have older parents, and to be of either non-Hispanic white or Asian ethnicity. The median (average) age of mothers at the time of delivery was 30 for cases and 27 for controls, while for fathers these figures were 32 and 29, respectively.

Advancing maternal age was found to be associated with an increased risk of autism. When other possible confounders had been adjusted for, a mother of 40 or over at the time of birth was 51% more at risk of having a child with autism compared to a mother aged 25 to 29 (odds ratio [OR] 1.51, 95% CI 1.35 to 1.70), and 77% more at risk compared to a mother aged less than 25 (OR 1.77, 95% CI 1.56 to 2.00).

For a mother, the risk of having a child with autism was not influenced by the father’s age in any way.

The relationship with father’s age was not so clear. It appeared that fathers of 40 or over only had an increased risk of having a child with autism if the mother was under the age of 30 (OR 1.59, 95% CI 1.37 to 1.85). If the mother was over the age of 30, the risk from the father being 40 or over was only of borderline significance (OR 1.13, 95% CI 1.01 to 1.27).

How did the researchers interpret the results?

The researchers conclude that a woman’s risk of delivering a child who later develops autism increases throughout her reproductive years. However, a man’s risk of having a child with autism seems less influenced by his age and more by his partner’s.

Conclusion

This appears to be generally well-conducted research. It followed a large cohort of 4,947,935 children from birth to 6 to 16 years and compared the parental characteristics of 12,159 children who developed autism with the parents of children who did not develop autism. The study found older maternal age at birth increases the child’s risk of autism.

There are a few points to bear in mind with this study. The main one is that it took into account only a few of the factors that potentially affect the risk of autism (mainly proxy measures of socioeconomic status). The causes of autism are not known. Genetics, brain development, allergies, immunity and the environment have been suggested, but so far are only speculation.

Several minor limitations include the possibility that the children with autism were misdiagnosed or miscoded in the database, and that it may not be possible to directly apply the results outside of California as different social and cultural environments may affect risk.

Older women who are planning to have a child should not be overly concerned by these findings. Their risk of having a child with autism remains small – overall only about 0.2% of the children in this study developed autism. The authors report that other studies looking at the same question have had varied results. A systematic review looking at all such studies together may be able to determine why this is the case and whether the evidence as a whole supports a link between parental age and autism risk.

Links To The Headlines

Putting off motherhood increases risk of autistic child: researchers. The Daily Telegraph, February 9 2010

Autism risk rises 50% for older mothers, say scientists. Daily Mail, February 9 2010

Links To Science

Shelton JF, Tancredi DJ, Hertz-Picciotto I. Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Research 2010; Published Online: 8 Feb

Third-hand smoke is “as dangerous as cigarette fumes” according to The Daily Telegraph. The newspaper says that the third-hand smoke that lingers on things like clothes and furnishings can be as dangerous to babies and children as the exposure to second-hand smoke.

The complex research behind these reports is a laboratory study that has demonstrated that new carcinogenic substances develop when a natural substance (cellulose) is first exposed to nicotine and then to nitrous acid in the air. Although the identified compounds could potentially be inhaled, ingested or absorbed through the skin, the study did not measure how much of the substances the body absorbs or their direct effects on a person’s health. The results of these experiments will undoubtedly lead to further research into the health effects of smoke residue.

While it is plausible but unproven that smoke residue could damage health, the dangers of smoking and secondhand smoke are well established. Based on these known dangers alone it seems sensible for smokers to consider the health of others and smoke away from other people, such as outside or in a specially designated room. These types of steps are especially important in households with children and babies.

Where did the story come from?

Mohamad Sleiman and colleagues from Portland State University, University of California San Francisco, and Arizona State University in the US carried out this research. This work was supported by the University of California Tobacco-Related Diseases Research Program and published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences.

The Daily Telegraph and The Independent have covered this research. Although the newspapers correctly highlighted that the study’s findings are of concern, it is important to note that the extent of any health risks from these compounds has not been assessed by this laboratory research.

What kind of research was this?

Nicotine produced in cigarette smoke is deposited onto indoor surfaces and is reported to persist for week to months. When residual nicotine absorbed onto indoor surfaces reacts with nitrous acid (formed from nitrogen in the air) it produces chemicals called tobacco-specific nitrosamines (TSNAs). The TSNAs produced in this way are believed to be some of the most potent carcinogens present in unburned tobacco and tobacco smoke. Substantial levels of TSNAs have been found on surfaces inside smokers’ cars.

This laboratory research has assessed the formation of harmful TSNA substances on material exposed to smoke by measuring the yield of TSNAs produced when smoke was absorbed by a special cellulose material and exposed to nitrous acid for several hours.

Though the findings of this research are a concern, (which the journalists have rightly identified), the potential health risks to babies and children is only an extrapolation of this laboratory research. In other words, the health risks from ‘third-hand smoke’, or the degree of exposure that would lead to such risks (e.g. proximity to the material or length of exposure needed), has not been directly measured by this study.

What did the research involve?

This was complex laboratory research. In summary, two cellulose substances were exposed to a flow of nicotine vapour in a piece of equipment called a tubular-flow reactor. The nicotine vapour was created by circulating dry air over a beaker of liquid nicotine and humidifying the nicotine air stream. The cellulose was then exposed to the nicotine vapour for periods ranging from 10 minutes to two hours.

After the cellulose had been exposed to the nicotine, it was exposed to nitrous acid vapour created from sulphuric acid and sodium nitrite. The cellulose was also separately exposed to a mixture of nitric oxide and nitrogen dioxide gases. After these gas exposures, the cellulose was treated in a way that allowed the researchers to extract any nicotine and by-products left on the cellulose.

What were the basic results?

The major compound identified when the smoke-absorbed cellulose was exposed to nitrous acid was NNA, a type of TSNA that is not normally present in freshly emitted tobacco smoke. Although this is not known to be a carcinogen, it has been demonstrated to cause mutations in a similar way to the carcinogen N-nitrosonornicotine (NNN). Low levels of NNN were also detected in the cellulose, along with another carcinogen called NNK.

The three TSNA compounds in the cellulose were formed at a fast rate, with maximum concentration in the first hour of exposure. When the cellulose was exposed to nitrous acid for three hours, there was a greater than tenfold increase in the amount of surface-bound TSNAs.

When the smoke-absorbed cellulose was exposed to nitric oxide and nitrogen dioxide only (without nitrous acid) the researchers detected only NNA and NNK.

How did the researchers interpret the results?

The researchers conclude that the chemical process identified represents “an unappreciated health hazard” given the rapid absorption and persistence of nicotine on indoor surfaces such as clothes and skin. Their findings raise concerns about exposures to tobacco smoke residue, which some have termed ‘third-hand smoke’.

Conclusion

This is important laboratory research that has demonstrated that new carcinogenic substances develop when a natural substance (cellulose) is exposed to nicotine, and then later exposed to a nitrous air mixture.

Although the compounds identified in this study could potentially be absorbed through the skin, inhaled or ingested, this preliminary research did not aim to answer important questions over how much residue a person would absorb in a real-life situation or the direct health effects of absorbing these substances. Nevertheless, this research justifies further study into the toxicity and cancer-causing properties of the main substances identified and an investigation into the way they are absorbed by humans. The researchers would also need to directly examine the levels of these toxic compounds found on exposed skin, hair, clothes, furnishings and other materials.

