Schizophrenia is a chronic mental condition, and so far, doctors had identified it as a condition caused by an inherited genetic mutation. Now, new research published in Cell Genomics on 6 July has found that schizophrenia may not be a genetic condition and could be caused by non-inherited or by mutations that occur during an embryo’s development in the womb. This kind of mutation is called a somatic mutation.
The breakthrough research could potentially help in developing protocols that can screen a foetus for such conditions as well as open up the possibility of new therapies for schizophrenia.
The study by Boston Children’s Hospital, USA shows the occurrence of higher somatic mutation in schizophrenia-affected individuals compared to those without the conditions.
Read more: Voices and visions of schizophrenia
Read more: Affected brain regions in schizophrenia
The genetic offender
Till now, the exact cause of schizophrenia is not entirely understood. Schizophrenia affects a person’s thoughts, feelings, and behaviour, typically emerging in late adolescence or early adulthood. However, it can occur at any age. According to World Health Organisation (WHO) 2022 report, schizophrenia affects approximately 24 million people or 1 in 300 worldwide.
Previous studies suggest that a combination of genetic, environmental, and neurological factors contribute to schizophrenia, with inherited genes being the most significant cause of it. However, other studies have shown the risk for schizophrenia occurs either due to a single change in the DNA (single nucleotide polymorphisms) or multiple numbers of the gene in the DNA (copy number variants).
“We originally thought of genetics as the study of inheritance. But now we know that genetic mechanisms go way beyond that,” says senior author Chris Walsh, an investigator at the Howard Hughes Medical Institute at Boston Children’s Hospital USA, in a statement. He adds that they looked at mutations not inherited from the parents.
Read more: Tackling schizophrenia, the yoga way
What they did
Studies have shown that inherited mutation occurs in all body cells. Whereas somatic mutations are present only in some cells based on when and where a mutation occurs. Researchers can identify the somatic mutation that occurred during early development as changes are present in the brain and a fraction in blood cells. The researchers of the study hypothesised that the risk of schizophrenia is associated with somatic mutation.
The researchers analysed the blood sample of 12,834 schizophrenia-affected individuals and 11,648 healthy individuals from the Psychiatric Genomic Consortium database. They conducted a genomic study to identify somatic mutations in all the individuals. Based on the genomic study, researchers identified changes in two genes, NRXN1 and ABCB11, in body cells. These mutations were found only in the group with schizophrenia, indicating that these changes occur during the early development in the mother’s womb.
Dr Walsh explained that if a mutation occurs after fertilisation when there are only two cells, the mutation will be present in half of the cells of the body [early development of the foetus].
“If it occurs in one of the first four cells, it will be present in about a quarter of the cells of the body, and so on,” he adds.
Dual genes chemistry
Research has found that NRXN1 genes help in transmitting signals throughout the brain. Hence, any change in the gene disrupts synaptic transmission and neuronal communication in the brain. Whereas ABCB 11 is mostly known to have its function in the liver.
However, in this study, researchers observed that ABCB 11 is found in specific neurons that carry dopamine from the brainstem to the cerebral cortex. This result explained the association between this gene and schizophrenia.
“With this study, we show that it is possible to find somatic variants in a psychiatric disorder that develops in adulthood,” says Eduardo Maury, a PhD student at Harvard-MIT, in the statement.
