Mutation of one gene is associated with early onset of psychiatric disorders

The team examined data from 121 people with changes in the GRIN2A gene, which regulates the work of NMDA receptors, the most important molecules that transmit signals between nerve cells. Disorders in this gene are usually associated with epilepsy or developmental delays, but researchers have found that some of its variants are directly related to mental illness. Moreover, in people with such changes, symptoms appear much earlier than usual — already in childhood or adolescence, and not in adulthood, as it happens in most cases.

Of particular interest was the fact that some of the patients had exclusively psychiatric manifestations, without neurological disorders. This showed that the GRIN2A defect is able to trigger the disease on its own, without other genetic or external triggers. This finding changes the understanding of the mechanisms of mental illness development and may lead to new diagnostic methods.

The work has a therapeutic continuation. In collaboration with Heidelberg clinicians, the researchers tested the treatment with L-serine, a safe amino acid that activates NMDA receptors. Some patients with GRIN2A mutations showed a marked improvement in mental symptoms during therapy, which opens up the prospect for developing personalized treatment.

The results were made possible thanks to the international registry of patients with GRIN2A mutations, which Professor Johannes Lemke’s team has been collecting for almost 15 years. Now scientists hope that further research will help to better understand how single genetic changes can lead to serious mental disorders — and how these processes can be changed.