Autism may not be confined to the brain

by Rowan Hooper

Special To The Japan Times

Thirteen-year-old Naoki Higashida describes his own personal feelings about having autism as follows:

“I feel a deep envy of people who can know what their own minds are saying, and who have the power to act accordingly. My brain is always sending me off on little missions, whether or not I want to do them. And if I don’t obey, then I have to fight a feeling of horror. Really, it’s like I’m being pushed over the brink into a kind of hell. For people with autism, living itself is a battle.”

Naoki’s book, “The Reason I Jump,” was published in Japanese in 2007. The book, a memoir and personal insight into what life is like with autism, came to international attention when it was published in English in 2013, having been translated by Keiko Yoshida, the wife of English novelist David Mitchell.

The book has been successful, deservedly so, because it offers “neurotypicals” — that is, people not on the autism spectrum — a flavor of what it is like to be on the spectrum. However, it has also changed perceptions of what it means to have autism. If you’ve ever read the book or have personal experience with autism, you may assume that the condition is entirely connected with how the brain is wired. Certainly that was my assumption.

However, a new study suggests that autism may be more complex.

It turns out that some aspects of autism spectrum disorder (ASD) — notably, how the sensation of touch is perceived, how anxiety is generated and certain aspects of social interaction — seem to be linked to defects not in central but in the peripheral nervous system. The peripheral nervous system contains nerves outside of the brain — in our hands and feet, in our limbs, and in all the regions that communicate sensory data to the brain.

The new work has been done at Harvard Medical School, using a mouse model for autism. This method is used to study diseases and disorders that have genetic elements. A mouse strain is made with gene mutations known to be associated with ASD in people, and researchers then study the effects of the genes.

“Advances in mouse genetics have made it possible for us to study genes linked to ASD by altering them only in certain types of nerve cells and studying the effects,” says David Ginty, a professor of neurobiology at Harvard Medical School.

Autism is a complex condition and the causes are not completely understood. There are several genes that have been linked to ASD, however, including one called “Mecp2,” and another called “Gabrb3.”

These, as well as a couple more the study looked at, are important for the normal function of nerve cells. The scientists knew from previous work that mutations in these genes prevent neurons from properly communicating with each other.

“Although we know about several genes associated with ASD, a challenge and a major goal has been to find where in the nervous system the problems occur,” Ginty says. “By engineering mice that have these mutations only in their peripheral sensory neurons, which detect light touch stimuli acting on the skin, we’ve shown that mutations there are both necessary and sufficient for creating mice with an abnormal hypersensitivity to touch.”

People with autism and their friends and families will be well aware of this. People with ASD often report discomfort with certain textures. Simon Baron-Cohen, an autism researcher at Cambridge University in Britain calls this “sensory hypersensitivity.” For children with autism, their bodies are on constant red alert for irritations, which can be triggered by touch and the feeling of clothes that neurotypicals tolerate without a thought.

Ginty and his colleagues measured how the mice reacted to different stimuli, such as a light puff of air on their backs, and they tested whether the mice could discriminate between objects with different textures. Mice with the gene mutations in only their sensory neurons showed heightened sensitivity to touch and weren’t able to discriminate between textures.

Another thing that is commonly commented on about people with autism is their anxiety with social interactions.

“What we’re anxious about is that we’re causing trouble for the rest of you, or even getting on your nerves,” Naoki says.

The Harvard team examined anxiety in the mice by looking at how much mice avoided being out in the open and how much they interacted with mice they’d never seen before. An unexpected result was that the mice with the gene mutations only in peripheral neurons were more anxious and interacted less with other mice. Of course, all these results come with the not inconsiderable caveat that they apply to mice.

“How closely these behaviors mimic anxiety seen in ASD in humans is up for debate,” says Ginty, “but in our field, these are well-established measures of what we consider to be anxiety-like behavior and social interaction deficits.”

One way of thinking about what is causing this behavior in the mice is that they have a problem with the “volume control” in their peripheral sensory neurons. What this means, says Lauren Orefice, a colleague of Ginty’s, is that the volume is turned up all the way in these neurons, leading the animals to feel touch at an exaggerated, heightened level.

Again, this will be familiar to parents of children with autism, who are often extremely sensitive to noise.

“We think it works the same way in humans with ASD,” Ginty says. If they are right, they could look for ways to turn the volume switch back down to normal levels, perhaps through drugs.

Naoki is now 23 and the author of more than 20 books of poetry, fiction and nonfiction. It seems fitting to close this month’s column with another extract from his memoir:

“Criticizing people, winding them up, making idiots of them or fooling them doesn’t make people with autism laugh. What makes us smile from the inside is seeing something beautiful or a memory that makes us laugh.”

Rowan Hooper is the news editor of New Scientist magazine. The second volume of Natural Selections columns translated into Japanese is published by Shinchosha. The title is “Hito wa Ima mo Shinka Shiteru” (“The Evolving Human”). Follow Rowan on Twitter @rowhoop.