While it is not yet known how much danger might be posed by third-hand smoke, the dangers of being a smoker and secondhand smoke are well established. The best advice that can be given to smokers at this time is to be considerate of the health of others and smoke away from other people, outside or in a specially designated room. These types of measures are particularly relevant in the family home, where steps should be taken to ensure that babies or children are not exposed to cigarette smoke or its by-products.

Links To The Headlines

Third-hand smoke as dangerous as cigarette fumes. The Daily Telegraph, February 9 2010

Nicotine study sparks 'third-hand smoke' fears. The Independent, February 9 2010

'Third-hand smoke' could damage health. BBC news, February 9 2010

Links To Science

Sleimana M, Gundela LA, Pankowb JF et al. Formation of carcinogens indoors by surface-mediated reactions of nicotine with nitrous acid, leading to potential thirdhand smoke hazards. PNAS: January 6, 2010

Genetic tests to determine how quickly a person will age may soon be available, according to several newspapers. The news is based on the recent discovery of a genetic variation that apparently predisposes some people to faster ageing. The newspapers suggested the research may lead to the easier identification of people at higher risk of age-related illnesses or suggested a possible key to longer lifespan.

Behind these reports is a genome-wide association study that scanned the DNA of several thousand people, identifying a gene variant associated with the length of telomeres - unique sections of DNA that shorten with age. The results suggest the variant is responsible for a small proportion of the variation in telomere length between individuals, equivalent to about 3.6 years of age-related shortening.

This well-conducted research has identified one particular gene variant, but the findings suggest there are many others that also affect the length of telomeres. Much more research will be needed before a practical application aimed at lengthening life would be possible.

Where did the story come from?

The research was carried out by Dr Veryan Codd and colleagues from King’s College, London and other academic institutions across Europe and the UK. The study was funded by the British Heart Foundation and the Wellcome Trust. Individual authors also received grants and financial support from a number of different sources. The study was published in the peer-reviewed medical journal, Nature Genetics.

This discovery was reported by several news sources, all of which highlight the potential of these results to techniques that might identify diseases early or potentially increase lifespan. The Guardian cautions that the results of this study are “unlikely to lead to drugs that dramatically extend lifespan”.

What kind of research was this?

The research was a genome-wide association study looking at whether any particular variant genetic sequences were associated with the length of a person’s telomeres. Telomeres are found at the ends of chromosomes, where they protect the rest of the DNA from damage and deterioration in order to maintain ‘genetic stability’. A genome-wide association study is the best way to assess associations between gene variants and particular characteristics in a large number of people.

The shortening of telomeres (which happens as cells divide) is considered to be a key process in biological ageing - the progressive decline over time in the body’s ability to meet its demands. Biological ageing occurs because cell damage accumulates as a result of environmental and genetic challenges. When the telomere eventually reaches a critically short length, cell death can occur.

This study was specifically looking for variants associated with the length of telomeres in leukocyte white blood cells. The length of leukocyte telomeres has been shown to be associated with the risk of several age-related diseases and has been proposed as a marker of biological ageing.

What did the research involve?

The researchers analysed the DNA of 2,917 individuals, looking for DNA variants known as single nucleotide polymorphisms (SNPs) that were associated with the length of the telomere on a particular chromosome.

The sample population comprised of 1,487 individuals with coronary heart disease taken from a British Heart Foundation study and 1,430 donors from the United Kingdom Blood Service. Their telomere length was measured using special techniques. It showed that the sample population was apparently normal and displayed telomere lengths expected for their ages. The groups of people were analysed separately and then combined.

Any SNPs that showed a strongly significant association with telomere length were investigated in a second sample population. These types of study often involve this second step, known as replication, where the results of the first are confirmed in a second separate sample of people. The researchers initially set out to replicate their first test in a further 2,020 people who participated in another study, assessing their telomere lengths using the same technique in the previous samples.

The researchers then replicated their study in another cohort of 3,256 twins, although the method of telomere measurement in this group was different to the others. A further cohort of 4,216 individuals was available for testing, meaning they had replicated the initial phase of their study in a total of 9,492 people.

Further experiments were undertaken to investigate the TERC gene, the gene closest to the DNA variant. The TERC gene is involved in maintaining the length of telomeres.

What were the basic results?

The studies identified an association between telomere length and a gene variant called rs12696304 on the chromosome 3q26. The researchers say that possessing the variant is associated with a person having a shorter average telomere length that equates to about 3.6 years of age-related telomere shortening. In other words, people with this particular variant may potentially live about 3.6 years less than those without it.

It is important to note this measure only suggests a potential effect on lifespan and many other factors will determine whether or not it actually affects lifespan.

Importantly, the researchers report that the variation in telomere length explained by this particular gene variant ranged from 0.32% to 1.0% in the different cohorts. This means that in addition to the variant identified, there are many unidentified genetic and environmental factors that affect telomere length.

There was no variation in the TERC gene associated with telomere length, but the researchers say that this does not “preclude the possibility that the association with telomere length is mediated by an effect on TERC expression”. This means that it is possible that the TERC gene may be having an effect on telomere length in a process yet to be uncovered.

How did the researchers interpret the results?

The researchers emphasise the importance of telomeres in cell function and how telomere length is related to its role. They say the findings have a “broad relevance for both normal and pathological age-associated processes”.

Conclusion

This study increases the information we have about the biology of ageing. In particular, it shows an association between a gene variation and short telomeres (which have a known association with ageing).

The study was well conducted and the results are reliable. The researchers have used recognised methods in this field of research and checked their initial findings in several different separate groups of people to confirm the validity of their early associations. Their ultimate conclusion is also based on the variants that were significant across all of the cohorts analysed.

It is important to remember that while the researchers have found clear associations for a particular gene, many other genes are likely to play a combined role in ageing. In fact, the study found that the variation in telomere length, explained by this particular gene variant, ranged from 0.32% to 1.0% in the different cohorts. This means there are many other factors affecting telomere length that have yet to be identified. These are likely to be other genetic factors, although environmental factors may also play a role.

Further studies will be needed to translate these findings into technologies that can screen people for a potential raised risk of age-related diseases or improve the lifespan of individuals. The study furthers our knowledge of biological ageing but the findings also suggest that there are many other factors yet to be discovered that affect telomere length.

Links To The Headlines

Genes reveal 'biological ageing'. BBC News, February 8 2010

Genetic variant means some people are predisposed to age quicker. The Times, February 8 2010

Living fast? Scientists show lifespan is linked to DNA. The Guardian, February 8 2010

Ageing gene found by scientists could be key to longer lifespans. The Daily Telegraph, February 8 2010

Genetic test for ageing may soon be possible. The Independent, February 8 2010

Links To Science

Codd V, Mangino M, van der Harst P et al. Common variants near TERC are associated with mean telomere length. Nature Genetics: Published online February 7 2010

Scientists have discovered a pill that heals brittle bones, reported the Daily Mail. It said the easily administered, once-a-day drug makes brittle bones strong again. The newspaper added that tests had been carried out on animals “but the researchers believe the treatment could one day help humans with fragile bones”.

