Schizophrenia Predicted by a Gene Variant

Medical Authors and Editors: Barbara K. Hecht, Ph.D. and Frederick Hecht, M.D.

Aug 13, 2004 -- A gene that influences the management of a messenger molecule called glutamate has been found to be a leading candidate for predicting the risk of schizophrenia. The gene known as GRM3 encodes the glutamate receptor. It regulates glutamate at the synapse, the space between neurons in the brain, where glutamate is a transmitter of information from one neuron to the next.

These findings were published online by Michael Egan and colleagues at the National Institute of Mental Health and will appear in print in the August 24th issue of the prestigious Proceedings of the National Academy of Sciences (PNAS).

Schizophrenia and GRM3

Schizophrenia affects several regions in the prefrontal cortex (the front part of the brain) that are involved in cognition including the processes of higher thinking and decision-making. Many of the genes already identified as likely candidates in schizophrenia affect the glutamate system. This study implicates the GRM3 gene.

GRM3 alters glutamate transmission, cognition, and increases the risk for schizophrenia. To pinpoint the section of GRM3 responsible for these changes, a region where the gene may differ by one letter at a location called SNP4 was studied. Normal variants of GRM3 are spelled with an A or, less often, a G.

The A Variant of GRM3

People with schizophrenia were found to be more likely to have the A variant. In other words, the A variant increases the risk of schizophrenia. People with the A variant have lower levels of the chemical that promotes gene expression for the protein responsible for regulating the level of glutamate in the cell. A measure of cell health (called N-acetylaspartate) was lower in people with the A variant. People with the A variant also had poorer performance on several cognitive tests of prefrontal function.