Autism begins in the womb: Study shows early development of the brain is disrupted in children with the condition
Researchers in California discovered that there are patches of disrupted development in the cortices of children with autism.
Autism could begin in the womb, new research shows.
U.S. scientists say they have new evidence to suggest that the developmental disability begins in early pregnancy.
Their findings indicate that the early development of the brain’s cortex - the outermost layered structure of neural tissue - is disrupted in children with autism.
Researchers at the University of California, San Diego School of Medicine and the Allen Institute for Brain Science analysed 25 genes in the brain tissue of dead children.
Some of these had autism, and others did not.
They looked at 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,’ Dr Eric Courchesne, professor of neurosciences and director of the Autism Center of Excellence at UC San Diego, said.
‘We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism.’
‘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,’ added Dr Ed Lein from of the Allen Institute for Brain Science in Seattle.
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 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,’ Dr 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 disruption of the development of the cortex occurs while the child is still in the womb
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 Dr Lein. ‘This suggests that these abnormalities are quite pervasive across the surface of the cortex.’
The researchers say that researching the origins of autism is challenging because it typically relies on studying adult brains and attempting to extrapolate backwards.
‘In this case,’ Dr Lein said, ‘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 Dr 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.
The research is published in the New England Journal of Medicine.
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ORIGINAL ARTICLE> http://www.nejm.org/doi/full/10.1056/NE ... tured_home
Patches of Disorganization in the Neocortex of Children with Autism
Rich Stoner, Ph.D., Maggie L. Chow, Ph.D., Maureen P. Boyle, Ph.D., Susan M. Sunkin, Ph.D., Peter R. Mouton, Ph.D., Subhojit Roy, M.D., Ph.D., Anthony Wynshaw-Boris, M.D., Ph.D., Sophia A. Colamarino, Ph.D., Ed S. Lein, Ph.D., and Eric Courchesne, Ph.D.
N Engl J Med 2014; 370:1209-1219March 27, 2014DOI: 10.1056/NEJMoa1307491
BACKGROUND
Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development.
METHODS
To systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type–specific molecular markers to phenotype cortical microstructure. We assayed markers for neurons and glia, along with genes that have been implicated in the risk of autism, in prefrontal, temporal, and occipital neocortical tissue from postmortem samples obtained from children with autism and unaffected children between the ages of 2 and 15 years.
RESULTS
We observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches.
CONCLUSIONS
In this small, explorative study, we found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. (Funded by the Simons Foundation and others.)
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26 Mar 2014, 6:21 pm