As the newspaper pointed out, this research was carried out in mice and there are important differences in bone metabolism between mice and humans. This well-conducted study paves the way for future research into a compound called LP533401 as a potential treatment for osteoporosis, but it is too soon to herald this as a cure. The results must be replicated in humans before it is clear how this compound affects human health.

Where did the story come from?

The study was carried out by Dr Vijay K Yadav and colleagues from the Columbia University Medical Center and other medical and academic institutions in the US and India. The study was funded by grants from the US National Institutes of Health and a fellowship to one author from the International Bone and Mineral Society. The study was published in the peer-reviewed medical journal Nature Medicine.

This study explored whether osteoporosis could be treated by preventing the production of a gut-derived serotonin known to inhibit bone formation. While this drug may one day prove to be a successful treatment for osteoporosis in humans, the research was conducted in mice and the Daily Mail has been overly optimistic in heralding this as a cure after such early research.

What kind of research was this?

Serotonin is a neurotransmitter best known for its role as a chemical messenger in the brain, but it is also produced in large quantities in the stomach. The gut-derived serotonin regulates bone formation by inhibiting the growth of the early bone cells, called osteoblasts. This laboratory research in mice investigated whether osteoporosis could be treated by stopping this serotonin from being produced, thereby increasing bone formation.

The bone resorption (bone loss) characteristic of osteoporosis is currently treated with intermittent injections of parathyroid hormone (PTH) which increases bone formation. PTH must be injected and can only be used for a two-year period, so the search continues for other treatments that would be as effective but easier to use. Osteoporosis is also treated with bisphosphonates, a class of drugs that prevent bone digestion. This study did not compare the effects of the new drug with these types of treatments.

What did the research involve?

Researchers developed a compound known as LP533401, a chemical that inhibits the production of gut-derived serotonin. LP533401 is currently being tested at a dose of 100mg per kilogram of body weight for the treatment of irritable bowel syndrome. Previous studies have shown that the amount of LP533401 in the brain is negligible after being taken orally, suggesting it cannot cross the blood-brain barrier. The researchers note that this is important because brain-derived serotonin is important for healthy bone development (the opposite of gut-derived serotonin).

There were several steps to this study, with some experiments conducted in cells in culture and others conducted in living mice. In cells, LP533401 was demonstrated to inhibit the production of serotonin and there was a ‘dose-dependent’ reduction (ie the greater the dose, the greater the effect) in the levels of serotonin in the blood when mice were fed with LP533401.

Complex biochemical modelling was carried out to investigate how LP533401 interacts with other chemicals to prevent the production of gut-derived serotonin. The main animal experiments involved female mice that had had their ovaries removed (to simulate postmenopausal activity and the resulting bone resorption). The researchers investigated whether varying doses of LP533401 could prevent bone loss induced by removal of the mouse ovaries.

The researchers also investigated whether treatment with LP533401 could reverse osteopenia (the reduction in bone density that precedes osteoporosis) in mice. A group of mice had their ovaries removed and were then left untreated for two weeks. Some of these mice were then treated with LP533401 while others were given placebo, and the effects were compared four weeks later.

Another group of mice was left for six weeks after their ovaries were removed so that they developed more severe osteopenia. Some of these mice were then given LP533401 every day for six weeks and then compared with a group who were given the placebo. Further experiments were carried out to ensure that the drug was not having adverse effects on the gut.

The effects of LP533401 were also compared with those of PTH, the standard against which any new anabolic bone agent (ie bone building) should be compared.

What were the basic results?

Mice treated with LP533401, regardless of the dose, had higher bone mass (lower levels of resorption) than those not treated. The increase in bone mass was due to increases in osteoblast numbers, bone formation rate and in the levels of chemicals important for the development of healthy bone. In mice with osteopenia, LP533401 was able to increase bone formation to the degree that bone mass was normalised. Treatment of severe osteopenia saw bone mass return to normal levels.

The increase in bone mass was seen in vertebrae and in the long bones (although it did not affect bone length or width). There appeared to be no adverse effects on the gut in terms of gastric emptying or colon function. There were also no negative effects on platelets in the blood or clotting time.

LP533401 clearly had similar effects to PTH on bone recovery but at lower doses. However, a high dose of PTH was more efficient than LP533401 in the long bones, suggesting they may have different mechanisms.

How did the researchers interpret the results?

The researchers say that their results confirm that LP533401 can “rescue… ovariectomy-induced osteoporosis in mice even when given at a low dose (25mg per kilogram of body weight per day) and late after ovariectomy”. It does this without any adverse effects on blood or intestine function. They say these effects appear to be specifically due to an increase in the number of osteoblasts and the bone formation rate.

The researchers acknowledge that because of important differences between bone formation in mice and humans, their “results need to be confirmed in other species”. They suggest that drugs that can inhibit gut serotonin are potentially a new class of drugs for treating osteoporosis.

Conclusion

This well-conducted animal study paves the way for future research into LP533401 as a potential treatment for osteoporosis. This is early research and the researchers note that there are important differences in bone metabolism between mice and humans. As such, the study must be replicated in humans before it is clear whether this compound will affect human health. Also, it is unknown whether a low level of gut-derived serotonin might have unwanted effects in humans and this will need investigation.

Serotonin is an essential chemical messenger in both the brain and the gut, where it regulates intestinal activity. This research suggests that ingestion of a serotonin inhibitor, and subsequent inhibition of gut-derived serotonin, has no apparent adverse effects on gut health. However, there were no long-term follow-ups and most importantly this is a finding in mice only.

The study compares the new drug with PTH, the hormone that is currently used to encourage bone formation. However, the researchers did not compare it with other treatments for osteoporosis, such as bisphosphonates. These are also commonly used in humans but work differently (they prevent bone degeneration by osteoclasts but do not affect the osteoblasts that create new bone).

The Daily Mail has been overly optimistic in suggesting this may be a new cure for osteoporosis. It may one day prove to be an effective treatment, but there is a lot of research to be done before this becomes clear.

Links To The Headlines

Is this the cure for osteoporosis? Scientists discover pill that heals brittle bones. Daily Mail, February 8 2010

Links To Science

Yadav VK et al. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nature Medicine 2010; Published online February 7 2010

“An 'artificial pancreas' can be used to regulate blood sugar in children with type 1 diabetes,” BBC News reported.

This story is based on research on how to optimise devices that can sense glucose levels and adjust the amount of insulin a child with type 1 diabetes receives overnight. This is important in maintaining glucose levels while a child sleeps where standard glucose monitoring is not practical.

This was a small but well-conducted study that showed promising results for this technology in keeping glucose levels within an acceptable range overnight. However, further research would be needed before a commercially available system were to be available.

Where did the story come from?

This research was carried out in the UK by Dr Roman Hovorka and colleagues from the University of Cambridge. The study was published in the peer-reviewed medical journal The Lancet.

The research was funded by the Juvenile Diabetes Research Foundation, the European Foundation for the Study of Diabetes, the Medical Research Council and the National Institute for Health Research - Cambridge Biomedical Research Centre.

Generally, the press did not examine the science behind this story too deeply and the small size of this study should be highlighted as it means that further research may be needed to check how well the technology might work outside of a research institution. The media also said that the research was carried out over 54 days, suggesting that the child patients received this treatment for almost two months. However, the children received overnight treatment on one to four occasions only.

