Scientists have found clear and direct new evidence that autism begins during pregnancy.
Researchers at the University of California, San Diego School of Medicine and the Allen Institute for Brain Science analysed 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," said Eric Courchesne, professor of neurosciences and director of the Autism Center of Excellence at UC San Diego.
"We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism," he said.
First author of the study Rich Stoner, of the UC San Diego Autism Center of Excellence created the first three-dimensional model visualising brain locations where patches of cortex had failed to develop the normal cell-layering pattern.
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 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," Courchesne said.
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, researchers said.
The visual cortex - an area of the brain associated with perception that tends to be spared in autism - displayed no abnormalities.