Vitamin D deficiency at birth linked to schizophrenia

Vitamin D deficiency at birth is associated with a significantly increased risk of schizophrenia, according to a new study, confirming a potential way to prevent the disease in the future.

Researcher Professor McGrath, from UQ’s Queensland Brain Institute, told doctorportal: “it’s very unusual that we find risk factors that are so readily treated by safe, cheap and publically accessible interventions.”

“Obviously it’s not a done deal yet. It’s a correlational study and randomised controlled trials need to be done. But we feel we need to keep chasing down this hypothesis.”

The case-controlled study, published in Scientific Reports, included 2602 participants. They were randomly selected from all infants born in Denmark between 1981 and 2000, who received a diagnosis of schizophrenia.

Controls, drawn from the same birth cohort, were individually matched on sex, date of birth and were alive and free of schizophrenia at the time of onset of the matched case. The concentration of 25 hydroxyvitamin D (25OHD) was assessed from neonatal dried blood samples, which have been collected and systematically stored since 1981.

The researchers found that those with 25OHD below 20.4 nmol/L (consistent with standard definitions of vitamin D deficiency) had a 44% increased risk of schizophrenia compared to those in the reference category.

Unlocking an enduring mystery around schizophrenia

Professor McGrath said that researchers have known for a long time – since around 1920 – that people born in winter have a slightly increased risk of developing schizophrenia than those born in other seasons.

“This has always been a bit of mystery. People thought it might have been due to infection and other factors, but we proposed it could be vitamin D, which is mostly known to be linked to bone health.”

Professor McGrath said that most of the work done at the Queensland Brain Institute has demonstrated that if vitamin D is removed from animal models, brain development will be altered.

“That was the hypothesis, so we needed to find a sample. Fortunately, our colleagues in Denmark have access to a biobank, and in 2010 we did a study with this and showed that vitamin D deficiency at birth was linked to an increased risk of schizophrenia.”

“In this new paper, we’ve looked at the research question in a much bigger sample of 2602 and we’ve found exactly the same thing – that babies who have vitamin D deficiency at birth have a 44% increased risk of schizophrenia.

Biological mechanism behind the association is complex and still being probed

“Vitamin D is related to steroid hormones, and we know that if you have steroid hormones you reduce the rate of cell division and you drive cell differentiation.”

New emerging theories relate to the common genetic variants in calcium pathways, which have been shown to increase schizophrenia risk.

“It turns out that vitamin D in many areas of the body, including the brain, alters these exact same channels and we’re exploring that question currently”, Professor McGrath said.

“The problem with vitamin D is that it is one of those hormones which does lots of things to lots of different tissues, so we’ve got a very big sandpit to play in and it will be a challenge to sort out what the mechanisms are.”

Research to tease out a link between vitamin D and other brain disorders

Professor McGrath studies an active area of research: “We have funding from a Danish research agency to measure vitamin D in a very large sample of 80,000 babies and we’ve started that now in Copenhagen, and it will be about two years before those results are ready.”

“We’re looking at whether low vitamin D impacts on other brain disorders. We’ve done some work in the Netherlands a couple of years ago where we measured vitamin D in maternal sera that was taken at 20 weeks of gestation.”

This large study showed that for mothers who had low vitamin D during mid-gestation, their offspring had an increased risk of autism and related symptoms at age 6.

“So we’re wondering whether vitamin D deficiency is just bad for brain development,” Professor McGrath said.

“Most kids that are exposed to vitamin D deficiency are fine – they might have weak bones but most don’t get mental illness. However, we have not been able to reject the hypothesis yet based on epidemiology.”

Smoking fathers, low sperm sons

A new study has linked low sperm count in some men to the fact that their fathers smoked while their mothers were pregnant.

Research has long shown the link between maternal smoking during pregnancy and reduced sperm count in male offspring, but Sweden’s Lund University has now made a link to smoking fathers.

The research team has found that men whose fathers smoked at the time of pregnancy had half as many sperm as those with non-smoking fathers.

This is independent of nicotine exposure from the mother.

News Medical reports that the study was conducted on 104 Swedish men aged between 17 and 20.

“Once the researchers had adjusted for the mother’s own exposure to nicotine, socioeconomic factors, and the sons’ own smoking, men with fathers who smoked had a 41 per cent lower sperm concentration and 51 per cent fewer sperm than men with non-smoking fathers,” the report states.

The research team at Lund University claim discovery of this point and is the first to publish.

Researcher Jonatan Axelsson, specialist physician in occupational and environmental medicine, said he was “very surprised” that, regardless of the mother’s level of exposure to nicotine, the sperm count of the men whose fathers smoked was so much lower.