What kind of research was this?

This randomised crossover study investigated whether a new system for delivering insulin could prevent nocturnal hypoglycaemia (low blood sugar at night) in both children and adolescents.

Type 1 diabetes occurs because your body cannot produce any insulin, a hormone that is needed to control the amount of glucose (sugar) in your blood. When you eat, your digestive system breaks down food and passes its nutrients into your bloodstream. Normally, insulin is produced by your pancreas to take any glucose out of your blood and move it into your cells where it is broken down to produce energy. However, if you have type 1 diabetes, there is no insulin to move glucose out of your bloodstream and into your cells.

If you have type 1 diabetes, you will need to take insulin injections for life. You must also make sure that your blood glucose levels stay balanced by eating a healthy diet and carrying out regular blood tests.

Monitoring glucose levels and administering insulin is problematic while diabetic patients are asleep. One treatment is to continually infuse insulin overnight, but the infusion is given at a constant rate and it does not respond to changing glucose levels during sleep.

Continuous glucose monitoring devices and insulin pumps have been developed and combined to form systems where the insulin is delivered as required based on measured glucose levels.

As yet, these ‘closed loop systems’ have not managed to deliver optimal accuracy and reliability. These researchers wanted to assess whether the drawbacks of existing closed loop systems prototypes could be overcome by adjusting the control algorithms.

In this type of crossover study, participants are given either a new treatment or the standard treatment in their first session, followed by the alternative in a second session. This allows the researchers to compare two treatments tested at different times in the same patient.

What did the research involve?

Children aged between 5 and 18 years with type 1 diabetes were enrolled between April 2007 and September 2008. Sometimes it is difficult to assess children from how they are physically feeling on whether they are hypoglycaemic. The researchers excluded children who had, on several occasions in the past, severe hypoglycaemia but had not been aware of it. They also excluded children who had any type of nerve damage.

The study had three parts, the first of which was a crossover study comparing the closed loop delivery system with continuous insulin delivery overnight. The second part looked at the closed loop system overnight when the participants had received a slowly or rapidly absorbed meal (high or low glycaemic index). The third looked at the closed loop system versus the continuous insulin infusion when the participants had exercised prior to sleeping.

For the first part, 13 patients were treated with an overnight treatment or standard treatment on two occasions one to three weeks apart. The insulin pump delivery was optimised for each patient by analysing their glucose levels periodically over a 72-hour period two weeks before the first treatment.

The second part involved seven patients from the first part of the study, who were aged fom 12 to 18 years and were studied on two further occasions. These patients were asked to eat meals that had either a high or low glycaemic load. This relates to the amount of carbohydrate a food has and how quickly the food affects blood sugar levels. The patients were then put on the closed loop system overnight. On the second occasion, they received the alternative meal.

The third part of the study involved 10 patients aged between 12 and 18 years. These patients did an exercise test so they could determine an appropriate level of exercise for the children who were of different ages and may have had different levels of fitness.

The patients’ oxygen intake was measured both at rest and when they were exercising on a treadmill at 50% of their peak level for 15 minutes.

The exercise test was performed before the patients were assigned to either the overnight treatment with continuous insulin infusion or the closed loop system.

The glucose levels of the sleeping patients were continuously monitored during all treatments to check whether they were in the appropriate range. The researchers also compared different algorithms for working out how much insulin to give based on the glucose levels in the closed loop system.

What were the basic results?

In the first part of the study, the patients’ glucose levels were in the target range for longer in the closed loop group compared with the continuous infusion, but this was not statistically significant. There was no difference between continuous infusion and the closed loop system in preventing hypoglycaemia. On average, the closed loop system and the continuous infusion system administered the same insulin dose.

The patients’ blood glucose levels were the same using the closed loop system following high or low glycaemic load meals.

Patients who had been given the closed loop delivery system after evening exercise spent more time within the optimum glucose range, but this was not statistically significant.

No significant differences between the two systems were found from the individual parts of the study. However, when the data from all three parts was pooled, it showed that patients who had closed loop treatment spent longer within the target glucose range than those who had the continuous infusion. They also spent less time with levels of glucose that were lower than the target range. This was also the case when patients had initial high or low glucose levels.

How did the researchers interpret the results?

The researchers conclude that overnight manual closed loop insulin delivery can improve glucose control and reduce the risk of hypoglycaemia in young patients with type 1 diabetes. They say that sensing errors are perceived to be the main obstacle for safe and effective closed loop glucose control. However, in their study the glucose sensors on the closed loop system and the blood glucose sensors were the same. The researchers suggest that advances in glucose sensing can further improve the performance of closed loop systems.

Conclusion

This study found some evidence that closed loop systems are better at maintaining appropriate glucose levels overnight than continuous insulin infusion in children and adolescents.

Further larger studies would be useful in assessing and optimising the technology. If the same study were to be carried out in a larger sample of patients, important differences between the two systems might become more apparent.

This small but well-conducted study is a step forward in managing blood glucose levels overnight, with the potential for improving the quality of life for young patients with type 1 diabetes. Further research would be needed before a commercially available system were made available.

Links To The Headlines

'Artificial' pancreas offers hope for type 1 diabetes. The Daily Telegraph, February 5 2010

Artificial pancreas hope for children with diabetes. BBC News, February 5 2010

Links To Science

Hovorka R, Allen JM, Elleri D et al. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. The Lancet, [Early Online Publication], February 5 2010

“Playing football is better for your health ‘than going for a run or lifting weights,’” according to The Daily Telegraph.

The news is based on research that compared how football and running affected the health of people with slightly raised blood pressure. The study followed men for 12 weeks as they either played football or ran on a treadmill. The results show that regular sessions of either exercise were beneficial for fitness, weight loss and building muscle.

This research adds yet further weight to the large amount of evidence supporting the numerous benefits of regular exercise. However, while the study has confirmed benefits of both activities, it has the drawback of being too small to assess whether football is better for you than running.

Where did the story come from?

This research was carried out by Dr Knoepfli-Lenzin and colleagues from the University of Zurich, Switzerland. The study was funded by the FIFA Medical Assessment and Research Centre.

The study was published in the peer-reviewed medical journal the Scandinavian Journal of Medicine & Science in Sports.

What kind of research was this?

This was a controlled trial that looked at how playing football affected blood pressure, fitness levels and weight. It compared the effect of regularly playing football to running regularly and sedentary behaviour (no exercise).

The researchers say previous studies have shown that running and football can reduce blood pressure, increase lung function and reduce fat. They add that playing football can also build muscle mass and lower cholesterol. The researchers wanted to compare the effects of either playing football, running or no exercise in men with mild hypertension (high blood pressure) or with risk factors, such as high body mass index, that may contribute to the condition.

This was a very small study, with only 15 to 17 people in each group. Ideally, a study of this type should follow a larger number of participants in order to ensure that any differences in the groups’ results were not down to chance.

What did the research involve?

The study enrolled 47 male non-smokers aged between 20 and 45 years.

The researchers took measurements of diastolic blood pressure (when the heart is at rest) and systolic blood pressure (while the heart contracts or beats). Participants had a systolic blood pressure of 120-150 mmHg and a diastolic blood pressure of 80-95 mmHg, meaning it was higher than a normal value of 120 over 80 but not extremely high. They all had blood glucose concentration of < 7mmol/L indicating that none had diabetes. The participants were not taking any medication and showed no heart rhythm abnormalities.

