Amazing stuff! This suggests that perhaps more genetics research is necessary for mental disorders!
"In a breakthrough study, scientists have discovered that a variant in one gene, GRIN2A, can directly cause mental illness – something previously believed to be the result of several mutations working together. What's more, these conditions often present in childhood instead of more commonly during adulthood. ..."
"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. ..."
From the abstract:
"Rare genetic factors have been shown to substantially contribute to mental illness, but so far, no precision treatments for mental disorders have been described. It was recently identified that rare variants in GRIN2A encoding the GluN2A subunit of the N-methyl-D-aspartate receptor (NMDAR) confer a substantial risk for schizophrenia.
To determine the prevalence of mental disorders among individuals with GRIN2A-related disorders, we enquired the presence of psychiatric symptoms in 235 individuals with pathogenic variants in GRIN2A who had previously enrolled in our global GRIN registry.
We identified null variants in GRIN2A (GRIN2Anull) to be significantly associated with a broad spectrum of mental disorders including schizophrenia compared to a longitudinal population cohort (FinRegistry) as well as missense variants (GRIN2Amissense).
In our cohort, GRIN2Anull-related mental disorders manifest in early childhood or adolescence, which is substantially earlier than the average adult onset in the general population. In 68% of co-incident epilepsy and mental disorder, mental disorders start after epilepsy offset and the age of epilepsy offset correlated with mental disorder onset.
GRIN2Anull-related phenotypes appear to occasionally even manifest as isolated mental disorder, i.e. as schizophrenia or mood disorder without further GRIN2A-specific symptoms, such as intellectual disability and/or epilepsy.
As L-serine is known to mediate co-agonistic effects on the NMDAR, we applied it to four individuals with GRIN2Anull-related mental disorders, all of whom experienced improvements of their neuropsychiatric phenotype.
GRIN2Anull appears to be the first monogenic cause of early-onset and even isolated mental disorders, such as early-onset schizophrenia.
Genetic testing should be considered in the diagnostic work-up of affected individuals to improve diagnosis and potentially offer personalized treatment as increasing brain concentrations of NMDAR co-agonists appears to be a promising precision treatment approach successfully targeting deficient glutamatergic signaling in individuals with mental disorders, i.e. due to GRIN2Anull."
Changes in a single gene can cause mental illness (original news release)
Fig. 1: Cumulative incidence of mental disorders and Hazard Ratios for index carriers of pathogenic GRIN2A variants carriers.
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