Do autism begin before birth? New Engl Jl Med March 2014


Autism is associated with many cortical defects. Macroscopic early brain overgrowth is reported in  majority of cases. Autistic children  between the ages of 2 and 16 years have abnormally heavy brains and  have a relative increase of 67% in the overall number of neurons in the prefrontal cortex. Several cortical and subcortical regions show  defects  and dysfunction. Abnormal expression of genes and gene pathways that govern neuronal cell-cycle regulation , DNA integrity, cell differentiation, and cortical patterning in the prefrontal cortex is observed in autism. Evidence strongly suggest that autism is a neuro developmental disorder ( like lissencephaly, polymicrogyria, schizencephaly, and other  several cortical heterotopias that arise from defects in cell-cycle processes).

Neuropathological studies so far are from brains of adult autism sufferers. Molecular, cellular, and organisational anomalies that are present in the brains of children with autism remain largely unstudied.Rich Stone and team of researchers examined the neocortical architecture during the early years after the onset of autism using RNA in situ hybridization with a panel of  molecular markers to phenotype cortical microstructure. 


42 fresh-frozen postmortem cortical tissue blocks (1 to 2 cm3 ) from children (2 to 15 years of age) with autism  were studied against controls. They found focal patches of abnormal laminar cytoarchitecture and cortical dis- organization of neurons, but not glia, in prefrontal and temporal cortical tissue . These patches were identified in both dorsolateral prefrontal cortex (in 10 of 11 case samples) and posterior superior temporal cortex.   Clearest signs of such abnormal expression were seen in cortical layers 4 and 5.  No two patches were identical in presentation. A deficit in the expression of markers of excitatory cortical neurons was the most robust indicator of a patch region. Authors infer that regions of focal patches were not the result of a reduced number of neurons.

Presence of discrete pathological patches of abnormal laminar cytoarchitecture and disorganization in the  samples of prefrontal and temporal cortexes is consistent with an early prenatal origin of autism or at least prenatal processes that may confer a predisposition to autism. Laminar disorganization could result from migration defects resulting in the failure of cells to reach their targeted destination and the accumulation of such cells in nearby regions. Patches could also reflect de novo changes early in neurodevelopmental processes, potentially in gene sequence or epigenetic state, where some progenitor cells are affected.

These patches occurred in regions mediating the functions that are disturbed in autism: ( social, emotional, communication, and language).  These disorganized patches in different locations would be disrupting various  functional systems  and thus determine/ influence symptom expression, response to treatment, and clinical outcome.

Comments: This study reinforces the importance of early identification and intervention. The patchy nature may explain why some young children with autism show signs of improvement if treated early enough. One may also hope that the plastic infant brain may have a chance of rewiring itself to compensate for these changes.
Summary of the article: Patches of disorganisation in the neocortex of children with autism.Stoner R, Chow ML, Boyle MP, Sunkin SM, Mouton PR, Roy S, Wynshaw-Boris A, Colamarino SA, Lein ES, Courchesne E. N Engl J Med. 2014 Mar 27;370(13):


Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s