Participants were then allocated to three different study groups: 15 to the football group, 15 to the running group and 17 to the ‘control group’ who did no exercise.

The football group was asked to train for one hour three times a week for 12 weeks on a small-sized football pitch. The running group was asked to train for one hour, three times a week for 12 weeks of constant running at 80% maximal (peak) heart rate. The participants in the control group made no changes to their sedentary lifestyles.

Before starting their training, all 47 participants performed incremental exercise tests to assess their fitness, such as running on a treadmill, exercise bike sessions and ‘yo-yo’ running, which assessed how well they could perform short bursts of running with a brief rest in between. The researchers also performed a Dual-energy X-ray absorptiometry (DXA) scan to assess fat and muscle distribution in the body. The researchers also measured the participants’ resting heart rate.

The set of measurements was repeated at the end of the training period.

What were the basic results?

The researchers found that after the intervention period systolic and diastolic blood pressures had reduced in all groups, including the control group. They found:

• In the football group systolic pressure reduced by 7.5% and diastolic pressure by 10.3%.
• In the running group systolic pressure reduced by 5.9% and diastolic pressure by 6.9%.
• In the control group systolic pressure reduced by 6.0% and diastolic pressure by 4.7%.

The researchers say that these before and after measures were all statistically significant (p<0.01).

However, most comparisons between the groups were not significant except where the difference in diastolic blood pressure in the football group was compared with the diastolic blood pressure difference in the control group (p<0.05).  The difference between football and running on blood pressure was not statistically significant.

The participants’ heart rates were measured when they were lying down and while they were standing up. Heart rates while lying down were lower at the end of the study for each group. In the standing position, the heart rate was only reduced in the football and running groups.

Both training groups showed a reduction in body mass and total fat mass during training. In the football group, the participants had a smaller waist and waist-to-hip ratio after training. Both training groups had also lost fat from their hips and thighs. The control group showed no differences in fat mass.

Cholesterol was lowered in the football and control groups after the training period. However, both groups had higher starting levels of cholesterol than the running group, and the cholesterol levels did not appear to vary greatly between the groups.

When they repeated the exercise tests, the researchers found that the footballers and runners performed better on the cycling test than people in the control group. They showed better lung function and performance in the treadmill and yo-yo running test after training.

How did the researchers interpret the results?

The researchers concluded that mildly hypertensive people receive at least the same cardiovascular and metabolic health benefits from playing football as they would through endurance exercise such as running.

Conclusion

This was a very small study that showed that both football and running improved fitness over a 12-week period, by reducing body fat and improving lung function. However, while The Daily Telegraph suggested that the footballers saw their blood pressure fall by an average of twice as much as the runners, this is misleading. The researchers did not find a statistically significant difference in the blood pressure reduction seen between the groups.

Other points to note:

• Although it was possible to compare the before and after effects for each type of exercise, and some of the differences found were statistically significant, the numbers in the study were too small to compare which type of exercise is better for you.
• The cholesterol levels in the three study groups varied prior to the activity period, meaning the changes seen in the football and control groups may have been due to differences between the recruits.
• There was a decrease in resting heart rate over the study period in all groups when they were lying down. As the researchers acknowledge, this may be due to the participants being more relaxed about the tests once they were were familiar with them.

When judged in isolation this small study shows that both running and football can have benefits for your health, but it is too small to provide evidence of which has greater health benefits. However, the study adds to the very large body of evidence on the benefits of regular exercise and shows that team activities are a healthy alternative to solo sports.

Links To The Headlines

Playing football better for your health 'than going for a run or lifting weights'. The Daily Telegraph, February 5 2010.

Links To Science

Knoepfli-Lenzin C, Sennhauser C, Toigo M et al. Effects of a 12-week intervention period with football and running for habitually active men with mild hypertension. Scandinavian Journal of Medicine & Science in Sports. [Published online] February 2 2010

Last updated: 11.00 BST

The National Pandemic Flu Service, set up to offer online and telephone assessments for people worried that they might have swine flu, is to close next week, Gillian Merron, the public health minister, said today.

The number of new swine flu cases has fallen to a point where the service is no longer needed. It will stop offering assessments from February 11.

The service, to assess patients and enable them to get antiviral medicine if needed, was set up in the first wave of the pandemic to ease pressure on GPs and the NHS.

Over the Christmas period, new cases of swine flu in England fell to their lowest level since the early stages of the outbreak.

The Department of Health said today: "Our priority remains to vaccinate those most at risk from swine flu, as people are still in hospital from the virus and sadly some have died.

"This is the first time we have had a vaccine to protect people while a pandemic virus has been circulating, so it has undoubtedly helped us save lives. People who are being vaccinated now may also be protected against swine flu next winter.

"However, given the current welcome reduction in the number of cases, and the need to make sure our response to the pandemic remains proportionate, we have decided to close the National Pandemic Flu Service, including the online and phone self-care service, at 1am on February 11 2010.

"If required we can have the NPFS back up and running in seven days."

If after the service closes you think you have swine flu symptoms, you should stay at home and contact your GP who will be able to assess you and authorise antivirals if you need them. Your GP will also be able to advise you on vaccination.

Swine flu cases

The latest available figures show that:

• In England, the rate of GP consultations for flu like illness was 12.5 per 100,000 population for the week ending January 31 2010.
• There were then 124 patients in hospital with swine flu in England, 29 of whom were in critical care.
• The Health Protection Agency's overall estimate of the number of cases was below 5,000, where it had been for six weeks.

Vaccination programme

By the end of January:

• The total estimated number of front-line health and social care workers vaccinated in England was 393,000.
• The total number of vaccine doses administered to the priority groups in England was 4.25 million. This figure includes 140,000 pregnant women and 404,000 healthy children aged six months to under 5 years.

Commenting on the decline in swine flu cases, Sir Liam Donaldson, chief medical officer for England, said:

“Levels of pandemic ‘flu are currently very low virtually concluding the second wave of the infection in this country.

“Although throughout it has not been a severe illness for most people, children and younger adults have developed serious complications, been admitted to hospital and some have died.

“I strongly advise that those eligible for the vaccine who have not yet had it, get the jab and protect themselves."

Vaccinations

Vaccination of people in clinical risk groups is still ongoing, with an estimated 4.25 million doses of vaccine administered so far. NHS hospitals and GPs are continuing to vaccinate young children and adults facing the greatest risk of complications. Patients will be contacted by their GPs if they fall into one of the at-risk categories.

Healthcare staff dealing with the public are also being vaccinated to help keep medical services running smoothly and to prevent them from passing the virus to patients.

Who is a priority for vaccination?

People who are most at risk from swine flu need to be vaccinated first. These groups are, in order of priority:

• People aged between six months and 65 years in the seasonal flu vaccine at-risk groups.
• All pregnant women. The European Medicines Agency has indicated the vaccine can be given to pregnant women regardless of their stage of pregnancy.
• People who live with those whose immune systems are compromised, such as cancer patients or people with HIV/AIDS.
• People aged 65 and over in the seasonal flu vaccine at-risk groups.
• Healthy children aged over six months and under five years old.

