Early life vitamin D linked to optimal brain development
After decades of research into the causes of serious mental disorders, Professor John McGrath is preparing to retire. But he’s not going quietly.
The esteemed psychiatrist and epidemiologist, who has devoted much of his career to uncovering modifiable risk factors for schizophrenia and related conditions, published a study that provides new evidence linking low prenatal vitamin D to increased risk of schizophrenia, autism, and attention deficit/hyperactivity disorder (ADHD).
In 1999, Professor McGrath published his first paper proposing a link between prenatal vitamin D deficiency and schizophrenia. What began as a speculative idea would spark a decades-long body of work, carried out with collaborators across Australia, Denmark, the Netherlands, and Sweden.
"We've long known that those born in winter and spring have a slightly higher risk of schizophrenia.
“About 25 years ago, I proposed that low neonatal vitamin D might be underlying this seasonal finding. In collaboration with my colleagues from UQ's Queensland Brain Institute (QBI), we began the long journey from animal models to humans to discover how developmental vitamin D deficiency impacted on brain functioning.”
From hypothesis to global research
The findings gained momentum in the early 2000s, with innovative assays developed at QBI in collaboration with Professor Darryl Eyles. This discovery enabled Professor McGrath’s team to measure vitamin D in 20-year-old archived dried blood samples - samples so small they resemble bits of paper confetti.
They started with a small cohort—400 individuals with schizophrenia and 400 controls—and found that those who developed schizophrenia had significantly lower vitamin D levels at birth. A follow-up study with 2,600 samples confirmed the finding.
But Professor McGrath didn’t stop there. In partnership with researchers in the Netherlands, he extended the investigation to autism. Using blood serum from the large Generation R cohort in Rotterdam—comprising over 8,000 participants—he and his colleagues found evidence linking low prenatal vitamin D was associated with increased risk of autism-related symptoms.
The foundation for much of this research came through partnerships with Aarhus University in Denmark, where Professor McGrath later received the prestigious Niels Bohr Professorship in 2016, funded by the Danish National Research Foundation.
Landmark study: 71,793 samples analysed
The Niels Bohr professorship allowed the mental health researcher to pursue what he calls his “dream project”: measuring vitamin D levels in tens of thousands of individuals using neonatal blood samples stored in Danish health registries.
Denmark, remarkably, retains dried blood spots taken at birth for nearly all citizens—millions of samples that have become a treasure trove for epidemiological research.
“The culmination of this work is this latest paper, which has been a large-scale analysis of 71,793 neonatal samples, completed during my Niels Bohr Professorship and the results were striking,” he commented.
“We used our original assay to measure the main storage form of vitamin D (25 hydroxyvitamin D) and also measured the concentration of vitamin D binding protein.
“The sample had previously also analysed the babies’ DNA – so we could also explore the link between gene variation associated with vitamin D and the risk of mental disorders."
These converging lines of different types of evidence strengthen the hypothesis that low neonatal vitamin D is a risk factor for neurological disorders such as schizophrenia, autism and ADHD.
Potential for prevention
While careful to note that the new findings are correlative and not definitive proof that low vitamin D causes an increased risk of neurodevelopmental disorders, Professor McGrath emphasises that his team used multiple methods—including genetic analyses—to triangulate evidence.
His latest models suggest that ensuring adequate prenatal vitamin D could potentially prevent 15% of schizophrenia cases, 9% of ADHD, and 5% of autism spectrum disorder in the Danish population. He urges adherence to national health guidelines on vitamin D supplementation during pregnancy, particularly in higher-latitude countries like Denmark, where sunlight is often scarce.
“This latest finding could have important public health implications,” he said.
“Just as folate supplement can reduce the incidence of spina bifida, our data suggests that vitamin D may reduce the incidence of three disabling mental disorders. Vitamin D is a safe, cheap, and widely available supplement.”
His dedication to exploring modifiable risk factors for mental illness has earned him international acclaim. His accolades include the Lieber Prize for Outstanding Achievement in Schizophrenia Research (2019), the Premier’s Award for Medical Research, the Centenary Medal, and appointment as a Member of the Order of Australia.
But the Niels Bohr Professorship gave him the time and resources to complete his most ambitious research.
“It’s a lovely way to finish my career,” he quipped. “I’ve devoted my research career to understanding risk factors for mental health disorders and, in particular risk factors that were potentially modifiable.
“That is the holy grail for researchers - we want to find ways to prevent mental disorders.
“The overall body of research that we have done here at QBI, and in collaboration with international researchers, provides evidence suggesting that optimal vitamin D during early life is not only important to build strong bones, but also to build healthy brains.”
Read the media release.
Professor John McGrath will be the guest speaker at the QBI Brain Research Endowment Fund dinner on 5 June at the Emporium Hotel, South Bank, Brisbane.
Register here for tickets.
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