Rare non-hereditary genetic mutations that occur during early embryo development have been found to increase the risk of developing schizophrenia in the unborn child, according to a study published in Cell Genomics. This discovery could have significant implications for the development of new pharmacological treatments for patients suffering from this psychiatric disorder.
Schizophrenia is a major psychiatric disorder that typically occurs in early adulthood and affects approximately one in 300 people. It is characterized by symptoms such as delusions, hallucinations, social withdrawal, and a progressive deterioration in the ability to make decisions and establish relationships. The causes of schizophrenia are still uncertain, but it is believed to have both genetic and environmental components. Environmental factors such as trauma at birth or in childhood, viral infections, and the use of psychoactive substances may also play a role in predisposing individuals to this condition.
Previous studies had identified around a dozen hereditary mutations associated with the risk of schizophrenia. However, the recent study conducted by Christopher Walsh and colleagues at Boston Children’s Hospital in Massachusetts has discovered two additional mutations that are not hereditary but acquired randomly during early embryonic development.
By analyzing genetic data from over 12,800 adults with schizophrenia and more than 11,600 without, the researchers identified a gene called NRXN1 that was deleted in six individuals with schizophrenia, but none of those without the disorder. This mutation was not hereditary as it was only present in a percentage of blood cells between 14 and 43%, indicating that it occurred in a cell during the early stages of embryo development and was transmitted only to the descendants of that cell.
The NRXN1 gene codes for a protein that regulates the number and density of connections between neurons and is crucial for learning. The researchers believe that mutations like the one found in the blood likely affect other cells in the body, including those in the brain where schizophrenia develops.
In addition to the NRXN1 mutation, the study also found mutations in a gene called ABCB11 in 18 to 27 percent of the blood cells of six participants with schizophrenia who did not respond to a drug treatment for the disease. The ABCB11 gene codes for a protein that carries digestive salts to the liver and is active in neurons that produce dopamine, the neurotransmitter associated with pleasure and reward. Since most drugs used for schizophrenia target these dopamine-producing neurons, the mutation could make the drugs less effective and contribute to drug resistance in some patients.
The researchers believe that these two mutations could play a significant role in the genetic architecture of schizophrenia, and understanding the biological mechanisms behind the disease will help refine pharmacological treatments. Further research is needed to explore the implications of these findings and develop targeted therapies for individuals with schizophrenia.