In this issue of JAMA, the report by Courchesne and colleagues1 documents an increase in neuron number in the prefrontal cortex (PFC) in male children and adolescents with autism. Those findings build on Leo Kanner's original observations2 in 1943 and 2 decades of recent research investigating macrocephaly in autism. Macrocephaly occurs in 20% of individuals with autism on average and is usually due to megalencephaly—abnormal enlargement of the brain during childhood.3 The enlargement is rarely present at birth; it develops during early childhood when head growth accelerates during the first 18 months of life.4 Mean total brain, lobar, white matter, and gray matter volumes, including volume of the cortex, are significantly increased by 2 to 3 years of age in children with autism when compared with typically developing and also nonautistic developmentally delayed individuals.5- 7 The excessive head growth and brain growth occur prior to most clinical manifestations of the disorder, raising the possibility that the mechanisms that cause excessive growth also play a role in the primary developmental neuropathology of autism.
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