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Autism
begins in pregnancy, according to study: Cortical layers disrupted during brain
development in autism
Autism
begins in pregnancy, according to study: Cortical layers disrupted during brain
development in autism
Date:
March 26,
2014
Source:
University of California, San Diego
Health Sciences
Summary:
Researchers have published a study that gives clear
and direct new evidence that autism begins during pregnancy. The researchers
analyzed 25 genes in post-mortem brain tissue of children with and without
autism. These included genes that serve as biomarkers for brain cell types in
different layers of the cortex, genes implicated in autism and several control
genes.
............................
Researchers
at the University of California, San Diego School of Medicine and the Allen
Institute for Brain Science have published a study that gives clear and direct
new evidence that autism begins during pregnancy.
The study
will be published in the March 27 online edition of the New England Journal
of Medicine.
The
researchers -- Eric Courchesne, PhD, professor of neurosciences and director of
the Autism Center of Excellence at UC San Diego, Ed S. Lein, PhD, of the Allen
Institute for Brain Science in Seattle, and first author Rich Stoner, PhD, of
the UC San Diego Autism Center of Excellence -- analyzed 25 genes in
post-mortem brain tissue of children with and without autism. These included
genes that serve as biomarkers for brain cell types in different layers of the
cortex, genes implicated in autism and several control genes.
"Building
a baby's brain during pregnancy involves creating a cortex that contains six
layers," Courchesne said. "We discovered focal patches of disrupted
development of these cortical layers in the majority of children with
autism." Stoner created the first three-dimensional model visualizing
brain locations where patches of cortex had failed to develop the normal
cell-layering pattern.
"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," explained Lein.
During early
brain development, each cortical layer develops its own specific types of brain
cells, each with specific patterns of brain connectivity that perform unique
and important roles in processing information. As a brain cell develops into a
specific type in a specific layer with specific connections, it acquires a
distinct genetic signature or "marker" that can be observed.
The study
found that in the brains of children with autism, key genetic markers were
absent in brain cells in multiple layers. "This defect," Courchesne
said, "indicates that the crucial early developmental step of creating six
distinct layers with specific types of brain cells -- something that begins in
prenatal life -- had been disrupted."
Equally
important, said the scientists, these early developmental defects were present
in focal patches of cortex, suggesting the defect is not uniform throughout the
cortex. The brain regions most affected by focal patches of absent gene markers
were the frontal and the temporal cortex, possibly illuminating why different
functional systems are impacted across individuals with the disorder.
The frontal
cortex is associated with higher-order brain function, such as complex
communication and comprehension of social cues. The temporal cortex is
associated with language. The disruptions of frontal and temporal cortical
layers seen in the study may underlie symptoms most often displayed in autistic
spectrum disorders. The visual cortex -- an area of the brain associated with
perception that tends to be spared in autism -- displayed no abnormalities.
"The
fact that we were able to find these patches is remarkable, given that the
cortex is roughly the size of the surface of a basketball, and we only examined
pieces of tissue the size of a pencil eraser," said Lein. "This
suggests that these abnormalities are quite pervasive across the surface of the
cortex."
Data
collected for the Allen Brain Atlas, as well as the BrainSpan Atlas of the
Developing Human Brain was developed by a consortium of partners and funded by
the National Institute of Mental Health. It allowed scientists to identify
specific genes in the developing human brain that could be used as biomarkers
for the different layer cell types.
Researching
the origins of autism is challenging because it typically relies upon studying
adult brains and attempting to extrapolate backwards. "In this case,"
Lein noted, "we were able to study autistic and control cases at a young
age, giving us a unique insight into how autism presents in the developing
brain."
"The
finding that these defects occur in patches rather than across the entirety of
cortex gives hope as well as insight about the nature of autism," added
Courchesne.
According to
the scientists, such patchy defects, as opposed to uniform cortical pathology,
may help explain why many toddlers with autism show clinical improvement with
early treatment and over time. The findings support the idea that in children
with autism the brain can sometimes rewire connections to circumvent early
focal defects, raising hope that understanding these patches may eventually
open new avenues to explore how that improvement occurs.
Additional
contributors to the study include Maggie L. Chow, PhD, and Subhojit Roy, MD, PhD,
UC San Diego; Maureen P. Boyle, PhD, UC San Diego and Allen Institute; Peter R.
Mouton, PhD, University of South Florida School of Medicine; Anthony
Wynshaw-Boris, MD, PhD, Case Western Reserve University School of Medicine; and
Sophia A. Colamarino, PhD, Stanford University School of Medicine.
This
research was supported by funds from the Simons Foundation, the Peter Emch
Family Foundation, Cure Autism Now/Autism Speaks, the Thursday Club Juniors,
the UC San Diego Autism Center of Excellence (NIMH grant P50-MH081755), and the
Allen Institute for Brain Science (NIMH grant RC2MH089921).
Story
Source:
The above
story is based on materials provided by University of California, San Diego Health Sciences.
Note: Materials may be edited for content and length.
Journal
Reference:
- Rich Stoner, Maggie L. Chow, Maureen P. Boyle, Susan M. Sunkin, Peter R. Mouton, Subhojit Roy, Anthony Wynshaw-Boris, Sophia A. Colamarino, Ed S. Lein, Eric Courchesne. Patches of Disorganization in the Neocortex of Children with Autism. New England Journal of Medicine, 2014; 370 (13): 1209 DOI: 10.1056/NEJMoa1307491
Cite This
Page:
University of California, San Diego
Health Sciences. "Autism begins in pregnancy, according to study: Cortical
layers disrupted during brain development in autism." ScienceDaily.
ScienceDaily, 26 March 2014.
<www.sciencedaily.com/releases/2014/03/140326181909.htm>.
