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Until now, researchers assumed that schizophrenia, anxiety disorders or depression arise from an interplay of many different factors, including genetic ones. An international study led by the Institute of Human Genetics at the University of Leipzig Medical Center has now demonstrated for the first time that changes in a single gene can in fact cause a mental illness. The new research has just been published in the renowned journal Molecular Psychiatry.
According to the World Health Organization (WHO), in 2021 almost one in seven people worldwide was living with a mental illness, with anxiety disorders and depression the most common. Mental disorders typically have complex causes with a major genetic component. Having a close family member who is affected is regarded as one of the greatest known risk factors. Previous studies assumed that mental disorders arise against the background of numerous genetic factors.
“Our current findings indicate that GRIN2A is the first known gene that, on its own, can cause a mental illness. This distinguishes it from the polygenic causes of such disorders that have been assumed to date,” says Professor Johannes Lemke, lead author of the study and Director of the Institute of Human Genetics at the University of Leipzig Medical Center.
In the present study, data from 121 individuals with a genetic alteration in the GRIN2A gene were analysed statistically. “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 striking is that, in the context of a GRIN2A alteration, these disorders already appear in childhood or adolescence – in contrast to the more typical manifestation in adulthood,” says Professor Lemke. What the human geneticist and his research team found particularly noteworthy in the study’s results was that some affected individuals showed exclusively psychiatric symptoms. GRIN2A alterations are otherwise typically associated with conditions like epilepsy or intellectual disability.
The GRIN2A gene plays a central role in regulating the electrical excitability of nerve cells. In the present study, certain variants led to reduced activity of the NMDA receptor, a key molecule in signal transmission in the brain. Together with Dr Steffen Syrbe, Professor at the Heidelberg Medical Faculty and paediatric neurologist at Heidelberg University Hospital, the clinicians showed that this aspect could also be therapeutically relevant: in an initial treatment series, patients showed marked improvements in their psychiatric symptoms following therapy with L-serine – a dietary supplement that activates the NMDA receptor.
Professors Johannes Lemke and Steffen Syrbe have been working together for almost 15 years, in both research and clinical practice, on disorders of the glutamate receptor in the brain in children with neurological diseases. During this time, Professor Lemke has established an international registry that comprises the world’s largest cohort of GRIN2A patients, which formed the basis for the current publication.
Translation: Matthew Rockey
Professor Johannes Lemke
Director, Institute of Human Genetics
Phone: +49341 - 97 23800
Email: Johannes.Lemke@medizin.uni-leipzig.de
Original publication in Molecular Psychiatry: GRIN2A null variants confer a high risk for early-onset schizophrenia and other mental disorders and potentially enable precision therapy. Doi: https://doi.org/10.1038/s41380-025-03279-4
In the present study, data from 121 individuals with a genetic alteration in the GRIN2A gene were an ...
Quelle: Symbolbild: Colourbox
Prof Johannes Lemke
Quelle: Stefan Straube
Copyright: UKL
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Journalisten, jedermann
Medizin
überregional
Forschungs- / Wissenstransfer, Forschungsergebnisse
Englisch
In the present study, data from 121 individuals with a genetic alteration in the GRIN2A gene were an ...
Quelle: Symbolbild: Colourbox
Prof Johannes Lemke
Quelle: Stefan Straube
Copyright: UKL
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