A research team from the University of Washington, in the United States, has managed to use a technique known as reverse engineering to gather vital information about the disrupted gene network found in patients suffering from schizophrenia. Researchers traced the spontaneous mutations responsible for the brain damage caused by schizophrenia. Their results revealed that patients suffering from schizophrenia may have an improper neurogenesis process from birth, causing the neurons found in the frontal part of he brain to suffer impairments. The study was published at the start of this month in the journal Cell.
Professor Mary-Claire King, a grantee of the NIMH (National Institute of Mental Health), explains that these critical processes can be investigated through the mutations that cause their disruption. Genetic mutations are responsible for the loss of integrity for the whole neurological pathway. She says that the results of their study reveal the mutation of the genes forming a network responsible for the onset of neurogenesis in the prefrontal cortex of the brain, for patients suffering from schizophrenia.
The director of NIMH, Dr Thomas Insel, says that the research team managed to link the genetic mutations to their functional counterparts. This has allowed them to better understand the early development of the brain of patients who will eventually develop signs and symptoms of schizophrenia.
Previous studies have shown that spontaneous mutations are linked to a form of non-familial schizophrenia. These mutations were of genes responsible for the early development process of the brain. However, there was little knowledge about the convergent effects that the genetic mutations had on these pathways. King and her colleagues managed to integrate the genomic data with transcriptome resources available online. For their study, researchers used 105 subjects. They compared the spontaneous mutations that occurred in the genome of the ill subjects with their unaffected siblings.
The results of their investigation revealed that the expression levels of most of the 50 mutated genes had their highest values during fetal development. The expression levels of these genes dropped during childhood. However, in early adulthood, researchers discovered that the expression levels rose again. Their discovery could be linked to the onset of schizophrenia, due to the fact that most patients experience their early symptoms around the same period of young adulthood.
Subjects with an elderly father had an increased chance of suffering from the aforementioned genetic mutations. However, only the affected siblings had a higher chance to suffer from mutations that were responsible for damaging the functions of proteins. These types of mutations were estimated to cause approximately 20% of all schizophrenia cases.
The research team found out that the networks that are formed by these genes vary in connectivity, based on protein interaction and co-expression. The gene networks found in the study subjects were found to have more connection points, when compared to the gene networks of the subjects’ siblings. Researchers found that the mutated genes of patients suffering from schizophrenia formed a much denser network, with more connection points, unlike the gene networks of their siblings, who weren’t affected by schizophrenia.
The results of the current study are also consistent with previous study results that link the prefrontal cortex to the onset of schizophrenia. The prefrontal cortex is the region of the brain responsible for organizing the information collected from the other regions of the brain. It is responsible for the coordination of functions such as planning, self-regulation, memory, attention span, and thinking. The research team suggests that changes in these functions in early adulthood could mean there is a possibility that schizophrenia might set.
The chief of the Genomics Research Branch from the NIMH, professor Thomas Lehner, concludes that the results of the study are very important, revealing that schizophrenia can’t be completely understood unless there is an investigation on the genetic mutations that cause the neurodevelopment impairment responsible for the onset of the disease.