Staff Writer Jorja Adamczyk discusses recent research suggesting a link between genes and mental illness.
The University of Leipzig in Germany has recently discovered a strong link between a single gene, GRIN2A, and the development of mental illness. This is seen as a significant breakthrough within the scientific community.
Although genetics have long been known to play a role in psychiatric illness, not many genes have ever been so clearly shown to confer such a high risk for isolated mental disorders. This challenges more generally accepted ideas about the influence of polygenic inheritance and gene-environment interaction in mental illness.
The study recognises GRIN2A as one of the few genes associated with a plethora of mental disorders, such as schizophrenia and bipolar disorders. Previously, the only single genes to be considered as a significant factor for schizophrenia development were SETD1A, DISC1 and CACNA1, but only in the context of combined neurodevelopmental disorders rather than isolated psychiatric conditions.
It was found that individuals with GRIN2A null variants have a much higher risk of developing mental disorders than those in the FinnGen consortium, a large-scale, public-private research project that combines genome data with digital health record data.
Although GRIN2A is present in these individuals, the null variant means that it is non-functional. Psychiatric symptoms often begin in childhood or adolescence, which is much earlier than typical psychiatric onset.
The study reports increased hazards in developing various psychiatric disorders; 12 times more in developing mood disorders, six times for anxiety disorders and an especially shocking 87 times more for psychotic disorders.
This study challenges some beliefs that psychiatric disorders are purely polygenic (involving multiple genes), opening the door to precision treatment.
Researchers identified NMDA receptor dysfunction as a key factor in the development of these conditions, which suggests that enhanced NMDA receptor signalling may lead to clinical improvements. This may include a reduction in paranoia, hallucinations and behavioural disruptions.
The discovery of GRIN2A null variants advances the developing field of precision psychiatry, in which treatments are targeted to an individual’s unique genetic makeup, potentially resulting in more effective results with less side effects. However, it is important to note that this single study is just the start, as researchers hope that clinical trials can prove these theories as fact.
“GRIN2A variants are now associated with a wide range of phenotypes, including isolated psychiatric illness. If replicated, these findings may have implications for genetic testing in psychiatry, especially if the benefits of L-serine treatment are formally validated.”
Deb Pal Professor of Epilepsy in the Institute of Psychiatry, Psychology and Neuroscience, who has previously researched GRIN2A, in the context of epilepsy and molecular mutations.
