Researchers have identified GRIN2A as the first gene proven to directly cause mental illness, marking a major shift in understanding conditions long believed to stem only from many genes acting together.
The study found that certain GRIN2A variants trigger psychiatric disorders earlier than usual, often in childhood or adolescence, and in some cases appear without the epilepsy or intellectual disabilities typically linked to this gene.
Mental illness affects nearly one in seven people globally, and while genetics is a strong predictor, research has largely focused on polygenic risk. Professor Johannes Lemke, lead author and Director of Human Genetics at the University of Leipzig Medical Center, said the findings overturn previous assumptions: GRIN2A is the first gene shown to cause psychiatric illness independently.
The study analyzed data from 121 individuals with GRIN2A variants and found strong links to schizophrenia and other psychiatric conditions, with earlier onset patterns being especially notable. Unexpectedly, some patients displayed only mental health symptoms, suggesting the gene's impact is broader and more variable than previously understood.
GRIN2A influences the brain's NMDA receptor, which is critical for communication between nerve cells. Certain harmful variants weaken receptor function, a discovery made in collaboration with Dr. Steffen Syrbe of Heidelberg University Hospital. Early treatment observations showed that L-serine, a supplement that activates NMDA receptors, helped improve psychiatric symptoms in affected patients.
The results build on more than 15 years of joint clinical and research work by Lemke and Syrbe, including the creation of the world's largest GRIN2A patient registry, which enabled this breakthrough.
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