Study Picks up Autism Broadcast in Tiny Antennae on Cells


Jessica Wright

Mutations in a section of chromosome 16 that is linked to autism have an unexpected effect: They alter the miniscule, static hairs, called cilia, that adorn the surface of all cells. The findings, reported 7 May in the American Journal of Human Genetics, suggest that problems with these cilia may contribute to autism1.

“We don’t know what the ciliary contribution to autism is, but there is one. There's no question about it,” says Nicholas Katsanis, professor of cell biology at Duke University in Durham, North Carolina, and one of the researchers on the study.

People with too few or too many copies of a segment of chromosome 16 called 16p11.2 show a wide range of features. Those with deletions, for example, tend to have unusually large heads and obesity. Those with duplications typically have small heads and minimal body fat. Roughly 20 percent of people with either variant have autism.

The new study suggests that some of these symptoms stem from abnormal cilia. It also raises the possibility that drugs that target these cilia ease symptoms of autism. For example, the researchers found that a mutation in CEP290, a gene necessary for the formation of cilia, mitigates the consequences of a mutation in a 16p11.2 gene. A drug could try to mimic that effect.

They also found a girl with a 16p11.2 deletion and a CEP290 mutation who has milder symptoms than many other people with the deletion.

“The possible role of ciliary genes [in autism] is intriguing,” says Raphael Bernier, associate professor of psychiatry at the University of Washington in Seattle, who was not involved in the study.

Super hairs:

In the new study, Alexandre Reymond and his colleagues analyzed gene expression in the blood of 50 people with deletions and 31 people with duplications in 16p11.2. They found 1,188 genes whose expression is altered in these people relative to 17 controls.

Among the genes is a group known for its role in Bardet-Biedl and Joubert syndromes, disorders caused by mutations in ciliary genes. Bardet-Biedl syndrome leads to kidney problems, vision loss, obesity and some autism-like traits, such social deficits and restricted behaviors2. Joubert syndrome has also been linked to autism.

Still, no one had followed up on how mutations in cilia genes might lead to autism symptoms.

Of the 30 genes that have been linked to Bardet-Biedl and Joubert syndromes, 10 turned up in Reymond’s analysis.

“This of course raised our eyebrows,” says Reymond, associate professor at the University of Lausanne in France.

Reymond then remembered that his colleague Katsanis had studied cilia early in his career. But Katsanis had switched fields to autism because, he says, he was tired of working on cilia.

“Alex calls me on my cell [phone] and says, ‘Guess what? We think that there's a link between the 16p pathology and cilia,’” Katsanis recalls. “I think what I said to him was, ‘Bullshit,’ and ‘Oh, good Lord, no!’”

To see how 16p11.2 genes might affect cilia on neurons, Katsanis and Reymond turned to mice. Mice with deletions of the region show abnormal expression of cilia genes: higher expression of CEP290, for example, and lower expression of another gene, BBS7. The cilia’s shape is not obviously abnormal, however.

The duplication has the opposite effect on these two genes. And the mice have abnormally short cilia in a part of the hippocampus, a brain region involved in memory.

The researchers also manipulated cilia genes in zebrafish embryos with 16p11.2 mutations. Blocking the expression of KCDT13, a gene in the 16p11.2 region, results in fish with enlarged heads, reminiscent of the increased head size seen in people with 16p11.2 deletions, Katsanis and his team reported in 2012. But when the researchers blocked the expression of CEP290 or raised that of BBS7 in these zebrafish, the fish’s heads were smaller, closer in size to those of normal fish.

“It’s intriguing that the ciliary genes actually rescue the phenotype,” says Lilia Iakoucheva, assistant professor of psychiatry at the University of California, San Diego, who was not involved in the study.

Some of these genes may turn out to modify the effects of autism-linked mutations, says Reymond. For example, the researchers looked at more than 300 families with a history of 16p11.2 mutations and found one particularly intriguing case.

The girl they identified has a 16p11.2 deletion and a mutation in CEP290. She does not have seizures or autism and has a normal head size. Her intelligence quotient is 89 — lower than that of her parents but higher than average for people with the deletion.

Her case suggests that similar mutations offset the effects of 16p11.2 mutations, says Reymond. “It’s an N of one, but at least the N of one doesn’t go against our hypothesis,” he says.

News and Opinion articles on are editorially independent of the Simons Foundation.


1. Migliavacca E. et al. Am. J. Hum. Genet. 96, 784-796 (2015) PubMed

2. Kerr E.N. et al. Clin. Genet. Eput ahead of print (2015) PubMed


What If People with Autism Are Actually Hyperfunctional?

Source: TIME

Most people who think about autism think of people who struggle or are inept in some ways, especially when it comes to social behaviors. But there’s growing evidence that the autistic brain may actually be more super-wired to detect and absorb cues from the outside world.

Now, a new study published in the journal Frontiers in Neurosciencesuggests that the brains of people with autism are actually hyperfunctional rather than stunted or impaired, and that if treated early in a very predictable environment, symptoms could diminish.

In 2007, researchers Kamila Markram, Henry Markram, and Tania Rinaldi developed an alternative theory for what autism is, called the “Intense World Syndrome.” They believe that autism is not some form of mental deficit, but that the brain is actually supercharged and hyperfunctional. This makes stimuli overwhelming to people with autism, causing them to socially and emotionally withdraw as a mode of self-protection.

