Study identifies gene expression abnormalities in autism

March 22, 2012
This is Eric Courchesne, Ph.D., of the UC San Diego Autism Center for Excellence. Credit: UC San Diego School of Medicine

A study led by Eric Courchesne, PhD, director of the Autism Center of Excellence at the University of California, San Diego School of Medicine has, for the first time, identified in young autism patients genetic mechanisms involved in abnormal early brain development and overgrowth that occurs in the disorder. The findings suggest novel genetic and molecular targets that could lead to discoveries of new prevention strategies and treatment for the disorder.

The study to be published on March 22 in uncovered differences in gene expression between from young (2 to14 years old) and adult individuals with autism syndrome disorder, providing important clues why and development is abnormal in this disorder.

Courchesne first identified the link between early brain overgrowth and autism in a landmark study published by the (JAMA) in 2003. Next, he tested the possibility that brain overgrowth might result from an abnormal excess of brain cells. In November 2011, his study, also published in JAMA, discovered a 67 percent excess of brain cells in a major region of the brain, the – a part of the brain associated with social, communication and cognitive development.

"Our next step was to see whether there might be abnormalities of genetic functioning in that same region that might give us insight into why there are too many cells and why that specific region does not develop normally in autism," said Courchesne.

In the new study, the researchers looked towards genes for answers, and showed that genetic mechanisms that normally regulate the number of cortical neurons are abnormal. "The genes that control the number of brain cells did not have the normal functional expression, and the level of gene expression that governs the pattern of neural organization across the prefrontal cortex is turned down. There are abnormal numbers and patterns of brain cells, and subsequently the pattern is disturbed," Courchesne said. "This probably leads to too many in some locations, such as prefrontal cortex, but perhaps too few in other regions of cortex as well."

In addition, the scientists discovered a turning down of the responsible for detecting DNA defects and correcting or removing affected cells during periods of rapid prenatal development.

Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings in the brain at young ages have remained largely unknown. Until now, few studies have been able to investigate whole-genome gene expression and genotype variation in the brains of young patients with autism, especially in regions such as the prefrontal cortex that display the greatest growth abnormality.

Scientists – including co-first authors Maggie Chow, PhD, and Tiziano Pramparo, PhD, at UC San Diego – identified abnormal brain gene expression patterns using whole-genome analysis of mRNA levels and copy number variations from 33 autistic and control postmortem brain samples. They found evidence of dysregulation in the pathways that govern cell number, cortical patterning and cell differentiation in the young autistic prefrontal cortex. In contrast, in adult patients with autism, the study found that this area of the brain shows dysregulation of signaling and repair pathways.

"Our results indicate that gene expression abnormalities change across the lifespan in autism, and that dysregulated processes in the developing brain of autistic patients differ from those detected at adult ages," said Courchesne. "The dysregulated genetic pathways we found at young ages in autism may underlie the excess of neurons – and early overgrowth – associated with this disorder."

Explore further: Autism linked with excess of neurons in prefrontal cortex

Related Stories

Autism linked with excess of neurons in prefrontal cortex

November 8, 2011
A study by researchers at the University of California, San Diego Autism Center of Excellence shows that brain overgrowth in boys with autism involves an abnormal, excess number of neurons in areas of the brain associated ...

Study characterizes epigenetic signatures of autism in brain tissue

November 7, 2011
Neurons in the prefrontal cortex of individuals with autism show changes at numerous sites across the genome, according to a study being published Online First by the Archives of General Psychiatry.

Autism blurs distinctions between brain regions

June 3, 2011
Autism blurs the molecular differences that normally distinguish different brain regions, a new study suggests. Among more than 500 genes that are normally expressed at significantly different levels in the front versus the ...

Study finds autism-related early brain overgrowth slows by age 2 years

May 2, 2011
Scientists using magnetic resonance imaging (MRI) observed that the brains of children with autism spectrum disorder are larger than those without autism, but this difference appears related to increased rates of brain growth ...

Autism risk gene linked to differences in brain structure

March 21, 2012
Healthy individuals who carry a gene variation linked to an increased risk of autism have structural differences in their brains that may help explain how the gene affects brain function and increases vulnerability for autism. ...

Weaker brain 'sync' may be early sign of autism

June 22, 2011
In a novel imaging study of sleeping toddlers, scientists at the University of California, San Diego Autism Center of Excellence report that a diminished ability of a young brain's hemispheres to "sync" with one another could ...

Recommended for you

Signaling pathway may be key to why autism is more common in boys

October 17, 2017
Researchers aiming to understand why autism spectrum disorders (ASD) are more common in boys have discovered differences in a brain signaling pathway involved in reward learning and motivation that make male mice more vulnerable ...

Whole genome sequencing identifies new genetic signature for autism

October 12, 2017
Autism has genetic roots, but most cases can't be explained by current genetic tests.

Mum's immune response could trigger social deficits for kids with autism

October 10, 2017
The retrospective cohort study of 220 Australian children, conducted between 2011-2014, indicates that a "an immune-mediated subtype" of autism driven by the body's inflammatory and immunological systems may be pivotal, according ...

Largest study to date reveals gender-specific risk of autism occurrence among siblings

September 25, 2017
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Faulty cell signaling derails cerebral cortex development, could it lead to autism?

September 20, 2017
As the embryonic brain develops, an incredibly complex cascade of cellular events occur, starting with progenitors - the originating cells that generate neurons and spur proper cortex development. If this cascade malfunctions ...

Predicting atypical development in infants at high risk for autism?

September 12, 2017
New research from the Sackler Institute for Developmental Psychobiology at Columbia University Medical Center (CUMC) identifies a potential biomarker that predicts atypical development in 1- to 2-month-old infants at high ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.