Autism spectrum disorder is
characterized by impaired social interactions and other cognitive and
behavioral problems. According to the Centers for Disease Control and Prevention, about
1.5% of children in the United States have autism.
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.
‘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.’
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
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
The findings, published 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."
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.
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
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.