Yale team finds clues to origin of autism

Finding major new clues to the origins of autism, a Yale-led team of researchers has pinpointed which cell types and regions of the developing human brain are affected by gene mutations linked to autism. They report their findings in the Nov. 21 issue of the journal Cell.

Analyzing massive amounts of gene expression data generated by the BrainSpan project, the team identified common neural circuits affected by autism-risk genes and when, where, and in what cell types those genes exert their effects on the developing human brain and lead to autism spectrum disorders.

Although other genes and neural circuits that contribute to autism spectrum still remain to be found, the new findings suggest new targeted treatments for autism may be possible, said Nenad Sestan, professor of neurobiology, investigator for Kavli Institute for Neuroscience at Yale, and co-senior author of the paper.

"We know now that we may not have to treat the whole brain, that changes related to mutations in autism-risk genes may affect particular neural circuits at specific places at specific times," Sestan said.

The genetic causes of autism, like other complex diseases such as schizophrenia, have proved daunting to study. Several hundred genes have already been linked to autism spectrum disorders, but no single gene seems to account for the symptoms of the disorders. The task of searching for a cause for the disorder is the scientific equivalent of trying to reach an unknown town in Maine knowing only that you started from a street in San Diego.

The Yale team led by Sestan and Matthew State, now at the University of California-San Francisco, together with James Noonan of Yale School of Medicine, Bernie Devlin of the University of Pittsburgh, and Kathryn Roeder of Carnegie-Mellon University tackled the difficulty by searching for molecular crossroads shared by nine genes conclusively linked to autism. An analysis of when and where nine of those autism genes are most co-activated identified at least two such molecular crossroads. The first influence a specific cell type - excitatory projection neurons - and their neural circuits, which form and become active about three to five months after conception. The second implicates the mid-fetal frontal cortex, a brain region critical for cognition, language, and complex motor behaviors.

The history of autism Abstract Autism remains a fascinating condition, perhaps the most prolifically researched of all child psychiatric disorders. Its history yields many lessons: early accounts of possible autism are, with one exception, unclear; the greatest contributions to our understanding have come from individual clinicians and researchers; the concept and definition of the disorder have changed greatly over the years; some ideas once held with conviction, were later proved to be unfounded; and socio-political shifts as well as research findings have radically altered our understanding of the syndrome as well as the care and treatment offered to people with autism.