Researchers have discovered that the brains of people with autism can be dramatically different in molecular structure than those of healthy people, a finding that may help scientists better pinpoint the causes of this varied neurological disorder.
"If you randomly pick 20 people with autism, the cause of each person's disease will be unique," said principal investigator Daniel Geschwind, chair of human genetics at the University of California, Los Angeles. "Yet when we examined how genes and proteins interact in autistic people's brains, we saw well-defined shared patterns. This common thread could hold the key to pinpointing the disorder's origins."
Autism is a complex brain disorder that strikes at an early age, disrupting a child's ability to communicate and develop social relationships and often marked by repetitive behaviours or mannerisms. In North America, one in 110 children has some form of autism spectrum disorder, which is far more prevalent in boys than girls. The number of cases has multiplied tenfold over the last decade.
Dr. Geschwind's team, which included scientists from the University of Toronto and King's College in London, compared brain tissue samples obtained after death from 19 patients with autism spectrum disorder and 17 healthy volunteers.
The scientists, whose study is published in Thursday's edition of the journal Nature, focused on gene expression in the cerebral cortex, the most evolved part of the human brain. What they discovered was consistent differences in how genes in autistic and healthy brains encode information.
But they also found similar gene expression patterns in most, though not all, of the brains of people with autism - a surprising finding given the wide variability of the condition.
"So you wouldn't necessarily expect that, and yet that's what we saw," Dr. Geschwind said from Los Angeles. "So we saw this common signal."
The scientists also looked at common patterns in the key segments of the cerebral cortex: the frontal lobe, the centre for judgment, creativity, emotions and speech; and the temporal lobe, which regulates hearing, language and the processing and interpretation of sound.
Dr. Geschwind said a comparison of frontal and temporal lobes in healthy brains showed a 500-plus difference in genes expressed between the two brain regions.
But in the autistic brains, "we only saw eight," he said.
"In a healthy brain, hundreds of genes behave differently from region to region, and the frontal and temporal lobes are easy to tell apart," Dr. Geschwind added. "We didn't see this in the autistic brain. Instead, the frontal lobe closely resembles the temporal lobe. Most of the features that normally distinguish the two regions had disappeared."
Dr. Geschwind said many of the genes involved are neurodevelopmental genes, which are expressed during fetal growth midway through gestation.
"So that's telling us that there is certainly a developmental component to [autism] a very early developmental component. That aspect of it looks like it would certainly be going on in utero."
That's not to say that environmental factors don't also play a role in the development of autism in a child, but the exact link is far from being identified, he added.
Daniel Goldowitz, Canada Research Chair in Developmental Neurogenetics at the University of British Columbia, said the research provides new and important molecular insights into the disorder.
"I think it's actually very optimistic … because what they find is that development has not progressed in the autistic brain like it has in the normal brain," he said Wednesday from Vancouver. "To some extent, what I would get out of this paper is that the genetic architecture that supports brain development and function has been underutilized."
But because the human brain has the capacity to make new connections that increase or improve function - what's known as plasticity - Dr. Goldowitz said it's possible that drug or cognitive interventions might be developed to overcome developmental deficits that lead to autistic behaviours.
Dr. Goldowitz is heading a project to map the genes of the cerebellum to see which ones are activated and essential for brain development, so researchers can better understand such diseases as autism and schizophrenia. Identifying those genes could lead to ways of encouraging plasticity, the brain's ability to heal and change.
For Dr. Geschwind, the next step in his research is to analyze brain tissue from other deceased autism patients and healthy subjects and to expand the number of brain regions examined to see if there are other differences.
"So one thing we'd want to do is see how widespread are these findings throughout the brain," he said. "We've only looked at two cortical regions. You'd want to look at many more."
The study was funded by the U.S. National Institute of Mental Health, the Canadian Institutes of Health Research and Genome Canada.
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