New Evidence on the Prenatal Origin of Autism

More and more evidence points to a genetic basis for autism. It is unclear what exactly causes genes to generate these alterations in brain formation so they affect some of its areas. It is hypothesized that these genetic alterations have an environmental origin, and every day we find more evidence of how certain chemical compounds, both by themselves and in combinations – affect the body and alter the genetic quality, and therefore inheritance. But what is more and more apparent is that autism has a prenatal origin, i.e. the child is born with a series of changes that will cause the visible signs of autism to appear to a greater or lesser extent.

A team of researchers from the University of California San Diego School of Medicine, and the Allen Institute for Brain Science have conducted a study (1) on brain tissue to try to find structural differences between the brains of people with autism compared to people without any disorder. For this purpose they focused on the study of the prefrontal cortex, located on the outer region of the brain. This brain area was chosen because it is one of the first that develops. This area builds on 6 layers that are shaped during development of the baby in the womb. And during that process, each cortical layer develops its own specific types of brain cells, each cell type is constructed based on a genetically predefined pattern and form the cerebral network that will be responsible for brain connectivity, which among other functions processes information.

Because the cortex is formed before birth, the results suggest that autism starts in the womb, the researchers say. “The results suggest that between the second and third quarter,” said lead researcher Eric Courchesne, a professor of neuroscience at the University of California, San Diego.

Neocortex patch sign of autism

Post-mortem brain tissue analysis revealed areas of disorganized neurons as spots. The arrows show the decrease or lack of expression of genetic markers in a spot through multiple layers of the dorsolateral prefrontal cortex. Photo: Rich Stoner, Ph.D., University of California, San Diego

These genetic patterns are a signature or specific marker for each type of brain cells, and therefore each layer displays a genetic pattern that is visible in the conformation of the structure. And certain key markers were not found in samples of tissue from children with autism.

And this is where the researchers found the greatest differences. In the study, researchers examined post-mortem brain tissue samples from 22 children aged 2 to 15 years old, 11 with autism and 11 without the disorder, and detected small areas of arrested development scattered throughout the outer layers of the brain (neocortex) of children with autism, a direct evidence of prenatal origin. That is to say, during the prenatal development process of the brain, there occurs an alteration observed in focal patches mainly in the frontal and temporal areas.

If we consider that the frontal cortex is associated with higher-order functions of the brain, such as communication and understanding complex social cues, whereas the temporal cortex is associated with language, the discovery suggests these are precisely two of the areas most affected in autism. However, the visual cortex, a brain area associated with perception, showed no abnormalities, even though there exists a body of evidence about visual disturbances in autism. However, to the extent that the connection between these different areas presents alterations, this implies there will be alterations in the way information is processed, conducting thus to altered sensory perception issues, which in turn leads to the the global information processing to present alterations.

One aspect that struck the researchers is that the spots vary in severity and location. This may explain the wide range of symptoms seen in the disorder. The study found that in 10 of the 11 samples of children with autism, markers of several layers of the cortex were absent, compared with only 1 of the 11 control samples. In addition, these symptoms are not spread throughout the brain surface, but are located in focal spots 5-7 mm (0.20 to 0.28 inches) long and spanning multiple cortical layers. Considering the size of the cerebral cortex is the size of a basketball, this finding becomes even more important.

But also, being able to identify genes involved in the processes of creation of the brain, it means that a door opens to trace the origin of the genetic error that generates this alteration, and even use it as a biomarker in the not too distant future to help develop a clinical test for the immediate detection of the presence or absence of autism, long before the onset of the first signs, and therefore to prevent its occurrence.

3D Recreation

In turn, this research gives us a key to understanding why the neuronal pruning that usually occurrs around six months of age in the brain of babies, does not happen in boys with autism, and causes the brain of children with autism to have a larger size.

The researchers say these irregular defects, unlike the uniform cortical pathology may help explain why many children with autism show clinical improvement with early treatment and in time. That is, an early intervention could force the brain to seek alternative routes or even to repair faulty connections by circumventing the damaged areas. This also would explain how some children manage to have so many advances and even go out the spectrum, after an intensive early intervention and aimed at improving the core deficits of autism, increasing the hope that understanding these alterations may open new avenues to explore how such improvement occurs.

Although the study sample is small and it is important that this study be replicated with a larger number of samples, the result has sufficient coherence to open a new path of research with a much more defined method and knowing exactly what one needs to search for.

1. 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

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