What neuroscientists now know about autism

The following has been produced in partnership with the Lieber Institute for Brain Development, whose mission is to translate genetic knowledge into next generation treatments.

This is one of the reasons why most of us do not remember growing up with so many autistic children today: more and more children have been diagnosed with Spectrum Disorder. autism today. According to the Centers for Disease Control and Prevention, autism now affects 1 in 59 children, compared to 1 in 88 children in 2008 and 1 in 150 children in 2000.

Part of this amazing increase is due to increased awareness of the disease and more accurate diagnoses. Whether there are other factors at play – such as environmental exposures or the fact that parents have babies later in life, research shows that the risks of autism increase – actually still the subject of debate.

"There is not a single autism."

What remains more obscure than prevalence is the underlying biological cause of this disorder. This is partly because autism is actually a constellation of neurological conditions that hinder communication, social skills, motor skills and behavior. "There is not a single autism," says Dr. Daniel Weinberger, director and CEO of the Lieber Institute for Brain Development at Johns Hopkins University. "The term is used to describe many early childhood disorders with many features and manifestations, the main one being the problems of developing social connections." Children usually start showing signs of young children and the majority of children are born with the condition. between them are diagnosed around the age of four.

The genetic plan

Most forms of autism seem to be rooted in genetics or, more specifically, in inherited variations of one or more genes. "In most cases, it's probably caused by the combination of so many genes that influence brain development," says Weinberger. "However, genes do not know anything about social interactions, anxiety or external behavior. They are only responsible for two things: the fixed features, such as the height and color of the hair, and the behavior of the cells. "The DNA in every cell is like a factory foreman," he says, constantly ordering this cell to work.

In other words, when a child inherits a genetic variation, this gene only affects the function of a cell. What is the impact on how an autistic child thinks, acts, and relates to others? This is explained by the understanding that not everyone acts in isolation. As an integral part of the genetics or "genome" of a person, they interact with each other.

"By following the master plan of their genomes, the cells interact and develop mutual relationships as the child develops," explains Weinberger. "They form networks with other cells and grow to become different structures in the brain, such as the hippocampus and the thalamus. While cells process molecular information, the networks to which they belong process cognitive, social, and emotional information. "

Nature against nutrition

Environmental factors such as parent support, nutritious diet, and star school attendance are actually less influential than you think about the behavior of children with autism. According to Weinberger, there is no scientific data showing that a healthy environment will outweigh the effects of a genetic mutation. Despite the lack of scientific evidence, he believes that any human behavior can be modified to some extent. "But the limits, the limits around which parents can make a difference, are very limited," says Weinberger.

"These first five years are a critical time to form the ability to negotiate the most complicated periods of life."

What is very clear, however, is that children exposed to severe stress during their first five years tend to have more social, mental and physical stressors later in life. "Behavior in the face of drugs, diabetes, weight, high blood pressure – the likelihood of all this is increased in people who have experienced extreme stress in their childhood," says Weinberger. "As Freud told us, these first five years are a critical time for the formation of the ability to negotiate the most difficult moments of life."

For a child with autism, this means that even if a loving mother and father, food on the table and a structured family life may not prevail over biology, these factors potentially reduce the risk of developing certain health problems. adulthood.

The treatment of Pitt-Hopkins

Since autism spectrum disorders are so widespread, the Lieber Institute for Brain Development hopes to make progress in helping affected children by first relying on a very distinct type of autism: Pitt's syndrome. -Hopkins. In the United States, although it is only a few thousand children, this rare syndrome may reveal secrets to understanding other types of autism. "Pitt-Hopkins is only a small piece of the pie, but we chose to study it because we know exactly what causes it, while in other forms of Autism, we are still in the process of determining the underlying genetic causes, "Weinberger explains. This syndrome is caused by a single genetic mutation that prevents the TCF4 gene from making a protein important for cell function. As a result, cells that depend on this protein function abnormally.

"As it is a very discrete mutation found on a gene, we can create in the laboratory patterns of Pitt-Hopkins symptoms that reflect the exact cause," Weinberger said. These models allow scientists at the Lieber Institute to examine exactly how genetic mutation is involved in brain development to determine if they can mitigate some of the damage.

"We want to know what's wrong and try to fix it," says Weinberger. "Many people think that you can correct the gene, but it is very difficult and risky. We have adopted a different strategy: assuming you can not modify the genome, let's try to normalize the brain's behavior from what the genome inflicts on it.

Using these models, Lieber researchers discovered that when these cells were stimulated, they acted very abnormally. "The behavior is disrupted because the cells do not trigger properly," says Weinberger. His team traced the problem to a change in a particular protein that constitutes an ionic sodium channel on the cell membrane. This channel serves as a door that allows salt to enter and exit cells. They believe that this mutated ion channel is partially responsible for behavioral changes in children with Pitt-Hopkins.

With this knowledge, the team looked for a drug that could block the ion channel change to determine if the cells were affected. "We have discovered that by targeting the ion channel with a drug, we are restoring cell function," explains Weinberger. "We are probably in a year before seeing the drug tested in humans, but it will be the first potential treatment for autism based on the understanding of a specific cellular mechanism that leads to the syndrome. Pitt Hopkins, a rare form of autism. "

Weinberger insists that this drug will not cure Pitt-Hopkins syndrome, as the mutation probably does not concern only the ion channel. However, he thinks that children who take this drug will be better off because the neurons in their brains will work more normally.

While the work of the Lieber Institute focuses on this form of autism, it is hopeful not only for the children of Pitt-Hopkins and their families. A better understanding of this type of autism opens the way to similar advances for other types of Autism Spectrum Disorders in the future.