Frontline health and social care workers have also been offered the vaccine at the same time as the first clinical at-risk groups. Health and social care workers are both at an increased risk of catching swine flu and of spreading it to other at-risk patients.

What are the seasonal flu vaccine at-risk groups?

These are people with:

• chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD),
• chronic heart disease, such as heart failure,
• chronic kidney disease, such as kidney failure,
• chronic liver disease, such as chronic hepatitis,
• chronic neurological disease, such as Parkinson's disease,
• diabetes requiring insulin or oral hypoglycaemic drugs, and
• immunosuppression (a suppressed immune system), due to disease or treatment.

Who is at greatest risk of serious complications from swine flu?

Some people are more at risk of complications if they catch swine flu, and need to start taking antivirals as soon as it is confirmed that they have the illness. Doctors may advise some high-risk patients to take antivirals before they have symptoms, if someone close to them has swine flu.

It is already known that people are particularly vulnerable if they have:

• chronic (long-term) lung disease,
• chronic heart disease,
• chronic kidney disease,
• chronic liver disease,
• chronic neurological disease (neurological disorders include motor neurone disease, multiple sclerosis and Parkinson's disease),
• immunosuppression (whether caused by disease or treatment), or diabetes mellitus.

Also at risk are:

• patients who have had drug treatment for asthma in the past three years,
• pregnant women,
• people aged 65 and over, and
• children under five.

"A man who was presumed to be in a vegetative state for five years has answered questions using his thoughts alone", reported The Times. It said the research could allow some patients who are “locked in” by brain injuries to communicate.

The news is based on a three-year study in 54 patients in a vegetative or minimally conscious state. The patients’ brains were scanned with a technique called functional magnetic resonance imaging (fMRI) to detect signs of awareness. In one man, previously thought to be in a persistent vegetative state, the researchers were able to elicit the correct responses to five out of six questions.

These results confirm that some patients who meet the current criteria for being in a vegetative state are diagnosed incorrectly and retain thinking and awareness. It should be highlighted that this occurred in only one of the patients tested, and it is unknown how many people are likely to be in the same state.

The researchers say there is a high rate of error (approximately 40%) in diagnosing this group of patients. It appears the use of fMRI scanning may add another layer of safety in the diagnosis of consciousness following brain injury. However, the potential that the technique will lead to better care for patients in vegetative states, for example by allowing them to communicate their wishes, will need further research.

Where did the story come from?

This study was carried out by Dr Martin Monti and colleagues from the Medical Research Council Cognition and Brain Sciences Unit, the Impaired Consciousness Study Group and the Division of Academic Neurosurgery, all in Cambridge, along with international colleagues from the University of Liege and University Hospital of Liege in Belgium. The study was supported by several organisations and received grants from the Medical Research Council and the European Commission. The study was published in the peer-reviewed New England Journal of Medicine.

Some newspapers have incorrectly used the terms ‘coma’, ‘vegetative state’ and ‘locked in’ outside their technical definitions. For example, it is wrong to say that the study shows that “patients in 'vegetative' state can think and communicate” or “that one-in-five patients in a persistent vegetative state may be able to communicate,” as The Daily Telegraph does. The number of people who may be able to communicate usefully may be quite small. The newspapers reported that there are normally fewer than 100 patients in the UK in a permanent vegetative state (PVS) at any time.

What kind of research was this?

The aim of this study was to investigate ways of improving diagnostic testing for vegetative and minimally conscious states. This built on the researchers’ previous research and has shown it is possible for someone tested using conventional movement responses, and who meets the clinical criteria for being in a vegetative state, to have intact awareness when tested with fMRI.

The researchers wanted to investigate how many patients in a vegetative or minimally conscious state could reliably and repeatedly modulate (alter) their brain activity as shown by their fMRI responses. The researchers say the ability to do this suggests awareness. They also wanted to test if these patients could communicate yes or no responses by modulating their brain activity without training and without the need for movement.

The researchers say that awareness distinguishes minimally conscious patients from those in a vegetative state and has important healthcare, ethical and legal implications.

The usual tests to distinguish between these conditions involves movement responses. However, these methods face several problems, such as muscle weakness, inconsistent responses and a difficulty distinguishing between automatic reflexes and voluntary movement. They say there is a high rate of error (approximately 40%) in the diagnosis in this group of patients.

What did the research involve?

This was an experimental study with cross-sectional analysis in 23 patients in a vegetative state (patients are ‘awake’ in the sense they have sleep-wake cycles, but without detectable awareness) and 31 patients in a minimally conscious state (where patients show inconsistent but reproducible signs of awareness, tested by behavioural responses to stimuli, including the ability to follow commands. However, they remain unable to communicate). 

The patients had all been referred to two hospitals that are major referral centres for this type of brain injury. These hospitals already routinely evaluate brain injury patients with fMRI to assess their performance on motor and spatial imagery tasks.

In this research, two imagery tasks were first tested in 16 healthy control subjects (nine men and seven women) with no history of neurologic disorders. In the motor imagery task, participants were asked to imagine they were playing tennis. In the spatial imagery task, they were asked to imagine walking from room to room in their home and to visualise all that they would ‘see’ if they were there.

Carrying out these tasks stimulates different areas of the brain that can be viewed using an fMRI scanner. For example, the motor cortex area of the brain is responsible for movement, and when a person thinks about movement this will show up on the scan. These tasks were also performed on all of the patients referred.

In a communication task, the control subjects were asked to try to answer questions by thinking about the two tasks. They were asked to think about tennis (motor imagery) for each time they wanted to say yes and about checking the rooms in the house (spatial imagery) if they wanted to say no.

The communication test was given to all healthy controls. It was also given to the one patient who had been able to modulate his brain activity in the first two imagery tasks.

What were the basic results?

Of the 54 patients enrolled in the study, five were able to wilfully modulate their brain activity. Three of these patients demonstrated some sign of awareness in bedside testing, but the other two showed no voluntary behaviour such as movement that could be detected by means of clinical assessment.

One of the patients who was able to wilfully modulate his brain activity was given the communication task. The fMRI scans showed brain activity giving the correct answer to five out of six yes- or no-type questions. The researchers say that it still remained impossible to establish any form of communication with this man.

Among the 23 patients who had been given a diagnosis of being in a vegetative state on admission, four exhibited awareness in the mental imagery tests, suggesting that they had been misdiagnosed.

How did the researchers interpret the results?

The researchers say their results show movement can be so impaired that bedside tests based on the presence or absence of a behavioural response may not reveal awareness, regardless of how thoroughly and carefully they are administered.

They say that in these patients functional MRI complements existing diagnostic tools by providing a method for detecting covert signs of residual thinking and awareness.

Conclusion

These results suggest that some patients, who meet the current criteria for being in a vegetative state, are diagnosed incorrectly and retain thinking and awareness. False-negative (misdiagnoses due to a test being negative when someone has a condition) and false-positive results (misdiagnoses due to a test being positive when someone does not have a condition) are possible with any test. Combining tests can improve their accuracy and it is possible that the combination of bedside tests and fMRI scans would provide improved diagnostic accuracy.

