A new discovery has changed the way scientists think about non-inherited schizophrenia.
Rather than individual gene mutations being responsible for schizophrenia on their own, it’s more likely that a gene mutation can damage an entire neural pathway, which creates a ripple effect across networks as the brain develops, according to researchers at the University of Washington.
In fact, what is now known as one disease (schizophrenia) may actually be many different diseases.
“Processes critical for the brain’s development can be revealed by the mutations that disrupt them,” said Mary-Claire King, Ph.D., a UW grantee working on the project. “Mutations can lead to loss of integrity of a whole pathway, not just of a single gene.”
The new research supports the current — and relatively new — model of schizophrenia as a neurodevelopmental disorder in which psychosis is a late, potentially preventable stage of the illness.
In the study, researchers were able to trace back spontaneous gene mutations to where and when they likely caused brain damage.
They found that some individuals might develop the precursors for schizophrenia even before birth, because their brains produced damaged neurons as a developing fetus.
Previous research had already found a connection between gene mutations and non-inherited schizophrenia that could be traced to genes involved in brain development. Until now, however, scientists knew little about how those gene mutations interact and affect pathways in the brain.
For the study, researchers chose to focus on these pathways using an online tool called the transcriptome — an atlas of human brain development that shows where in the brain and when in development genes turn on.
“This approach gives us additional insight into how early development differs in the brain of someone who will eventually manifest the symptoms of psychosis,” said Dr. Thomas Insel, director of the National Institute of Mental Health, which funded the research.
The transcriptome allowed King and her team to analyze the spontaneous gene mutations in people with schizophrenia with no family history of the disease. They then were able to make comparisons with the genes of their unaffected siblings.
As the scientists studied networks of mutated genes that they suspected were linked to schizophrenia, they found that those networks of mutation essentially “turned on” certain schizophrenia-related genes in fetal development. That effect tapered off in childhood, only to increase again in early adulthood — the age when schizophrenia symptoms typically develop.
The new research also supports earlier studies that had implicated the prefrontal cortex in schizophrenia. The prefrontal cortex pulls information from other brain regions to coordinate functions such as thinking, planning, attention span, memory and problem-solving. Problems with these functions are early signs of the illness.