Courchesne and his team used frozen brain tissue from the prefrontal cortex of autistic children, aged two to four, and control children who are not autistic, who had passed away to analyze brain tissue gene expression. The prefrontal cortex is the part of the brain responsible for cognitive communication and social development, and its development is abnormal in autistic children. They found that a large number of genes that control the number of brain cells were expressed incorrectly.
Many studies have shown that brain cells in autistic individuals may be too small and undeveloped. After cells are born, they differentiate into specific types of brain cells that are in charge of the different types of information processing. The abnormalities in these cells occur in the second and third trimester of pregnancy, the time span during which most brain cells are created.
“This evidence indicates that biological abnormalities in autism began in the prenatal stage and that the biological abnormalities of autism are complex,” Courchesne said. “They involve a number of large networks or systems in genes and then the regulation of those systems with too much or too little gene activity in those genes is responsible.”
They found evidence that many of the abnormally expressed genes correctly copied DNA during cell divisions. This suggests that the DNA defects associated with autism may not be detected while cells are dividing during prenatal cell development.
“Those DNA defects may creep into new cells that are being generated during prenatal development,” Courchesne said. “Those DNA defects may alter the functional integrity of brain cells.”
The first set of genes that were functionally abnormal was the sets of genes that regulate the number of brain cells. Courchesne said this may explain why many people with autism have an excess number of brain cells in the prefrontal area, and why the abnormal activity involved in DNA checking and correction may explain why some brain cells do not function correctly.
The team then found abnormal activity of genes in the blocks of frontal tissue that regulate the organizational patterning of the brain. They found abnormal activity in the genes that regulate the further development of cells. Courchesne said they think this could explain why autism affects cognitive functions.
About a decade ago, it was discovered that at young ages, the majority of autistic individuals have a brain that is too big. As the child develops and matures, there appears to be a loss of brain tissue. Courchesne and his team found evidence that there may be a growing loss of neurons in autistic individuals. The normal spacing of neurons begins to become more irregular, suggesting irregular locations of loss due to loss of brain tissue.
The team then looked at adults with autism and found different signatures of gene activity that point to loss of cells and remodeling of brain conditions.
“What we don’t know is whether those changes are improving connections or removing maladaptation connections, we just don’t know,” Courchesne said. “But we do know there’s a different profile that suggests some kind of remodeling. And whether it’s ultimately beneficial or not remains for future studies to figure out.”
Another part of their study discovered evidence that would explain why autism is genetically different in every individual with autism. There was overlap within the network in the brain to other individuals with autism, but it was incomplete. Each person has his own set of genes within a network that were the most effective. Then another person has a somewhat overlapping, but different set of genes within the same network.
These genetic networks with abnormalities are the cause of autism. It can be confusing to understand the genes involved in autism because each person with autism has a different set of genes within the same network.
“That’s probably why it’s so hard to understand what’s been so hard to get at the genetic root basis of autism,” Courchesne said.
