Surprising Findings in Autism: Insights into Anthropogeny?

Although the neurobiology of autism has been studied for more than two decades, the majority of studies have examined brain anatomy 10 or more years after the onset of clinical symptoms. The early neural defects that cause autism remain unknown, but their signature is likely to most evident during the first years of life when clinical symptoms are emerging. This lecture highlights several new findings about the neural and genomic abnormalities in autism at young ages. It contrasts brain pathology at young ages versus adult ages in autism. Evidence supports three phases of brain development pathology in autism: a phase of early brain overgrowth in some percentage of toddlers, then arrest of growth and finally degeneration in some percentage of cases. Early brain overgrowth, which is present in a large percentage of cases, may be a key to discovering the neural bases for emergence of autistic behavior as well as its genetic and non-genetic causes. We discovered that excess neuron number is one cause of early brain overgrowth, and abnormal cortical patterning. Gene expression results also point to abnormal cortical patterning during development. Such abnormalities in cortical patterning and wiring may lead to exuberant local and short distance cortical interactions impeding the function of long-distance interactions between brain regions. Since large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations in autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional and communication functions that epitomize humans.