By Andy Mitchell
A recent study by researchers led by the University of Iowa’s director of the Iowa Neuroscience Institute, Ted Abel, takes a step forward in research on why autism predominately affects males.
The researchers tested lab mice, studying them for abnormalities in specifically reward-learning behavior. In the test, an action was rewarded with a chocolate drink. This type of learning is mediated by a part of the brain called the striatum and is disrupted in people with autism and other neurodevelopmental disorders.
Nearly one in every 200 cases of autism is caused by the deletion of a section of DNA on a particular chromosome. This type of disorder is also known as a copy-number variation. The mouse model of autism used by the research team is missing the same stretch of DNA.
“One thing you can’t find out by just studying males is seeing how vulnerable they are to disorders in comparison with females with a higher rate of mood disorders like depression and anxiety,” said Nicola Grissom, the first author of the study and an assistant professor of psychology at the University of Minnesota. “Neurodevelopment disorders are more common in boys, while females suffer with a higher rate of mood disorders like depression and anxiety.”
The study found only male mice with the genetic deletion associated with autism have abnormal reward-learning behavior, while the female mice with the same genetic deletion were not affected. In addition, the study found that the sex-specific behavioral differences are accompanied by sex differences in molecular signaling pathways in the striatum brain region.
One of the genes contained in the missing section of DNA is an important signaling protein called ERK1. Activity of this protein affects the function of the striatum — the part of the brain that is involved in reward learning and motivation.
“Somehow, the female brain is able to stabilize the making of a protein called ERK1 that the male is not able to stabilize,” Grissom said. “What I’m working on is trying to find inherent sex differences in decision-making that might explain why the female brain is a little more resilient.”
Abel said the next step is to dissect the neural circuits responsible for this behavior.
“The circuitry we study in these animals can help explain autism,” he said.
“Neurodevelopmental disorders are highly sex-biased: for every girl, three to four boys are affected, e.g., in autism or [ADHD],” said UI psychiatry Professor Thomas Nickl-Jockschat, who was also involved in the research, in an email to The Daily Iowan. “Identifying the molecular mechanism that increases the risk for males is a first step to develop tailored therapeutic strategies that might help to protect males at risk or that even might be the key to develop new therapeutic approaches.”
Abel said as autism therapy is largely reward-based, that method may have to be reconsidered and work on building habits. He also thanked the Simon Foundation for its support in the study and said the study opened up a new avenue in the investigation.