Schizophrenia :: Gene, glutamate associated with schizophrenia

Researchers at the NIH’s National Institute of Mental
Health (NIMH) have identified a relationship between a
small section of one gene, the brain chemical messenger
glutamate, and a collection of traits known to be
associated with schizophrenia.

The finding confirms the
gene responsible for management of glutamate is a promising
candidate in determining risk for schizophrenia. The study,
conducted by Michael Egan, M.D., Daniel Weinberger, M.D.,
and colleagues, is published in the
“Proceedings of the National Academy of Sciences”.

Glutamate is a key neurotransmitter long thought to play a
role in schizophrenia. The gene identified in this study
makes the glutamate receptor (GMR3) which is responsible
for regulating glutamate in synapses – spaces in between
brain cells – where chemicals like glutamate transfer
information from cell to cell. The amount of glutamate
remaining in the synapse may have a downstream impact on
cognition.

“Because of the small effects of individual genes in
complex genetic disorders like schizophrenia, it is
difficult to make significant associations with any one
particular marker. However, this study brings us closer to
unlocking the genetic clues that increase the risk for
schizophrenia,” said NIMH Director Thomas R. Insel, M.D.

Researchers know that schizophrenia affects several regions
in the front part of the brain that are involved in higher
order thinking and decision-making and neurotransmitter
systems like glutamate. Many of the genes already
identified as likely candidates for the disorder have been
thought to affect the glutamate system. The study
implicates the GMR3 gene as well.

GRM3 alters glutamate transmission, brain physiology and
cognition, increasing the risk for schizophrenia. To
pinpoint the section of the gene responsible for these
changes, scientists are exploring a region where the gene
may differ by one letter at a location called SNP4. The
normal variation is spelled with either an ‘A’ – the more
common of the two – or a ‘G’. Patients with schizophrenia
are more likely to inherit an ‘A’ from either parent,
indicating the ‘A’ variant slightly increases risk. The ‘A’
variant is also associated with the pattern of traits
linked with the disorder. This was true in patients, their
healthy siblings, and normal volunteers.

People with schizophrenia and their healthy siblings share
the inefficient brain physiology, and cognition patterns,
which suggests a link to genetic risk, though the disease
itself is most likely caused by a combination of genetic
and environmental factors. The gene seems to affect the
mechanism of memory encoding only as there was no genotype
effect seen during retrieval in the memory tests.

Although scientists could not be certain that the ‘A/G’
difference accounts for all the affects on brain function,
there may be yet undiscovered variations located near SNP4
on the GRM3 gene. It is unclear as to why the higher-risk
‘A’ variant is more common in humans. Researchers speculate
that it may provide a counterbalancing advantage, perhaps
related to reduced glutamate in the cells.


Leave a Comment