Australian researchers have produced the
first compelling evidence that low prenatal vitamin D might be a
risk factor for schizophrenia. They have shown that the brains of
vitamin D-depleted neonate rats have proportionally thinner
cortices and larger ventricles than undepleted controls - changes
that are also seen in the brains of schizophrenics.
The group, led by John McGrath of the Queensland Centre for
Schizophrenia Research in Wacol, recently verified that levels of
cell mitosis in schizophrenic brains are raised. Its new,
unpublished work shows that mitosis is also elevated in the
dentate gyrus, basal ganglia and hypothalamus of the vitamin
D-deficient rats.
In behavioral studies these rats showed a reduced pre-pulse
inhibition (PPI) to acoustic startle - the degree to which a low
pulse of sound preceding a loud test pulse inhibits their startle
reaction to that test pulse. Reduced PPI is regarded as the gold
standard test of animal models of schizophrenia.
And the first clues to the mechanisms by which vitamin D might
be influencing brain development have become evident, according to
the team's developmental neurobiologist Alan Mackay-Sim of the
Centre for Molecular Neurobiology at Griffith University in
Nathan, Queensland.
"We get big changes in nerve growth factor levels and
receptors," Mackay-Sim told BioMedNet News.
Gene array analyses found that vitamin D depletion altered the
expression of a vast number of genes - the majority being
downregulated. Among them are genes regulating neurotransmission,
cell cycle control, cell trafficking and the cytoskeleton.
Many of the genes matched those found to be altered in similar
gene array studies of post-mortem tissue from schizophrenic
brains.
Vitamin D synthesis in the body is triggered by UVB light. But
until a few years ago it was thought to play no role in the brain.
When McGrath put forward his controversial theory, in 1999, he
argued that it could help to explain why the incidence of
schizophrenia was higher among those born in the winter and
spring, and among dark-skinned immigrants to northern countries.
What the new research shows, says Mackay-Sim, is that vitamin D
has a broader significance for brain development: "It's
having profound effects on the brain which could lead to more than
just schizophrenia, because schizophrenia is only operating in
[genetically] susceptible individuals."
And depletion until birth, later corrected, can have
long-reaching effects into adulthood, he adds.
Sandra Rees of the Department of Anatomy and Cell Biology at
the University of Melbourne, who studies schizophrenia and early
brain development, says she looks forward to seeing confirmation
of the findings.
Rees' own group has shown that a number of insults occurring
during development can lead to enlarged ventricles in the brains
of adolescent guinea pigs, including hypoxia and malnutrition.
So Vitamin D depletion may not turn out to be the only culprit.
However, says McGrath, when you take into account that
large-scale studies in the US have suggested up to 12% of women of
childbearing age are vitamin D-deficient, the implications of his
research are enormous. "If they were children, they would
have rickets," he noted.
The incidence of schizophrenia in the population is about 1 in
100.
