August 12, 2004

Glutamate Affects SZ Traits

Read more... Schizophrenia Biology

Researchers at the National Institute of Mental Health released findings that link one small section of one gene - which codes for the neurotransmitter glutamate - with many schizophrenic traits. The gene GRM3 normally regulates the amount of glutamate neurotransmitter that is released into nerve synapses during cell-to-cell communication. Scientists hypothesize that an abnormally functioning GRM3 releases an improper amount of glutamate in the brain, affecting cognition and raising the risk for schizophrenia.

"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.

Previous research has already identified many candidate genes that likely contribute to the onset of schizophrenia, and some of these also affect the glutamate system.

Glutamate is a neurotransmitter that plays a role in brain cell communication - chemical signaling between nerve cells.

This recent study focuses on one section of the GRM3 gene - a sequence of code that may differe by just one base pair (the "letters" of the genetic code) in patients affected by schizophrenia. According to the data, people with schizophrenia are more likely to have a gene variant with the base "A" (adenine) in this crucial spot, rather than a sequence with the letter "G" (guanine). Study results also showed that people inheriting this "A" variant have lower levels of glutamate in their brains, and scored less well on cognitive tests than those with the "G" variant.

Having this GRM3 variant does not cause schizophrenia - rather, scientists hypothesize that people with a G in this sequence have a higher level of cognitive protection, and are less likely to develop schizophrenia symptoms in response to other, undetermined events. Paradoxically, the gene sequence including the higher risk "A" base is more common among humans. The reason for this is currently unknown.

For the full article, see "Schizophrenia Gene Variant Linked to Risk Traits" (Aug 11 2004) in NIH News (

For more research linking glutamate function to schizophrenia symptoms, see the following:

1) Glutamate paths surface in schizophrenia (Sept 8, 2001) - Science News article.

2) June 20 NewsBlog entry - Glutamate levels elevated in teens at-risk for schizophrenia.


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