Autism Changes Molecular Structure Of The Brain

Autism is a complex brain disorder that strikes in early childhood. The disease disrupts a child's ability to communicate and develop social relationships and is often accompanied by acute behavioral challenges. In the United States, autism spectrum disorders are diagnosed in one in 110 children — and one in 70 boys. Diagnoses have expanded tenfold in the last decade.

For decades, autism researchers have faced a baffling riddle: how to unravel a disorder that leaves no known physical trace as it develops in the brain. Now a UCLA study is the first to reveal how the disorder makes its mark at the molecular level, resulting in an autistic brain that differs dramatically in structure from a healthy one. The discovery also identifies a new line of attack for researchers, who currently face a vast array of potential fronts for tackling the neurological disease and identifying its diverse causes. 

 "If you randomly pick 20 people with autism, the cause of each person's disease will be unique," said principal investigator Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics and a professor of neurology and psychiatry at the David Geffen School of Medicine at UCLA. "Yet when we examined how genes and proteins interact in autistic people's brains, we saw well-defined shared patterns. This common thread could hold the key to pinpointing the disorder's origins."

 The research team, led by Geschwind, included scientists from the University of Toronto and King's College London. They compared brain tissue samples obtained after death from 19 autism patients and 17 healthy volunteers. After profiling three brain areas previously linked to autism, the group zeroed in on the cerebral cortex, the most evolved part of the human brain. 

The researchers focused on gene expression — how a gene's DNA sequence is copied into RNA, which directs the synthesis of cellular molecules called proteins. Each protein is assigned a specific task by the gene to perform in the cell. By measuring gene-expression levels in the cerebral cortex, the team uncovered consistent differences in how genes in autistic and healthy brains encode information. 

The researchers' next step was to identify the common patterns. To do this, they looked at the cerebral cortex's frontal lobe, which plays a role in judgment, creativity, emotions and speech, and at its temporal lobes, which regulate hearing, language and the processing and interpreting of sounds.  When the scientists compared the frontal and temporal lobes in the healthy brains, they saw that more than 500 genes were expressed at different levels in the two regions. In the autistic brains, these differences were virtually non-existent.