There are some points to note:

• As only one patient in a vegetative state was tested for his communication ability, this will need to be repeated in others to find how many false negatives and false positives this test has. The researchers say that even in healthy volunteers, false negatives when using fMRI imaging are common, and therefore negative findings cannot be used as evidence for a lack of awareness. In this study, negative responses were shown by 49 of the 54 patients and it is not clear if this is due to low sensitivity of the test in detecting awareness, or if the patients were sometimes unconscious during scanning.
• Only five of the six questions elicited a correct response from the patient in a vegetative state, the last question was not answered. The researchers say that they cannot tell from the lack of brain activity if the patient fell asleep, did not hear the question, elected not to answer it or lost consciousness.

The patient in this study and another woman described by the same researchers in 2006, suggest that, though rare, there are cases where people thought to be in a vegetative state are aware to some degree.

This study suggests a method by which some of these non-communicative patients, including those diagnosed as vegetative, minimally conscious, or locked in, may in the future be able to use their residual cognitive capabilities to communicate their thoughts to those around them.

Links To The Headlines

Coma victim talks via brain scanner. Financial Times, February 4 2010

Patient in a vegetative state 'talks' to scientists. Daily Mail, February 4 2010

Think tennis for yes, home for no: how doctors helped man in vegetative state. The Guardian, February 4 2010

Patients in 'vegetative' state can think and communicate. The Daily Telegraph, February 4 2010

Patient 'locked in' by brain injury answers question using thoughts alone. The Times, February 4 2010

Brain scan shows awareness in vegetative patients. BBC News, February 4 2010

Scientist on 'brain scan breakthrough'. BBC News, February 4 2010

I think..I'm alive. The Sun, February 4 2010

Links To Science

Mont MM, Vanhaudenhuyse A, Coleman MR, et al. Willful Modulation of Brain Activity in Disorders of Consciousness. New England Journal of Medicine, February 3 2010

“You don't have to be bipolar to be a genius – but it helps,” according to The Independent. The newspaper said that a Swedish study of over 700,000 adults found that those who scored top grades at school were “four times more likely to develop bipolar disorder than those with average grades”.

This study had strengths, including its large size, good sample selection methods and use of standardised data from national school exams. However, there were some limitations, including the fact that the researchers could not adjust for the influence of some factors that could have affected results, such as family history of bipolar disorder (previously known as manic depression). This means it is possible that some other factors might be behind the link seen.

Although this study suggested that those who achieved the highest grades may be at an increased risk of bipolar disorder later in life, it is important to remember that bipolar disorder is rare, even among high achievers.

Where did the story come from?

Dr James H MacCabe and colleagues from King’s College London and the Karolinska Institute in Sweden carried out this research. The study was funded by the Swedish Council for Working Life and Social Research, and the lead author was supported by the UK Department of Health and the Medical Research Council. The study was published in the peer-reviewed British Journal of Psychiatry.

The Independent and The Daily Telegraph have both reported on this research. Although their coverage is generally accurate, they have reported the risk in terms of relative increases, saying that “clever children are almost four times more likely to suffer from manic depression”. While a four-fold increase in risk may sound large, this does not reflect that the chance of developing bipolar disorder, even for those with higher school achievement, is itself quite low.

What kind of research was this?

This was a cohort study looking at whether there was a link between academic performance in school and the risk of developing bipolar disorder later in life. It looked at academic performance in national exams at age 16 and data on the individuals’ mental health for the next decade. The researchers say that although belief in a link between 'genius' and mental health problems has existed for a long time, few research studies have looked at the possibility of a link.

Cohort studies are good for looking at the link between factors that cannot be studied through randomised controlled trials. This study used data on all individuals who finished compulsory education in Sweden over almost a decade. The size of the dataset available and the fact that it was likely to have included the majority of individuals aged 16 in the country means that the sample is less likely to be biased, and should be a good representation of the Swedish population as a whole.

The data analysed in this study were collected prospectively. This means the figures were recorded as the events occurred, which is preferable to asking people to remember what happened in the past. This practice increases the likelihood that the study’s data are accurate. However, with all studies of this type it is important that researchers take into account factors that could affect the results (potential confounders). In this case, the data used were not originally collected specifically for this study, and therefore may not have recorded some types of information that the researchers might have liked to collect about potential confounders. Having data collected by many different healthcare professionals also means it may not have been collected in the same way for all individuals.

What did the research involve?

The researchers obtained school results for all individuals who finished compulsory education in Sweden between 1988 and 1997. The researchers then looked at the medical records of these people to identify anyone who had subsequently been admitted to hospital for bipolar disorder.

The researchers obtained data for their study from national registries. Information on school performance came from the Swedish national school register, which records this information for all pupils graduating from compulsory education at the age of 16. The researchers say that most pupils with intellectual disabilities or sensory impairments are integrated into mainstream education in Sweden and are therefore included in the register.

The researchers obtained the students’ grades in 16 compulsory subjects, which were based on performance in national examinations sat when they were 16 years old. These exams are graded in a standard way, and the results are combined to give each student a grade point average. Information on admissions to hospital for psychiatric disorders was obtained from the Swedish hospital discharge register, which contains details of hospital stays and diagnoses. Other registers were used to collect information on the individuals’ parents, such as their socio-economic status, education, citizenship and country of origin.

In their analyses the researchers excluded people who had a parent born outside of Sweden as they were more likely to have missing data, and migrant status might have affected the results. They also excluded people who were hospitalised for any psychotic disorder before their exams or in the year after their exams. This left 713,876 individuals, who were followed to December 31 2003. On average, participants were aged 26.5 years at the end of the follow-up period.

The researchers standardised individuals’ school performance using an accepted method that looks at how far away their grade point average is from the average score for their gender. They then analysed the relationship between the overall level of performance in the exams and risk of bipolar disorder. They also looked at the relationship between performance in individual subjects and bipolar disorder, comparing those who got an ‘A’ grade in each subject with those who got ‘B to D’ grades.

The researchers took into account factors that could affect the results (potential confounders), such as gender, season of birth, paternal or maternal age over 40 years at individual’s birth, parental socio-economic status and parental education.

What were the basic results?

During the follow-up period 280 people developed bipolar disorder. This equates to around four people out of every 10,000 people developing bipolar disorder over 10 years.

The researchers found that those people who had excellent grades were just over three times more likely to develop bipolar disorder than people who had average grades in school at age 16 (hazard ratio [HR] after adjustment for potential confounders 3.34, 95% confidence interval [CI] 1.82 to 6.11).

When the researchers looked at men and women separately, the link between better school performance and bipolar disorder was stronger in men, but the difference between the sexes was not statistically significant. People who had the poorest grades in school were also at an increased risk of developing bipolar disorder compared to people with average grades (adjusted HR 1.96, 95% CI 1.07 to 3.56).

When looking at performance in individual subjects, scoring A grades in childcare, Swedish, geography, music, religion, biology, history and civics was linked to an increased risk of bipolar disorder. The link with other subjects was not as strong. Those scoring an A grade in sport were less likely to develop bipolar disorder than those who got B to D grades.

How did the researchers interpret the results?

The researchers conclude that their results “provide support for the hypothesis that exceptional intellectual ability is associated with bipolar disorder”.

