Schizophrenia is thought to affect 1 in 300 people, or about 0.32 percent of the global population, and treatment options are limited because of a poor understanding of the mechanisms underlying the disorder. Researchers have now linked a type of genetic mutation in the developing brain to an increased risk of schizophrenia. Genetic mutations that are inherited from parents are known as germline mutations, but mutations can also in cells arise after birth. These so-called somatic mutations can have a variety of impacts, and this study has revealed some somatic mutations that can affect neurodevelopment and genes related to schizophrenia risk.
This may be the first study to investigate how somatic mutations or variants can increase the risk of schizophrenia, especially in the context of other genetic factors that are inherited. The findings have been reported in Science.
In this work, the researchers analyzed samples of brain tissue that had been obtained post-mortem from schizophrenia patients and unaffected individuals. They focused on a region of the brain known as the dorsolateral prefrontal cortex, which is known to be crucial to cognition The genomes of individual neurons from this area were sequenced to reveal all of the variations in the DNA.
This work revealed that schizophrenia patients had significantly more somatic mutations in neurons of the dorsolateral prefrontal cortex compared to unaffected individuals. The researchers suggested that some of these mutations are affecting biological functions, leading to an increase in the risk of schizophrenia. Some somatic mutations were found in transcription factors, which can affect the expression of many other genes, including genes that are related to neurodevelopment and genes that have been previously linked to schizophrenia.
"This study provides an important insight into the genetic factors contributing to schizophrenia," said co-corresponding study author Andrew Chess, PhD, a Professor of Genetics and Genomic Sciences at Icahn Mount Sinai. "Beyond the inherited mutations we typically think of, we now see that mutations arising during brain development may also contribute to the disease."
Some mutations were also associated with inflammatory signals, which could indicate that environmental influences such as a maternal infection during pregnancy, may be related to the development of the disorder.
The researchers are planning to learn more about the impact of these mutations. This research has highlighted the importance of considering different genetic factors when considering the causes of schizophrenia. While more research will be needed, it may eventually help open up new treatment options for patients.
"As we continue to explore these mutations and their effects on brain function, we hope to uncover new pathways for potential therapeutic interventions," said Chess. "By expanding the number of cases we study and using cutting-edge technologies, we aim to better understand the genetic mechanisms behind schizophrenia and ultimately improve outcomes for those affected by the disorder."
Sources: The Mount Sinai Hospital, Science