In the new study, researchers at the Swiss Federal Institute of Technology in Lausanne (EPFL), including Henry Markram and Kamila Markram, showed how autism might be treated following this theory.

The researchers took a group of rats and exposed them to a drug called valproate (VPA), which is a process commonly used to model autism in the rodents. The researchers then exposed the rats to three different environments. The first was a standard environment: a typical laboratory cage. The second was a unpredictable enriched environment, which had things like a running wheel, toys and places to hide. In this environment, the researchers would regularly clean the cages, change out the toys and reorganize the space. The third was a predictable enriched environment, which had stimuli like toys and a running wheel, but after every cleaning the cage remained the same and nothing was moved out of place.

The researchers found that rats exposed to VPA were more sensitive to their living environments compared to control rats. The VPA-exposed rats living in the predictable environment did not develop the same emotional behaviors like anxiety and fear that the VPA-exposed mice living in the unpredictable environment or the standard environment did. The researchers concluded that an unpredictable or impoverished environment exacerbates the autism-like symptoms in rats, but a very predictable environment can prevent these symptoms from developing.

Though the study is still preliminary and was done in rats and not humans, Kamila Markram says she thinks it does have implications for how children with autism might be treated in the future. “Many therapies do recognize that structure and predictability is important, but none of the approaches has put this at the center,” she says. “We say you have to put it at the center and you need to be addressing sensory overflow.”

In the ideal scenario, Markram says kids with autism could be diagnosed when they are very young and then raised in a very stable and predictable environment. “You would approach the child from the same direction, books are on the same shelf, toys are always in the same place,” she says.

Markam says that it’s also necessary to change the way people view the disorder as a whole. “It’s important to us that we move away from the autism as a deficit model. These children are hyperfunctional and they can’t bear their environment,” says Markan. “If you have that view, it changes the way you look at research. If you’re a parent, you’ll treat your child in a different way.”


Air Pollution Exposure May Be Linked to a Child's Risk of Autism, a Recent Study Suggests.

Source: NewsMax

The controversial findings echo similar results from a study last winter that found an increased risk of autism among children of women exposed to more smog late in pregnancy.

This new study -- which does not establish a direct connection between dirty air and autism -- did not find a statistically significant increased risk for autism related to air pollution exposure at any specific time during pregnancy.

Instead, the authors found a child's odds of autism were 1.5 times greater when air pollution exposure was greater across the entire span of time from pre-pregnancy until the child was 2 years old.

"These findings are striking because they suggest that cumulative exposures over the course of the pregnancy may be important, as opposed to any individual period during the pregnancy," said study author Evelyn Talbott, a professor of epidemiology at the University of Pittsburgh. But more research would be necessary to understand how pollution might affect autism risk, she said.

Autism spectrum disorder -- a group of developmental disabilities that can cause significant communication and social challenges -- affects 1 in 68 children in the United States, according to the U.S. Centers for Disease Control and Prevention.

The research involved 443 children living in six counties in southwestern Pennsylvania, about half of whom had autism. Researchers compared air pollution exposure -- based on all addresses where the mothers reported living -- before and during their mothers' pregnancy and in the children's first two years of life.

The researchers adjusted their calculations to account for each mother's age, education and race, and whether she smoked.

The type of pollution measured was fine-particle air pollution, included in smog. It's composed of small particles from car exhaust or other forms of burning wood, coal and other fossil fuels that can be inhaled deep into the lungs, according to the U.S. Environmental Protection Agency. The American Lung Association ranks southwestern Pennsylvania among the nation's worst regions for this type of pollution.

The children's odds of having autism were 45 percent greater if they were exposed to the highest levels at age 2, the study found. Their odds were 51 percent greater if the highest exposure occurred from three months before pregnancy through the child's second year.

The findings were published in the July issue of the journal Environmental Research.

It is not clear, however, how significant the findings are overall, since the study cannot show cause and effect between air pollution and autism, said Dr. Alyson Gutman, an attending physician in developmental and behavioral pediatrics at Cohen Children's Medical Center in New Hyde Park, N.Y.

"We know that there are several interacting factors that likely contribute to the cause of autism spectrum disorders," Gutman said. Those factors include genetics, environmental risk factors and medical risk factors, such as a history of prematurity, she said.

"Exposure to pollutants may be a contributing factor," she said. "However, it is difficult to determine the significance of this risk factor."

Dr. Glen Elliott, chief psychiatrist and medical director of Children's Health Council in Palo Alto, Calif., where he specializes in autism, expressed skepticism about the study's conclusions.

"I am stunned that the editors permitted the authors to make the claims they did," he said. He noted that the only single point in time when the data was statistically significant was when the children were 2 years old.

"The authors offer no theoretical basis for how particulate matter that the mother breathes might affect the child's development," Elliott said. "They also did not add the much-needed caution that correlation does not equal causation, even if their data were much stronger than it is."

If parents are concerned about their possible exposure to air pollution, they should discuss their concerns with their doctors, Gutman said.

People can also check on their local air quality on various websites and purchase air filters that target smaller particles and pollutants within the home, said Talbott.

"They can also write to lawmakers to put pressure on them to make policies that reduce air pollution and harmful emissions," Talbott said. "More work needs to be conducted both in other geographic areas of the United States as well as in other countries to further our understanding of this association."