They associate schizophrenia with mutations produced in the womb

It is believed that the schizophrenia, a psychiatric disorder that appears in adulthood, is triggered by a combination of environmental and genetic factors, but its exact cause is still unclear. Today, a study relates this disease with mutations in utero.

The research, published Thursday in the journal Cell Genomics, has found a correlation between schizophrenia and somatic copy number variants, a type of mutation that occurs early in development but after the fetus has inherited the copy number. genetic material.

This study is one of the first to rigorously describe the relationship between somatic (not inherited) genetic mutations and the risk of schizophrenia.

“We thought that genetics was the study of heredity but now we know that genetic mechanisms go much further. We are looking at mutations that are not inherited from the parents.”explained lead author Chris Walsh, a Howard Hughes Medical Institute investigator and chief of genetics and genomics at Children’s Hospital Boston.

The researchers analyzed genotyping and marker data from more than 20,000 blood samples from people with and without schizophrenia from the Psychiatric Genomics Consortium.

From there, they identified two genes -NRXN1 and ABCB11- that were correlated with cases of schizophrenia when altered in utero.

NRXN1, a gene that helps transmit signals throughout the brain, has been linked to schizophrenia before, but this is the first study to associate the disease with somatic, non-inherited mutations of NRXN1.

somatic mutations

Unlike heritable mutations, which are present in all cells of the body, somatic mutations are only present in a fraction of cells depending on when and where the mutation occurred.

If a mutation occurs early in development, the variant is expected to be present throughout the organism in a mosaic fashion.

Based on this principle, researchers can identify somatic mutations that occurred early in development and are present not only in the brain, but also in a fraction of blood cells.

“If a mutation occurs after fertilization, when there are only two cells, the mutation will be present in half the cells of the body”Walsh explained.

“If it is produced in one of the first four cells, it will be present in about a quarter of the cells in the body, and so on.”he detailed.

A gene out of nowhere

The second gene the researchers identified, ABCB11, is best known for encoding a liver protein.

“That one came out of nowhere”revealed Eduardo Maury, a student in the Harvard-MIT MD-PhD program.

“There have been some studies associating mutations in this gene with treatment-resistant schizophrenia, but it has not been strongly implicated in schizophrenia per se.”

When the team investigated further, they discovered that ABCB11 is also expressed in very specific subsets of neurons that transport dopamine from the brainstem to the cerebral cortex.

Most schizophrenia drugs are thought to act on these cells to lower an individual’s dopamine levels, so this could explain why the gene is associated with treatment resistance.

The team is currently trying to identify other acquired mutations that might be associated with schizophrenia.

Since the study looked at blood samples, it will be important to examine more specific mutations in the brain that might have been too subtle or recent in a patient’s life for this test to detect.

In addition, somatic duplications could be a poorly investigated risk factor associated with other disorders.

“With this study, we show that it is possible to find somatic variants in a psychiatric disorder that develops in adulthood. This raises questions about what other disorders could be regulated by these types of mutations.” Maury concluded.

Source: EFE