“Unlike the maternal ovum, the father’s gametes divide continuously throughout life and mutations often occur at the precise moment of cell division,” he said.

“We know that tobacco smoke contains many substances that cause mutations so one can imagine that, at the time of conception, the gametes have undergone mutations and thereby pass on genes that result in reduced sperm quality in the male offspring.

“We know there is a link between sperm count and chances of pregnancy, so that could affect the possibility for these men to have children in future. The father’s smoking is also linked to a shorter reproductive lifespan in daughters, so the notion that everything depends on whether the mother smokes or not doesn’t seem convincing. Future research could perhaps move us closer to a causal link.”

News Medical states: The biomarker cotinine is a metabolite from nicotine which can be measured in the blood. By measuring the level of cotinine, researchers can see whether the parents themselves smoke or whether they have been exposed to passive smoking. Many previous studies have shown that it is harmful to the fetus if the mother smokes but, in this study, the link between the father’s smoking habit and the son’s sperm count is even clearer.

Most newly occurring mutations (known as de novo mutations) come via the father and there are also links between the father’s age and a number of complex diseases. In addition, researchers have observed that smoking is linked to DNA damage in sperm and that smokers have more breaks in the DNA strand. Children of fathers who smoke have been reported to have up to four times as many mutations in a certain repetitive part of the DNA as children of non-smoking fathers.

Call for global bipolar research volunteers

Australian researchers are seeking 5,000 adults who have been treated for bipolar disorder to volunteer for the world’s largest genetic investigation into the chronic illness that can prove devastating.

The Australian Genetics of Bipolar Disorder Study aims to identify the genes that predispose people to bipolar disorder in order to develop more effective, personalised treatments, and ultimately, find a cure for the illness.

QIMR Berghofer Medical Research Institute (QIMR Berghofer) is the base for the Australian arm of the international study, with collaborating centres throughout North America and Europe.

The study aims to recruit 100,000 participants, with Australian researchers hoping to contribute five per cent of the overall study population.

Approximately one in 50 Australians (1.8 per cent) will experience bipolar disorder during their lifetime.

The complex disorder, which occurs commonly in families, typically results from a combination of genetic and environmental influences. Those living with bipolar disorder may be at higher risk of developing other health issues, including alcohol and drug abuse, anxiety, cardiovascular disease, diabetes and obesity. They also carry a 15 times greater risk of suicide than the general population, accounting for up to 25 per cent of all suicides.

Researchers are seeking 5,000 male and female Australian volunteers aged 18 and older, who are currently being, or have been, treated in the past for bipolar disorder. Their involvement will allow researchers to shed light on the genes that predispose people to the illness to ultimately develop more personalised treatments.

Globally, about one in 50 of the population experiences bipolar disorder during their lifetime. In Australia, it is estimated that 1.8 per cent of males and 1.7 per cent of females have experienced bipolar disorder in the previous 12 months.

Participation in the study is free and simple. Volunteers complete a 20-minute online survey, and those who qualify will be asked to donate a saliva sample. Study researchers will analyse DNA from saliva samples to identify specific genes associated with bipolar disorder. The knowledge will be used to improve current, and develop new treatments for bipolar disorder.

Anyone wishing to volunteer for the Australian Genetics of Bipolar Disorder Study should head to www.geneticsofbipolar.org.au, email gbp@qimrberghofer.edu.au or call 1800 257 179.

Standing at desk burns only a few calories

Office workers who opt to stand are likely to burn just nine calories an hour more than their seated colleagues, a study reveals.

Researchers from the University of Bath say their work questions the effectiveness of standing as a strategy to lose weight.

The study, published in the journal Medicine & Science in Sports & Exercise, found standing burnt about nine calories per hour more than sitting – the equivalent of one stalk of celery.

Workers aiming to burn off their morning latte would have to stand for an average of 20 hours.

Dr Javier Gonzalez, from the University of Bath, said: “The very small increase in energy cost of standing compared to sitting that we observed suggests that replacing time spent sitting with time spent standing is unlikely to influence our waistlines in any meaningful way.

“To put this difference in context, it would require an additional 20 hours of standing time, on average, to burn off a medium latte.

“Many people are becoming aware of the negative health effects of prolonged sitting, and so may opt for standing desks.

“These people should be aware that whilst there are still some health benefits to standing more, they should not expect to see drastic changes in their body weight.

“In order to lose body weight, people should focus on increasing physical activity and focus on their diet, too.”

In the study, researchers at Bath and Westmont College in the US tested the resting metabolic rates of 46 healthy men and women.

