Nav: Home

Brains of people with autism spectrum disorder share similar molecular abnormalities

December 05, 2016

Autism spectrum disorder is caused by a variety of factors, both genetic and environmental. But a new study led by UCLA scientists provides further evidence that the brains of people with the disorder tend to have the same "signature" of abnormalities at the molecular level.

The scientists analyzed 251 brain tissue samples from nearly 100 deceased people -- 48 who had autism and 49 who didn't. Most of the samples from people with autism showed a distinctive pattern of unusual gene activity.

The findings, published Dec. 5 in Nature, confirm and extend the results of earlier, smaller studies, and provide a clearer picture of what goes awry, at the molecular level, in the brains of people with autism.

"This pattern of unusual gene activity suggests some possible targets for future autism drugs," said Dr. Daniel Geschwind, the paper's senior author and UCLA's Gordon and Virginia MacDonald Distinguished Professor of Human Genetics. "In principle, we can use the abnormal patterns we've found to screen for drugs that reverse them -- and thereby hopefully treat this disorder."

According to the Centers for Disease Control and Prevention, about 1.5 percent of children in the U.S. have autism; the disorder is characterized by impaired social interactions and other cognitive and behavioral problems. In rare cases, the disorder has been tied to specific DNA mutations, maternal infections during pregnancy or exposures to certain chemicals in the womb. But in most cases, the causes are unknown.

In a much-cited study in Nature in 2011, Geschwind and colleagues found that key regions of the brain in people with different kinds of autism had the same broad pattern of abnormal gene activity. More specifically, researchers noticed that the brains of people with autism didn't have the "normal" pattern for which genes are active or inactive that they found in the brains of people without the disorder. What's more, the genes in brains with autism weren't randomly active or inactive in these key regions, but rather had their own consistent patterns from one brain to the next -- even when the causes of the autism appear to be very different.

The discovery suggested that different genetic and environmental triggers of autism disorders mostly lead to disease via the same biological pathways in brain cells.

In the new study, Geschwind and his team analyzed a larger number of brain tissue samples and found the same broad pattern of abnormal gene activity in areas of the brain that are affected by autism.

"Traditionally, few genetic studies of psychiatric diseases have been replicated, so being able to confirm those initial findings in a new set of patients is very important," said Geschwind, who also is a professor of neurology and psychiatry at the David Geffen School of Medicine at UCLA. "It strongly suggests that the pattern we found applies to most people with autism disorders."

The team also looked at other aspects of cell biology, including brain cells' production of molecules called long non-coding RNAs, which can suppress or enhance the activity of many genes at once. Again, the researchers found a distinctive abnormal pattern in the autism disorder samples.

Further studies may determine which abnormalities are drivers of autism, and which are merely the brain's responses to the disease process. But the findings offer some intriguing leads about how the brains of people with autism develop during the first 10 years of their lives. One is that, in people with the disorder, genes that control the formation of synapses -- the ports through which neurons send signals to each other -- are abnormally quiet in key regions of the brain. During the same time frame, genes that promote the activity of microglial cells, the brain's principal immune cells, are abnormally busy.

This could mean that the first decade of life could be a critical time for interventions to prevent autism.

The study also confirmed a previous finding that in the brains of people with autism, the patterns of gene activity in the frontal and temporal lobes are almost the same. In people who don't have autism, the two regions develop distinctly different patterns during childhood. The new study suggests that SOX5, a gene with a known role in early brain development, contributes to the failure of the two regions to diverge in people with autism.
-end-
The study's lead authors are Neelroop Parikshak, Vivek Swarup and Grant Belgard of UCLA; other co-authors are Gokul Ramaswami, Michael Gandal, Christopher Hartl, Virpi Leppa, Luis de la Torre Ubieta, Jerry Huang, Jennifer Lowe and Steve Horvath of UCLA; Manuel Irimia of the Barcelona Institute of Science and Technology; and Benjamin Blencowe of the University of Toronto.

The research was funded in part by the National Institutes of Health.

University of California - Los Angeles

Related Autism Articles:

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.
Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.
Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.
Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.
Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.
Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.
State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.
Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.
Pinpointing the origins of autism
The origins of autism remain mysterious. What areas of the brain are involved, and when do the first signs appear?
Genes, ozone, and autism
Exposure to ozone in the environment puts individuals with high levels of genetic variation at an even higher risk for developing autism than would be expected just by adding the two risk factors together, a new analysis shows.
More Autism News and Autism Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

TED Radio Wow-er
School's out, but many kids–and their parents–are still stuck at home. Let's keep learning together. Special guest Guy Raz joins Manoush for an hour packed with TED science lessons for everyone.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.