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Autism 'patchwork' begins during pregnancy: US study

Baby Steps

Wednesday, April 09, 2014    

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WASHINGTON, USA (AFP) — The brains of children with autism contain a built-in patchwork of defects, suggesting that the developmental disorder begins while they are growing in the womb, said a US study.

Researchers described their findings in the New England Journal of Medicine as "direct evidence" of a prenatal origin for autism, which affects as many as one in 88 children in the United States and has no known cure.

"Building a baby's brain during pregnancy involves creating a cortex that contains six layers," said co-author Eric Courchesne, professor of neurosciences and director of the Autism Centre of Excellence at University of California, San Diego.

"We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism."

For the study, researchers dissected brain tissue from 11 children, aged two to 15, who had been diagnosed with autism spectrum disorder (ASD) and who had died, most of them by drowning.

Looking for a specific set of 25 genes that had "robust, consistent, and specific expression patterns in the cortex," they compared them to brain samples from 11 children without autism, said the study.

Researchers found that 91 per cent of the autistic brains were lacking — or showed an unusual pattern — of the expected genetic markers in several layers of the cortex.

The signs of disorganisation were found in patches across the different layers of the frontal and temporal lobes of the brain, the parts that are responsible for social function, communication, emotions and language.

"The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder," said co-author Ed Lein of the Allen Institute for Brain Science in Seattle.

Researchers said they still don't understand why these changes come about in some children, apparently leading to autism, but not in others.

The patchwork nature of the defects does, however, provide a clue as to why autism can affect people in various degrees, from severe to mild disabilities.

It also may explain why some children respond to intensive therapy and become better communicators when identified early, since the brain may be able to rewire some connections to overcome the areas that are not working.

"While autism is generally considered a developmental brain disorder, research has not identified a consistent or causative lesion," said Thomas Insel, director of National Institute for Mental Health, which funded the study.

"If this new report of disorganised architecture in the brains of some children with autism is replicated, we can presume this reflects a process occurring long before birth."

The same research team had previously found that the brains of children with autism were heavier than other children's, and that they had more neurons in the prefrontal cortex.

The brains sampled for this study "represented nearly the entirety of tissue suitable for study at the Brain and Tissue Bank for Developmental Disorders at the National Institute of Child Health and Human Development and the Harvard Brain Tissue Resource Centre," said the article.

Still, the fact that only 11 were studied means that more research is necessary, said Andrew Adesman, chief of developmental and behavioural paediatrics at Steven & Alexandra Cohen Children's Medical Centre of New York.

"This study would have been stronger if they had a larger sample and included a group of children who had neurologic deficits but not autism," said Adesman, who was not involved with the research.

He nevertheless described the team's techniques for identifying microscopic brain abnormalities as "extremely sophisticated."

While some of the physical brain changes in autism were already known to science, the latest research provides a more detailed look at how this happens.

"This study is particularly important as it points to the potential role of several genes involved in the specification of distinct cortical layers during early brain development," said Patrick Hof, vice-chair of the Fishberg Department of Neuroscience, Friedman Brain Institute, and Seaver Autism Centre at the Icahn School of Medicine at Mount Sinai.

Research like this "can provide us with crucial clues to develop novel therapeutic strategies toward a cure," he said.

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