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UW research shows brain bio-markers help detect signs of Autism in infancy

SEATTLE – By using magnetic resonance imaging (MRI) to study the brains of infants who have older siblings with autism, scientists were able to correctly identify 80 percent of the babies who would be subsequently diagnosed with autism at  two years of age.

Researchers from the University of Washington were part of a North American effort led by the University of North Carolina to use MRI to measure the brains of “low-risk” infants, with no family history of autism, and “high-risk” infants who had at least one autistic older sibling. A computer algorithm was then used to predict autism before clinically diagnosable behaviors set in. The study was published Feb. 15 in the journal Nature.

Deanna Fisher, a mother of four who has a four year in therapy at the University of Washington Autism Center put her son, Colin, in the sibling study after her older son was diagnosed with autism.

“We had one kid who had just been diagnosed on the spectrum, let’s monitor our second and see what happens,” said Fisher.

Infants with an older sibling who have autism are at a much high risk of developing the disorder.

These high-risk infants were the focus of a UW study looking at bio-markers that can identify signs of autism as early as possible.

The UW research team of doctors let by Stephen Dager, Annette Estes and Tanya St. John collaborated with universities across North America over a 10 year period studying these high risk infants. Their findings were recently published in the journal "Nature" showing structural differences in the brains of children as young as six months old who went on to develop autism.

"So certain parts of the brain was expanded," said Annette Estes, PhD, and the director of the University of Washington Autism Center.

It's known kids with autism have larger brains but what surprised scientists were that those enlargements in specific parts, called cortical surface area, started showing up in MRI scans in infancy. Those bio-markers can be used as a tool along with monitoring behaviors and developmental milestones.

"Actually predict who goes onto to develop autism in over 80-percent of cases. So these are really powerful markers," said Estes.

Having one child diagnosed with autism, the Fisher's knew they were a high-risk family and put Colin in the study when he was three months old.

"Because he started the study at three months, they flagged him at a year old. It was extremely early, our oldest wasn't diagnosed until shortly before his 5th birthday," said Fisher.

Flagging a child with autism is infancy can be monumental in getting early intervention that makes the difference in child development.

"It was huge for us, in terms of time to adjust and get therapy," said Fisher.

Deirdra Miller, mother of six, whose five children participated in the UW study, were also curious to see if there were red flags in their younger children after their second oldest was diagnosed with autism when he turned four.

"We live in a chaotic house, we have a lot of kids," said Miller.

Nine year old, Newt is on the spectrum.

"He was considered severe when he got his first classic autism diagnosis at four," said Miller. "I know we do our retirement planning in a world where Newt is there with us `til the end of our days," added Miller.

After Newt's diagnosis, the Miller's knew they wanted more kids.

"We`d love them either way, and the level of functioning might not be as bad as Newt. It felt like it was worth the risk, and it was, none of our other children have been diagnosed," said Miller.

All of Newt's younger siblings took part in the UW study, though none have been diagnosed, all had some form of therapy which is also a likely occurrence when an older sibling has autism.

"What these infant sibling studies have shown us is that if you have an older sibling you have about a 1 in 5 chance that the younger baby will end up with autism and then an additional 20-30 percent of these younger siblings will have other related challenges like anxiety or specific language impairments," said Estes.

Miller says because all of the children have had some form of therapy, they have a better appreciation for Newt's shortcomings.

"It's another similarity they have with their brother, they can kind of appreciate what he goes through," said Miller. She quit her job as a dula to take care of Newt, his needs and decided to home school all six children.

"Typically, the earliest we can reliably diagnose autism in a child is age 2, when there are consistent behavioral symptoms, and due to health access disparities the average age of diagnosis in the U.S. is actually age 4," said Estes. "But in our study, brain imaging biomarkers at 6 and 12 months were able to identify babies who would be later diagnosed with Autism Spectrum Disorder (ASD)," she added.

The predictive power of the team's findings may inform the development of a diagnostic tool for ASD that could be used in the first year of life, before behavioral symptoms have emerged.

"We don't have such a tool yet," said Estes. "But if we did, parents of high-risk infants wouldn't need to wait for a diagnosis of ASD at 2, 3 or even 4 years and researchers could start developing interventions to prevent these children from falling behind in social and communication skills."

People with ASD — which includes three million people in the United States — have characteristic social communication deficits and demonstrate a range of ritualistic, repetitive and stereotyped behaviors.

This research project included hundreds of children from across the country and was led by researchers at four clinical sites across the United States: the University of North Carolina-Chapel Hill, UW, Washington University in St. Louis and The Children's Hospital of Philadelphia. Other key collaborators are at the Montreal Neurological Institute, the University of Alberta and New York University.

"We have wonderful, dedicated families involved in this study," said Stephen Dager, a UW professor of radiology, and associate director of the UW Autism Center, who led the study at the UW. "They have been willing to travel long distances to our research site and then stay up until late at night so we can collect brain imaging data on their sleeping children. The families also return for follow-up visits so we can measure how their child's brain grows over time. We could not have made these discoveries without their wholehearted participation," said Dager.

Researchers obtained MRI scans of children while they were sleeping at 6, 12 and 24 months of age. The study also assessed behavior and intellectual ability at each visit, using criteria developed by Estes and her team. They found that the babies who developed autism experienced a hyper-expansion of brain surface area from 6 to 12 months, as compared to babies who had an older sibling with autism but did not themselves show evidence of autism at 24 months of age. Increased surface area growth rate in the first year of life was linked to increased growth rate of brain volume in the second year of life. Brain overgrowth was tied to the emergence of autistic social deficits in the second year.

The researchers input these data — MRI calculations of brain volume, surface area, and cortical thickness at 6 and 12 months of age, as well as sex of the infants — into a computer program, asking it to classify babies most likely to meet ASD criteria at 24 months of age. The program developed the best algorithm to accomplish this, and the researchers applied the algorithm to a separate set of study participants.

Researchers found that, among infants with an older ASD sibling, the brain differences at 6 and 12 months of age successfully identified 80 percent of those infants who would be clinically diagnosed with autism at 24 months of age.

If these findings could form the basis for a "pre-symptomatic" diagnosis of ASD, health care professionals could intervene even earlier.

"By the time ASD is diagnosed at 2 to 4 years, often children have already fallen behind their peers in terms of social skills, communication and language," said Estes, who directs behavioral evaluations for the network. "Once you've missed those developmental milestones, catching up is a struggle for many and nearly impossible for some."

Research could then begin to examine interventions on children during a period before the syndrome is present and when the brain is most malleable.  Such interventions may have a greater chance of improving outcomes than treatments started after diagnosis.

"Our hope is that early intervention, before age two, can change the clinical course of those children whose brain development has gone awry and help them acquire skills that they would otherwise struggle to achieve," said Dager.

The research team has gathered additional behavioral and brain imaging data on these infants and children — such as changes in blood flow in the brain and the movement of water along white matter networks — to understand how brain connectivity and neural activity may differ between high-risk children who do and don't develop autism.

"These longitudinal imaging studies, which follow the same infants  as they grow older, are really starting to hone in on critical brain developmental processes that can distinguish children who go on to develop ASD and those who do not," said Dager. "We hope these ongoing efforts will lead to additional biomarkers, which could provide the basis for early, pre-symptomatic diagnosis and serve also to guide individualized interventions to help these kids from falling behind their peers."