For the First Time, Mutations in a Single Gene Have Been Linked to Mental Illness

A team of physicians specializing in genetics and neurology discovered that mental illnesses such as schizophrenia are closely linked to mutations in the GRIN2A gene. The scientists mantain that identifying this genetic risk factor opens up the possibility of designing preventive therapies in the future.

The GRIN2A gene regulates communication between neurons by producing the GluN2A protein. When functioning optimally, it promotes the transmission of electrical signals between nerve cells and facilitates essential processes such as learning, memory, language, and brain development.

In their article, published in Molecular Psychiatry, the researchers demonstrated that the gene mutation reduces the activity of the NMDA electrical receptor, which aids in neuronal communication, thereby increasing the risk of developing mental disorders.

Of the 121 individuals studied, 85 had a GRIN2A variant and 23 of them developed a mental illness. These results show that carriers of the mutation have a significantly higher risk than those without variations. Furthermore, the patients exhibited strictly psychiatric symptoms, which largely rules out environmental or contextual explanations.

The finding contradicts the general consensus on the polygenic origin of mental disorders. Until now, clinicians have considered that these diseases arise from the interaction of multiple factors, including genetic ones. This study demonstrates for the first time that a mutation in a single gene can decisively influence the development of a mental disorder.

The report also cites previous research that treated NMDA receptor deficiency, caused by the GRIN2A mutation, with L-serine, an amino acid. The four schizophrenia patients who participated in the trial showed remarkable improvements: disappearance of hallucinations, remission of paranoia symptoms, and improved behavior after receiving the treatment.

As this trial was conducted prior to the main study, the authors clarify that it cannot yet be considered a definitive therapeutic method. However, they point out that the efficacy of L-serine can be confirmed in a randomized, prospective, double-blind clinical trial.

Schizophrenia Remains a Huge Enigma

Schizophrenia is a mental illness that manifests itself with delusions, hallucinations, disorganized thinking and language, behavioral changes, and loss of motivation or pleasure. According to the World Health Organization (WHO), this disorder affects some 23 million people worldwide, equivalent to 0.29 percent of the global population. In adults, the rate rises to 0.43 percent, meaning that 1 in every 233 people develops it.

Specialists now have a good understanding of its symptoms and have identified the age ranges in which it typically appears. Effective therapies exist, and several risk factors are recognized, including genetics, neurochemistry, and external elements such as stress or drug use.

Even so, science has not identified a single cause or fully explained the variability among those at risk. Some people develop the illness and others do not, even if both parents have been diagnosed with schizophrenia. There is also no clear strategy for preventing its onset.

This story first appeared in WIRED en Español and has been translated from Spanish.