Participants were then asked to either lie down, sit or stand before measurements were taken of their expired gases to assess calories burned through the activity.

Professor Gregg Afman, of Westmont College, said: “We found that energy cost increase of 0.65 kJ per minute from sitting to standing naturally, which equates to a 12 per cent difference.

“However, current interventions to reduce prolonged sitting like standing desks or wearable technologies only increase standing by a maximum of two hours per day.

“This limited time frame would cause a person to expend less than 20 kcals more each day.”

[Correspondence] Preconception health – Authors’ reply

We thank Lombarte and colleagues for their supportive comments and interesting data on calcium diet in rats, and look forward to the results of their randomised trial. A crucial theme of the second paper1 in our Series was that the origin of adverse offspring phenotype could be traced to periconceptional diet or environmental exposure, hence the need for preconception health. However, we note that in the calcium study2 by Bergel and Belizán in rats, experimental diets lasted for one month before mating to the end of pregnancy; therefore the effects on offspring blood pressure might derive from a broad period of exposure.

Artery hardening begins before high school: Australian study

Only a minority of Australian 12-year-olds have ideal cardiovascular health, research shows, with arterial stiffening evident before some children start high school.

A team from Melbourne’s Murdoch Children’s Research Institute assessed the cardiovascular health of 1028 Australian children aged 11-12 using the seven risk factors of the American Heart Association’s Cardiovascular Health (ICVH) score: physical activity, weight, diet, blood glucose, cholesterol, blood pressure and smoking status.

Only 7% of the children (76) had a perfect ICVH score, and only 39% (406) achieved ideal levels in six out of the seven metrics. The median score was 5/7.

For the first time, the researchers demonstrated that ICVH scores in children were associated with vascular function.

Each additional point in a child’s ICVH score was associated with slower carotid-femoral pulse wave velocity (0.07m/s reduction in pulse wave velocity) and greater carotid elasticity (0.009% per mm Hg).

This relationship was largely mediated by BMI and blood pressure, according to the study published this month in the International Journal of Cardiology.

Study co-author, Professor David Burgner of the University of Melbourne told doctorportal: “If parents were aware that even before their child starts high school, risk factors such as increased BMI and raised BP were already associated with stiffer arteries – which increases the chance of heart attack and stroke as adults – then you’d hope that would galvanise families to try to reduce their risk factors.”

“Cardiovascular disease risk occurs from childhood onwards and we already see associations between risk factors and preclinical changes in the arteries by mid-childhood,” he said.

A family problem

The researchers also assessed 1,235 parents of the children – in most cases the mothers.

The median ICVH score in the parents was lower than in children (4/7), and the association with vascular function was stronger, the study found.

ICVH scores in adults were also linked with changes in vascular structure. Each additional point in an adult’s ICVH score was associated with a smaller carotid intima-media thickness (-7.3μm per metric unit), a measure of subclinical atherosclerosis.

The study found children whose parent had non-ideal health in any of the seven metrics had substantially higher odds for non-ideal health in that metric, for all metrics except physical activity and serum glucose. Children typically did more exercise than their parents.

Ideal diet was the metric least likely to be attained by both adults and children.

Family-based interventions

Professor Burgner said the study highlighted the need for family-based interventions to reduce cardiovascular risk from early on in life.

“Clearly many of the risk factors are shared within families, so considering the family rather than the individual as the unit for interventions that address modifiable environmental risk factors such as increased physical activity or diet may have more impact than just focusing on the adult or child in isolation,” he said.

Professor Burgner said it was unknown whether the poorer vascular function seen in children with lower ICVH scores in the study was reversible.

“The adverse changes in children are smaller than in adults and only relate to the elasticity of the arteries. This likely reflects a longer cumulative exposure to risk factors the older you get,” he said. “Certainly the consensus is that children are physiologically more ‘plastic’, so changes are likely to be reversible, but it is not well understood.”

The study cohort was drawn from the Longitudinal Study of Australian Children and Child Health Checkpoint. The authors cautioned that it was likely to have under-represented socio-economically disadvantaged families.

Dr Richard Liu, another co-author of the study, said that BP measurement should be routine in children. However in practice it was rare.

“Arguably all children with a raised BMI should be screened but it is important that it be done appropriately – that abnormal readings are repeated at least twice, the cuff is appropriately sized and equipment calibrated, and values are measured against established centiles for age, sex and height,” he said.

