Gastrointestinal Problems Common in Autism Linked to Gene Mutation that Affects Behavior
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This editorial also appeared in the Spring 2016 issue of ARI's Autism Research Review International newsletter.

A new study suggests that the gastrointestinal problems common in autism may stem from gene mutations that are also linked to the behavioral symptoms of the condition.

Kara Gross Margolis and colleagues studied mice carrying a mutation also seen in some individuals with autism. The mutation reduces the activity of the neurotransmitter serotonin by increasing the activity of the serotonin reuptake transporter (SERT), which ferries serotonin back into neurons after it is released.

While serotonin transmits signals in the brain, the brain contains only five percent of the body’s serotonin. Most of the remainder is active in the GI system, and the researchers note that gene mutations that affect serotonin activity will affect the gut as well as the brain.

Previously, the researchers found that mice with the SERT mutation exhibited behaviors very similar to those seen in children with autism—for instance, repetitive behaviors, avoidance of contact with other mice, and reduced vocalizations. In the new study, they found that mice with the mutation have fewer gut neurons, a badly maintained gut lining, and slow gut activity. These changes persisted throughout the mice’s lives.

“Basically,” study coauthor Michael Gershon says, “the gut goes slower and the mice were constipated, which is a common complaint in kids with autism.”

The researchers also found that GI changes related to the SERT mutation could be prevented during prenatal development if the mothers of the mice received the drug prucalopride, which mimics the ability of serotonin to stimulate nerve cell development.

Study coauthor Kara Gross Margolis says, “We see that we can prevent gastrointestinal changes in mice with the SERT mutation, but we still need to learn if we can reverse these changes once they appear.”

Margolis says that parents and doctors need to be aware that GI problems are common in autism. She notes, “The difficulty is that these kids present in a different way. Often they’re not verbal or they have sensory issues so they can’t pinpoint where the pain is coming from. So it’s important that when these patients present with distress or behavioral problems, a gastrointestinal source is considered.”

The researchers conducted a separate experiment to see how increasing serotonin levels in the mice before birth would affect their development. When they did this by giving the mothers of the mice Prozac during pregnancy or knocking out the SERT gene, they found that the offspring had too many neurons, a gut that moved too fast, and a gut lining that was too thick. The researchers say that while they are not recommending that pregnant women stop taking SSRIs, these women need to be aware of their potential effects.

“Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function,” Kara Gross Margolis, Zhishan Li, Korey Stevanovic, Virginia Saurman, Narek Israelyan, George M. Anderson, Isaac Snyder, Jeremy VeenstraVanderWeele, Randy D. Blakely, and Michael D. Gershon, Journal of Clinical Investigation, April 25, 2016 (online). Address: Kara Gross Margolis, Morgan Stanley Children’s Hospital, Columbia University College of Physicians and Surgeons, Department of Pediatrics, Division of Pediatric Gastroenterology, 620 West 168th Street, New York, New York 10032, [email protected]

“GI problems in autism may originate in genes, study suggests,” news release, Columbia University Medical Center, April 25, 2016.