Autism: Defective Genes May Explain Uncontrolled Brain Growth

As a baby grows inside the womb, its brain does not simply expand like a dehydrated sponge dropped in water.

Early brain development is an elaborate procession. Every minute some 250,000 neurons bloom, squirming past one another like so many schoolchildren rushing to their seats at the sound of the bell.

Each neuron grows a long root at one end and a crown of branches at the other, linking itself to fellow cells near and far.

By the end of the second trimester, neurons in the baby's brain have formed trillions of connections, many of which will not survive into adulthood—the least traveled paths will eventually wither.

Sometimes, the developing brain blunders, resulting in "neuro-developmental disorders," such as autism.

But exactly why or how early cellular mistakes cause autism has eluded medical science. Now, Eric Courchesne of the University of California, San Diego, thinks he has linked atypical gene activity to excessive growth in the autistic brain.

With the new data, he has started to trace a cascade of genetic and cellular changes that he thinks define autism.

Although intrigued by Courchesne's work, other researchers caution that explosive neural growth is not necessarily a defining feature of all autistic brains.

Since 1998 Courchesne has been searching autistic brains for unusual structural features.

His studies suggest that while in the womb, the autistic brain sprouts an excess of neurons and continues to balloon during the first five years of life, as all those extra neurons grow larger and form connections.

Sometime after age four or five, Courchesne has also found, autistic brains actually start to lose neural connections, faster than typical brains.

In a study published November 2011 in JAMA, The Journal of the American Medical Association, Courchesne reported that children with autism have 67 percent more neurons in their prefrontal cortex (PFC) than typical children.

Located in the area of the brain just behind the eyes, the PFC is responsible for what psychologists call "executive functions"—high-level thinking, such as planning ahead, inhibiting impulses and directing attention. In his 2011 study Courchesne sliced up brain tissue from six autistic children and seven typical children who had passed away and counted the number of cell bodies in the sections to estimate the total number of neurons in their PFCs.

Now, Courchesne and his colleagues have analyzed DNA and RNA in 33 cubes of brain tissue from people who passed away, 15 of whom were autistic (nine children and six adults) and 18 who had typical brains (seven children and 11 adults).

Looking at the order of DNA's building blocks reveals whether individual genes have mutations; measuring levels of RNA indicates how often those genes were translated into proteins.

Such gene expression, Courchesne and his colleagues found, varied between autistic and typical brains.

In brain tissue from both autistic children and autistic adults, genes coding for proteins that identify and repair mistakes in DNA were expressed at unusually low levels.

Additionally, all autistic brains demonstrated unusual activity levels for genes that determine when neurons grow and die and how newborn neurons migrate during early development.

Some genes involved in immune responses, cell-to-cell communication and tissue repair, however, were expressed at unusual levels in adult autistic brains, but not in autistic children's brains.

The results appear in the March 22 issue of PLoS Genetics.

You can also Read More of this article here at Scientific American: The Ballooning Brain