[Comment] Offline: President Macron—peace needs health

In the Amphitheatre Leroy-Beaulieu-Sorel, located within the Paris Campus of Sciences Po on 27 rue Saint Guillaume, several hundred students gathered last Friday evening to begin their initiation into global health policy making. For the third year running, Sciences Po held a 3-day simulation of the World Health Assembly, the intention being to write a resolution for the agency’s most important governing body. The subject was environmental health. WHO’s Director-General, Dr Tedros, sent a welcoming video message.

The gap isn’t closing

The nation is failing in its efforts to close the health and life expectancy gap between Indigenous and non-Indigenous Australians.

The AMA Indigenous Health Report Card 2018, launched in Brisbane on November 22, scrutinises the 10-year-old Closing the Gap Strategy and concludes that it is unravelling.

The strategy must now be rebuilt, not refreshed, said AMA President Dr Tony Bartone.

One of the strategy’s main targets was to close the life expectancy gap by 2031, but Dr Bartone said it was obvious Australia is not on track to meet that goal.

“Ten years on, progress is limited, mixed, and disappointing,” he said.

“If anything, the gap is widening as Aboriginal and Torres Strait Islander health gains are outpaced by improvement in non-Indigenous health outcomes.

“The strategy has all but unravelled, and efforts underway now to refresh the strategy run the risk of simply perpetuating the current implementation failures.

“The strategy needs to be rebuilt from the ground up, not simply refreshed without adequate funding and commitment from all governments to a national approach.”

Political leadership and increased funding are lacking on the issue, Dr Bartone said.

A refocussing of effort and priorities is needed.

“It is time to address the myth that it is some form of special treatment to provide additional health funding to address additional health needs in the Aboriginal and Torres Strait Islander population,” he said.

“Government spends proportionally more on the health of older Australians when compared to young Australians, simply because elderly people’s health needs are proportionally greater.

“The same principle should be applied when assessing what equitable Indigenous health spending is, relative to non-Indigenous health expenditure.”

The Australian Institute of Health and Welfare estimates that the Aboriginal and Torres Strait Islander burden of disease is 2.3 times greater than the non-Indigenous burden, meaning that the Indigenous population has 2.3 times the health needs of the non-Indigenous population.

This means that for every $1 spent on health care for a non-Indigenous person, $2.30 should be spent on care for an Indigenous person.

But this is not the case, Dr Bartone said. For every $1 spent by the Commonwealth on primary health care, including Medicare, for a non-Indigenous person, only 90 cents is spent on an Indigenous person – a 61 per cent shortfall.

For the Pharmaceutical Benefits Scheme, the gap is even greater – 63 cents for every dollar, or a 73 per cent shortfall from the equitable spend.

“Spending less per capita on those with worse health, and particularly on their primary health care services, is dysfunctional national policy,” he said.

“It leads to us spending six times more on hospital care for Indigenous Australians than we do on prevention-oriented care from GPs and other doctors.”

The Report Card outlines six areas where the Closing the Gap Strategy can be rebuilt.

These include: equitable, needs-based expenditure; implementing health and mental health plans; filling primary health care service gaps; environmental health and housing; addressing social determinants; and placing Aboriginal health in Aboriginal hands.

“We need those leaders, those health leaders in those various communities, to come together with the peak bodies, with the Aboriginal controlled community health organisations, and all the other people as stakeholders in this space to come together to work collaboratively and with common purpose,” Dr Bartone said.

“We will not close the gap until we provide equitable levels of health funding. We need our political leaders and commentators to tackle the irresponsible equating of equitable expenditure with ‘special treatment’ that has hindered efforts to secure the level of funding needed to close the health and life expectancy gap.”

National Aboriginal Community Controlled Health Organisation (NACCHO) welcomed the release of the Report Card and joined the AMA in calling for the Closing the Gap Strategy to be rebuilt from the ground up.

NACCHO Chairwoman Donnella Mills called for the immediate adoption of the Report Card’s recommendations.

“We congratulate the AMA on their work to support closing the gap and endorse the recommendations in the Report,” she said.

“The Report highlights research which indicates the mortality gaps between Aboriginal and Torres Strait Islander peoples and non-Indigenous Australians are widening, not narrowing.

“Urgent and systematic action is needed to reverse these failures and to have any prospect of meeting the Council of Australian Governments’ goal to Close the Gap in life expectancy by 2031.”

The AMA 2018 Indigenous Health Report Card is on the AMA website.

People in cold climates drink more: study

A new study suggests people living in cold climates with less sunlight are more likely to drink heavily.

The US research establishes a link between average temperature and hours of sunlight and alcohol consumption.

Examining data from 193 countries, the group found evidence that climate contributed to a higher incidence of binge drinking and liver disease.

