Pediatrics Xagena

Children with autism: patches of disorganization in the neocortex

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.

To systematically examine neocortical architecture during the early years after the onset of autism, researchers used RNA in situ hybridization with a panel of layer- and cell-type–specific molecular markers to phenotype cortical microstructure.

Investigators 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.

Focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons were observed, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children.

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, was seen.

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.

In this small, explorative study, researchers have found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism.
The data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. ( Xagena )

Stoner R et al, N Engl J Med 2014; 370:1209-1219