According to the World Health Organization (WHO), almost one in seven people worldwide were living with a mental illness in 2021, with anxiety disorders and depression being the most common. These conditions often arise from a combination of influences, and genetics plays a large role in shaping a person’s risk. Having a close family member with a mental illness remains one of the strongest known predictors. Until recently, research suggested that psychiatric disorders typically develop from the combined effects of many different genes.
“Our current findings indicate that GRIN2A is the first known gene that, on its own, can cause mental illness. This distinguishes it from the polygenic causes of such disorders that have been assumed until now,” says Professor Johannes Lemke, senior author of the study and director of the Institute of Human Genetics at the Leipzig University Medical Center.
Study links GRIN2A variants to early-onset psychiatric symptoms
In this research, the researchers performed a statistical analysis of data from 121 individuals who carried a genetic change in the GRIN2A gene. “We were able to show that certain variants of this gene are associated not only with schizophrenia but also with other mental illnesses. What is surprising is that, in the context of a GRIN2A alteration, these disorders already appear in childhood or adolescence, unlike the more typical manifestation in adulthood,” says Professor Lemke. The research team also highlighted an unexpected finding: some participants only showed psychiatric symptoms, although changes in GRIN2A are often related to epilepsy or intellectual disability.
How GRIN2A affects brain signaling and a possible treatment approach
The GRIN2A gene helps regulate the activity of nerve cells by influencing their electrical signaling. In this study, certain genetic variants reduced the function of the NMDA receptor, a key component involved in communication between brain cells. In collaboration with Dr. Steffen Syrbe, professor at Heidelberg Medical School and pediatric neurologist at Heidelberg University Hospital, the team showed that this reduced activity may be medically important. In an initial treatment effort, patients experienced notable improvements in psychiatric symptoms after receiving L-serine, a dietary supplement that activates the NMDA receptor.
Professors Johannes Lemke and Steffen Syrbe have collaborated for almost 15 years in clinical and research settings to better understand disorders affecting the brain’s glutamate receptor in children with neurological conditions. During this period, Professor Lemke established an international registry containing the largest known group of GRIN2A patients worldwide, laying the foundation for the findings published in this study.
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