Senior author Ramon Bataller, associate director of the Pittsburgh Liver Research Centre, said: “This is the first study that systematically demonstrates that worldwide and in America, in colder areas and areas with less sun, you have more drinking and more alcoholic cirrhosis.”

Alcohol is a vasodilator, relaxing blood vessels and increasing the flow of warm blood to the skin.

Drinking also is linked to depression, which tends to be more prevalent when sunlight is scarce.

The study, published online in Hepatology, used data from the World Health Organisation (WHO) and the World Meteorological Organisation.

Dr Peter McCann, medical adviser to Castle Craig Hospital, a residential drug and alcohol rehabilitation clinic in the Scottish Borders, contributed to the report.

He said: “We now have new evidence that the weather, and in particular the temperature and amount of sunlight that we are exposed to, has a strong influence on how much alcohol we consume.

“Furthermore this weather-related alcohol consumption is directly linked to our chances of developing the most dangerous form of liver disease – cirrhosis – which can ultimately end in liver failure and death.”

He added: “Stricter laws on alcohol pricing are surely justified when we consider the devastating combined effect of low sunlight and cheaper alcohol on consumption.

“Advertising laws should be addressed with restrictions during winter months strongly considered.”

WILLINGNESS GROWS TO END RHD

BY AMA PRESIDENT DR TONY BARTONE

Rheumatic heart disease (RHD) is a preventable illness affecting about 6,000 Australians, with Indigenous children 55 times more likely to die from the disease than their non-Indigenous peers.

The AMA recognises the role RHD contributes to the widening of the life expectancy gap between Indigenous and non-Indigenous Australians. In 2016, we launched a Report Card on Indigenous Health, A call to action to prevent new cases of RHD in Indigenous Australia by 2031 (target year for ‘closing the gap’ in Indigenous life expectancy).

Our Report Card made a strong statement on the devastating impact of RHD and the importance of new, collaborative strategies to control the disease. Its recommendations included calling for Australian Governments to commit to a target to prevent RHD. It also recommended that governments work in partnership with the Indigenous community to fund and implement a strategy to end RHD.

The Report Card also provided an opportunity for a group of leading health, community, and research organisations to form a coalition END RHD. The purpose of the coalition is to advocate for urgent, comprehensive action on this preventable disease of inequality, and to support those living with the disease and prevent new cases arising.

The founding members of END RHD are the AMA, Heart Foundation, RHD Australia (based at the Menzies School of Health Research), the END RHD Centre of Research Excellence (based at Telethon Kids Institute), the National Aboriginal Community Controlled Health Organisation (NACCHO), the Aboriginal Medical Services Alliance Northern Territory (AMSANT), the Aboriginal Health Council of Western Australia (AHCWA), the Aboriginal Health Council of South Australia (AHCSA), the Queensland Aboriginal and Islander Health Council (QAIHC), and the Aboriginal Health and Medical Research Council of NSW (AH&MRC).

To eliminate rheumatic heart disease in Australia, the coalition calls on the Federal Government to:

guarantee that the Aboriginal and Torres Strait Islander leadership drives the development and implementation of RHD prevention strategies;
set targets to end RHD in Australia;
fund a roadmap to end RHD by 2031;
commit to immediate action in communities at high risk of rheumatic heart disease; and
invest in strategic research and technology to prevent and treat acute rheumatic fever and rheumatic heart disease.

In the two years since the Alliance was formed, END RHD has been working with the communities at risk, securing funding and political will to translate research into action and educating Australians to play a role in ending RHD.

I believe the momentum is growing. RHD was discussed at the COAG meetings in August and October 2018. This has been further helped by the recent commitment from Indigenous Health Minister Ken Wyatt, to a Roadmap to end RHD in Australia, which is due to be completed by early 2019.

There is no doubt that funding is a crucial part of the equation to ending RHD. Recent developments include $3.7m being allocated to five Aboriginal medical services for local community-led pilot Acute Rheumatic Fever (ARF) and RHD prevention programs.

A further $950,000 has been granted to the Telethon Kids Institute to work with the Kimberley Aboriginal Medical Services to establish an innovative END RHD community program focussed on environmental health and local workforce development.

On 23^rd October 2018 an advocacy event at Parliament House, co-hosted by END RHD and the Snow Foundation, where the Government was asked for non-partisan commitment to eliminate RHD in Australia. Minister Wyatt and Shadow Assistant Minister for Indigenous Health Warren Snowden both made commitments in public to tackle RHD as a non-partisan issue. It is an important step for political leaders to acknowledge the seriousness of the problem.

Now, with community-driven change and funding to enable the change, we can hopefully start to bring about the end for RHD in Australia.