Conclusion

This large study suggested that those achieving the highest or lowest grades at school at age 16 were at a higher risk of developing bipolar disorder than students with average performance. There are a number of points to consider when interpreting this research:

• Although the fact that data were collected prospectively increases the reliability of them, some data may be missing, recorded incorrectly or inaccurate.
• Data on diagnoses were based on information recorded at hospital discharge. As the same doctors did not assess all patients, there could have been variation in how bipolar disorder was diagnosed. In addition, any people who had bipolar disorder but had not been hospitalised would not have been identified.
• As with all studies of this type, results may have been influenced by factors other than those assessed. Although the researchers took some of these factors into account, other unmeasured or unknown factors could be having an effect. For example, the researchers did not have information on whether there was any family history of bipolar disorder, or about life circumstances in adult life, and therefore could not take their influence into account.
• The study only followed people to an average age of about 26, a longer follow-up period might show different results.
• It is possible that the link between school performance and bipolar disorder arises because people with higher school achievement or their families are more likely to seek treatment if they experience symptoms of bipolar disorder. However, the authors suggest that this does not seem to be the case, as their previous research found that higher school achievement was associated with reduced risk of schizophrenia and schizoaffective disorder.
• The analysis phase looking at individual subjects was not the main focus of the study and involved multiple statistical tests. This can increase the likelihood of findings occurring by chance, and on this basis, these results should be seen as tentative.

The results of this study do not mean that very high or low school performance actually ‘causes’ bipolar disorder, only that there was an association between the factors in the population studied. One potential explanation suggested by the researchers is that certain aspects of how the brain works in bipolar disorder could also be related to creativity or school performance.

It is important to realise that bipolar disorder is rare, with this study finding that only four cases developed per 10,000 people during a follow-up period of 10 years.

Links To The Headlines

You don't have to be bipolar to be a genius – but it helps. The Independent, February 4 2010

Straight-A schoolchildren at higher risk of bipolar disorder, research claims. The Daily Telegraph, February 4 2010

Links To Science

MacCabe JH, Lambe MP, Cnattingius S et al. Excellent school performance at age 16 and risk of adult bipolar disorder: national cohort study. The British Journal of Psychiatry 2010 196:109–115.

“Surfing the internet can expose a 'dark side' of the soul, with online addicts more likely to be depressed,” the Daily Mail reported. It said that research has found that the worst affected were depressed and addicted “possibly because they are substituting the net for normal social activities”.

This study questioned 1,319 users of social networking sites on their internet use and their depressive symptoms. Although it found an association between the two, this does not prove causation. It’s possible that a person uses the internet more because they are depressed, not the other way around. Other limitations include the fact that only 18 people were ‘addicted’, and the questionnaires assessing their depressive symptoms are not a diagnosis of depression on their own.

A link between depression and internet addiction is not out of the question. There are established links between depression and other addictive behaviours, such as gambling and alcoholism. However, the suggestion of a causal relationship will need further research, as will the implication that social isolation caused by internet addiction might contribute.

Where did the story come from?

The research was carried out by Catriona Morrison and Helen Gore from the Institute of Psychological Science, at the University of Leeds. No sources of funding are reported. The study was published in the peer-reviewed medical journal, Psychopathology.

In general, the news stories represented this study fairly but the strong link reported by several papers is not supported by this single study alone.

What kind of research was this?

This cross-sectional study explored the possibility that internet addiction, like other addictions, may be linked to depression. Internet addiction is defined in this study as “an individual’s inability to control their internet use, which in turn leads to feelings of distress and functional impairment of daily activities”.

A cross-sectional study such as this can only find associations between variables. It cannot prove causation. It is possible that a person will use the internet more often because they have become depressed and withdrawn, not the other way round. A cross-sectional study, provided it is of adequate size, could indicate the prevalence of both depression and internet addiction in the community. However, it would need to examine a representative sample of the population and to have used accurate methods for diagnosing both conditions.

What did the research involve?

For this study, 1,319 people were recruited through advertisements placed on social networking sites. The average age of participants was 21 years (range 16 to 51) and 63% were female. Participants were all users of social networking sites and completed three online questionnaires. They were:

• Young’s Internet Addiction Test, which asks 20 questions to measure a person’s internet use and scores them on a 100-point scale as mildly, moderately or severely addicted.
• The Internet Function Questionnaire, which assesses the nature of their internet use (eg shopping sites, chat, email, research, etc) and the time spent on each.
• Beck Depression Inventory (BDI), which is a well-established self-assessment tool for depression.

The authors then looked at relationships between the internet dependence, types of use and depression.

These are all validated questionnaires. However, as they were all self-completed there is likely to be a degree of inaccuracy introduced.

The researchers were also not able to examine the wider personal, social, professional and health circumstances of participants, which are likely to be the main influence on mental health. In any case, a single questionnaire assessment cannot be taken as a definite diagnosis of addiction or depression.

What were the basic results?

There was a close correlation between addictive tendencies and depression across the sample, with the higher the depression score, the higher the addiction score. Men showed more addictive tendencies than women, and younger people more than older people.

Of the total sample, 18 or 1.2% were considered to have internet addiction. Compared to age- and sex-matched addicted people, the non-addicted group were firmly in the non-depressed symptom range, while those addicted were in the moderate-to-severely depressed range.

There was also a difference in type of internet use, with the addicted group looking at more sexually gratifying websites, gaming websites and online community/chat websites than the non-addicted group.

How did the researchers interpret the results?

The authors conclude that the concept of internet addiction “is emerging as a construct that must be taken seriously” and “those who regard themselves as dependent on the internet report high levels of depressive symptoms”. The authors say that further work is needed on assessing this relationship.

Conclusion

The study has several limitations and cannot prove that using the internet can lead to depression as reported in several newspapers:

• Cross-sectional studies can only investigate associations between variables because they cannot establish the temporal relationship between them, ie which happened first. It is possible that people use the internet more often because they are already depressed and withdrawn, not the other way round.
• The sample was not representative of UK internet users in general. Recruitment took place through social-networking sites, which older people tend not to use, and therefore has sampled a predominantly younger population with an average age of 21.
• Although the study used validated questionnaires to examine the outcomes of interest, all were self-completed so there may be some unavoidable inaccuracy. Also, a single questionnaire assessment cannot be taken as a definite diagnosis of either addiction or depression.
• The study has not been able to examine the wider personal, social, professional and health circumstances of the participants, and it is these factors that are likely to be the main influence on an individual’s mental health.
• Only 18 people were considered to have internet addiction, so examining associations between other factors in this small number of people is likely to involve some inaccuracy.

An association between depression and internet addiction is not out of the question. There are well-established links between depression and other addictive behaviours, such as gambling, drug addiction and alcoholism. However, the suggestion of a causal relationship will need further research, as will the implication that social isolation caused by internet addiction might contribute.

Links To The Headlines

Does being inter the net bring you down loads? Daily Mirror, February 3 2010

Facebook users 'fail to perform at work'. Daily Star, February 3 2010

'Internet addiction' linked to depression, says study. Daily Mail, February 3 2010

'Internet addiction' linked to depression, says study. BBC News, February 3 2010

Links To Science

Catriona M. Morrison, Helen Gore. The Relationship between Excessive Internet Use and Depression: A Questionnaire-Based Study of 1,319 Young People and Adults. Psychopathology 2010;43:121-126