UQ team links vitamin D deficiency with schizophrenia, MS

Scientists at the University of Queensland have linked maternal vitamin D deficiency in pregnancy to abnormal foetal brain development and an increased the risk of behavioural problems, schizophrenia and multiple sclerosis (MS) later in life.

Vitamin D is synthesised in the skin under moderate exposure to ultraviolet-B radiation in sunlight, but can be supplemented through the diet.

Dr Darrel Eyles, of UQ's Centre for Mental Health Research, believes his team's research into the effect of low developmental vitamin D on brain development helps explain why:

• Multiple sclerosis is almost unknown in tropical latitudes.
• The incidence of schizophrenia and MS increases steadily in a polewards direction.<.li>
• Individuals born in winter and spring are at higher risk of schizophrenia and MS.
• Females have about at twice the risk of developing MS as males.

Eyles told the Australian Neuroscience Society conference in Sydney last week his research team now has physiological evidence from a rat model of developmental vitamin D deficiency to support its hypothesis,

He said he became interested in the subject of non-genetic risk factors for schizophrenia while working with Prof John McGrath, an epidemiologist.

"Plenty of people are turning up candidate risk genes, and when we asked what the non-genetic factors might be, we hit upon vitamin D deficiency," Eyles said. "For 70 years, we've known that babies born in winter and spring are at increased risk of psychiatric disorders later in life. The effect is only small, but it's rock-solid around the world. "We suspected it might be a lack of maternal vitamin D in winter and spring, because people who were born in summer are much less likely to develop schizophrenia and MS."

Relative risk

Schizophrenia and MS, an autoimmune disorder that attacks the fatty, insulating sheath around neurons in the brain, both showed a very tight latitudinal gradient across Australia.

"The relative risk of someone in Darwin developing MS is very low, and as you step southwards through the state capitals, the risk factors increase, peaking a 7 per cent increased risk of people in Hobart getting MS," Eyles said. "It became my job to work out biologically what vitamin D was doing for the brain, and specifically, for the developing brain."

Eyles said that, among other things, rats born to vitamin D-deficient mothers showed an increased in the size of the lateral ventricles, and abnormalities in dopamine signalling.

"The brain is slightly less developed, and not quite fully differentiated, which wasn't unexpected, because vitamin D is required for the differentiation of all organs," he said. "So brain development is affected by vitamin D deficiency.

"There's also a slight decrease in cell elimination as the brain develops -- pups that develop in a maternally depleted environment have more cells. The cortex is compacted and slightly thinner, correcting for the larger size of the brain.

"We plan to analyse the consequences of that, but at present, our model simply involves removing vitamin D during development."

He said the rat pups grew up with normal calcium and thyroid metabolism, but exhibited hyperkinetic behaviour characteristic of dopamine deficiency, similar to the restless behaviour of human schizophrenics. "They also behaved very abnormally when we gave them psychomimetic drugs to replicate the symptoms of psychotic behaviour, and responded very abnormally when we treated them with anti-psychotics."

Normal development

Eyles said a PhD student, Joss O'Loan, had devised an experiment in which the vitamin D-depleted female rats were given vitamin D supplements within 12 hours of conception. All the abnormal behaviours in the pups disappeared, and they had normal brain development.

Eyles said the increased risk of schizophrenia and multiple sclerosis in higher latitudes correlates with shorter day lengths in winter and spring at higher latitudes, and decreasing exposure to UV-B wavelengths in sunlight.

Fortunately for Tasmanians, dietary amelioration is readily available not far offshore: deep-sea, coldwater fish are rich in vitamin D.

"It's interesting that coldwater fish became a dietary staple for humans who migrated into the northerly latitudes of Europe in prehistoric times, because they couldn't get vitamin D any other way," Eyles said. "Dietary vitamin D allowed humans to colonise the planet."

Eyles said rickets, a bone disorder resulting from impaired calcium metabolism induced by vitamin D deficiency, is now re-emerging as a health problem in Australia and manufacturers of dairy products and margarine now fortify these foods with vitamin D. He said fortification of foods with vitamin D could lead to similar health benefits to the practice of fortifying breakfast cereals and some other foods with folate, to avoid neural-tube defects in pregnancy.

Vitamin D supplementation is very safe, Eyles said, even in pregnancy. "There's definitely a health message from our work. In the case of MS, we're extraordinarily convinced [of the link to vitamin D deficiency]. If we're right, supplementation would enormously reduce the burden of disease, which would be wonderful."

Danish donors

On the day after the neuroscience conference, Eyles left for Denmark to explore a potentially valuable resource that could confirm their hypothesis. The Danes have maintained archive of dried blood samples, taken from every newborn, which extends back 30 years. The donors of the earliest samples are now well into adulthood.

Eyles will test the samples for metabolites of vitamin D, to assess whether the babies were exposed to maternal vitamin D defiency due to low sunlight levels in winter and spring, and then correlate the results with rates of schizophrenia and MS in the adult cohort.