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Researchers at The University of Western Australia and Telethon Kids Institute have found vitamin D plays an important role in the brain development of children.
Vitamin D is not readily available in the diet, and mainly comes from exposure of the skin to sunlight and the effects of ultraviolet B radiation.
The study, which will be published tomorow (Wednesday 21 March) in the Journal of Endocrinology, found female rats with low levels of vitamin D during pregnancy and lactation were more likely to have offspring that displayed unusual brain development. It is believed this can lead to autistic-like behaviour later in life, including characteristics such as reduced social interaction and impaired memory and learning.
Dr Caitlin Wyrwoll and colleagues at The University of Western Australia found rats born to vitamin D deficient mothers displayed altered social behaviour in adulthood.
”Differences in social behaviour are a hallmark of numerous human conditions, such as autism spectrum disorder (ASD), and these findings provide further evidence of the importance of maternal vitamin D levels during pregnancy in the brain development of offspring,” Dr Wyrwoll said.
ASD is a lifelong condition that ranges in severity and impacts how individuals interact and communicate. Epidemiological studies have found that lower levels of maternal Vitamin D during pregnancy are associated with an increased risk of ASD. However, biological mechanisms underpinning this relationship remain unclear.
”We found the rats with a vitamin D deficiency in early life displayed altered social behaviours, altered brain chemistry and impaired cognitive functioning,” Dr Wyrwoll said.
”For example offspring of vitamin D deficient mothers had less interest in interacting with a unfamiliar rat, compared to those who had mothers with healthy levels of vitamin D.”
Dr Wyrwoll said the researchers also conducted memory tests, including an object recognition test.
”The ability to differeniate between familiar and new objects was much lower in those rats with vitamin D deficiency in early life,” she said.
Dr Wyrwoll said although the study focused on rats, the data indicated vitamin D levels during pregnancy were important for brain development, and may point to a contributing factor in the development of neurodevelopmental conditions such as ASD.
”However further work is needed to establish whether these associations apply to humans,” she said.
Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Professor Darryl Eyles is Head of the Queensland Centre for Mental Health Research Developmental Neurobiology Laboratory at the University of Queensland
The origins of all complex psychiatric conditions such as autism remains unknown. There are multiple genetic and environmental factors that combine to increase an individual’s risk.
Recently, vitamin D deficiency has been receiving experimental attention as several groups have begun to report maternal deficiency leads to a small but significant increased risk of autism in children.
In order to understand the neurobiology behind this relationship, we require experimental animal models.
Very recent preclinical data indicates that maternal vitamin D deficiency induces alterations in behavioural phenotypes [observable behavioural characteristics] of interest to autism researchers, such as alterations in pup/dam communication, impairments in social interaction or alterations in stereotyped movements.
Other studies have shown the administration of either dietary vitamin D or the vitamin D hormone prevent the onset of such phenotypes in other animal models of relevance to autism.
The study by Wyrwoll and colleagues is the latest in an emerging number of such preclinical studies which are helping to build a case for public health interventions. A notable contribution from this paper is the suggestion that maternal behaviour in relation to rat pups may also be altered.
Vitamin D supplementation is already recommended during pregnancy in Australia, however, the levels may be too low to be of benefit.
Given vitamin D is safe and cheap, it may be time to reconsider its use in pregnancy, especially in situations of either deficiency or the presence of known autism risk modifiers i.e. infections during pregnancy.
Professor Ulrich (Ulli) Schall is Director of the School of Medicine and Public Health at The University of Newcastle
This is a well-designed study which is comprehensively demonstrating the neural effects of perinatal maternal vitamin D deficiency in rats. It is well known that vitamin D plays an important role in brain development.
Any deficiency is therefore likely to increase the risk for so called 'pervasive' or 'neurodevelopmental' disorders, such as autism or schizophrenia.
However, 'risk' means that the developing brain is more susceptible for these conditions, rather than that the vitamin D deficiency is 'causing' it.
Other factors such as a genetic predisposition and life events have also shown to increase risk but can also facilitate resilience. Notwithstanding, perinatal vitamin D supplementation is an important public health measure for vitamin D-deficient populations.
Dr Edwin Lim is a Senior Research Fellow in the Department of Biomedical Sciences at Macquarie University
This is a very interesting finding and it ties in nicely with some of our previous works looking at brain metabolism.
Vitamin D can activate a biochemical pathway responsible for fetal development known as the kynurenine pathway which produces a compound known as Nicotinamide Adenine Dinucleotide (commonly known as NAD). This compound not only provides protection to the brain against oxidative stress (i.e. aging) but also promotes cellular growth. This is important because levels of vitamin D and NAD production may be linked during pregnancy.
What this mean is that lower maternal vitamin D may result in lower NAD production during pregnancy, compared to those who have a normal vitamin D level. This is consistent with what we see in our previous study, published last year in the New England Journal of Medicine, that defective genes to this biochemical pathway can reduce NAD production responsible for brain development.
Our earlier study also showed that this biochemical pathway (i.e. kynurenine pathway) is perturbed in autism. Further work will be needed to demonstrate the link between maternal vitamin D and changes to the kynurenine pathway and NAD levels during fetal development relevant to autism.
Professor Robyn is Director of Autism Research Initiative at Flinders University
The link between Vitamin D deficiency and ASD has long been speculated. Magnusson et al (2016) did a very comprehensive adult study in Sweden. They found that a vitamin D deficiency which is rare (<01 per cent of population even in Sweden) is:
...strongly associated with socioeconomic and medical parental characteristics (Table 1) including maternal psychiatric disorders, but not with preterm or small for gestational age births. Diagnosed lifetime maternal vitamin D deficiency was associated with risk of ASD and, in particular, of ASD with intellectual disability (p for homogeneity 0.17) (Table 2), although there was some attenuation upon adjustment for parental characteristics.
Which means there may be a slight link. However, vitamin D deficiency could not be randomly allocated, and given it is also linked to other factors such as low SES, the link may not be direct. Also, given that this is so rare it cannot account for the majority of people with ASD.
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