White Matter Defects May Lead to Schizophrenia
By Amanda Gardner
HealthDay Reporter
(HealthDay
News) -- Defects in the brain's white matter,
which is responsible for communication between
parts of the brain, may be a key genetic
factor contributing to schizophrenia, a
new study suggests.
"This
is the first clear demonstration of a new
mechanism by which aspects of schizophrenia
and other disorders could be produced,"
said study senior author Gabriel Corfas,
an associate professor of neurology and
otolaryngology at Harvard Medical School.
"On the one hand, this may help us
to understand and start thinking about novel
treatment strategies," added Corfas,
a member of the neurobiology program at
Children's Hospital Boston. "Secondly,
this may help in early detection and, nowadays,
we know that this is critical."
The study also illuminates how two genes
previously linked to schizophrenia actually
contribute to the disease, the researchers
said.
Schizophrenia
is a devastating disease that affects some
1 percent of the world's population. According
to the U.S. National Institute of Mental
Health, people with the disease sometimes
hear voices that aren't there, believe that
others are broadcasting their thoughts to
the world, or become convinced that others
are trying to harm them. These fears can
make patients withdrawn and cause difficulties
when they try to have relationships with
others.
The
causes of schizophrenia aren't clear but,
in the last decade, there's been a growing
awareness that patients with this and other
neuropsychiatric disorders may have defects
in the white matter of the brain.
"Until
now, it was not clear whether the white
matter defects are a cause of the disease
or a result of being treated with drugs
and being sick," Corfas explained.
Also, prior studies had linked schizophrenia
to the genes for neuregulin 1 (NRG1), a
growth factor involved in brain development,
along with erbB4, a receptor on brain cells
through which NRG1 works.
"It was found that if people have particular
variants, the likelihood that they will
have neuropsychiatric disease is enhanced,"
Corfas said. "We had hypothesized for
many years that these genes were important
for formation of white matter, so that brought
together the possibility that maybe these
genes, when they are defective, generate
white matter that is defective and that
causes aspects of neuropsychiatric disorder."
"What we wanted to determine was whether
altering white matter can affect aspects
of the disease," he continued.
Corfas and his team blocked NRG1-erbB signaling
in oligodendrocytes in mice. Oligodendrocytes
are the cells that form the myelin, or fatty
encasing, of nerve fibers. The brain's white
matter is made up of myelinated nerve fibers.
When the signaling was blocked, the mice
had more oligodendrocytes than normal mice,
but the cells had fewer branches and formed
a thinner sheath around the nerve fibers.
This resulted in slower conduction of electric
impulses.
The mice also had alterations in the nerve
cells that make and use dopamine, a brain
chemical that is known to be altered in
people with schizophrenia.
The behavior of the mice was also altered.
"Alterations in signals cause defects,
very specific and relatively subtle in white
matter structure and function, and these
cause dramatic effects on behavior that
are in some ways similar to what you would
expect to see in neuropsychiatric patients,"
Corfas said. "They also involve alterations
in neurochemicals that are known to be altered
in schizophrenia."
The findings are expected to be published
online by the Proceedings of the National
Academy of Sciences during the week of April
23.
Keith
A. Young is associate professor of psychiatry
and behavioral science at Texas A&M
Health Science Center College of Medicine
and co-director of the Central Texas Veterans
Health Care System Neuropsychiatry Research
Program, who recently presented a paper
on this topic at the International Congress
on Schizophrenia Research. He said: "What
they (the study authors) did in this study
was only manipulate this gene or this gene
product in white matter, so it's pretty
clear that the genetic defects that we've
seen in schizophrenia may be being expressed
through the white matter and not other cell
types. They were so specific in genetic
manipulation that it really tightly links
this receptor with myelin deterioration."
But
Young also cautioned that animal models
of schizophrenia are far from perfect.
"In reality, there are no good animal
models of schizophrenia," he said.
"It's just hard to make a rat act like
they're psychotic. It's just such a human
behavior. We don't know if they're delusional.
We don't know if they're hallucinating."
Still,
the new findings are intriguing and could
also have implications for bipolar disorder,
which also seems to involve NRG1 and white
matter defects.
"This
may help identify people who are at risk,"
Corfas said. "The current idea about
schizophrenia is that it's a developmental
disorder, that when we grow up, something
in the way our brains are developed puts
us at risk. Something could make us lose
the balance. It could be drugs. It could
be emotional stress. It could be anything,
so identifying people who are at risk might
help develop the tools and strategies to
protect them."
More
information: Visit the U.S. National Institute
of Mental Health for more on schizophreniae,
(click
here)
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