12 February 2010

Researchers tracking autism's roots

by Kate Melville

New research has found that in fragile X syndrome - a genetic defect that is the best-known cause of autism - there is delayed development of the sensory cortex, the part of the brain that responds to touch, which researchers speculate may trigger a domino effect and cause further problems with the wiring of the brain. Understanding how and when the function of the brain is affected in fragile X offers a target for a therapy to fix the incorrect development.

"There is a 'critical period' during development, when the brain is very plastic and is changing rapidly," said Northwestern University's Anis Contractor, the lead investigator of the study. "All the elements of this rapid development have to be coordinated so that the brain becomes wired correctly and therefore functions properly."

Fragile X syndrome is caused by a gene mutation in the X chromosome that interferes in the production of a protein called fragile X mental retardation protein (FMRP). That protein directs the formation of other proteins that build synapses in the brain. People with fragile X are missing FMRP. It's as if the foreman is missing on the brain's key construction site. Fragile X is so named because the X chromosome appears broken or kinked.

Reporting in the journal Neuron, the researchers explain how they worked with a mouse model of fragile X and found the development of synapses, the sites where neurons communicate with each other, was delayed in the sensory cortex. "The critical period may provide a window during which therapeutic intervention can correct synaptic development and reverse some of the symptoms of the disease," Contractor said.

People with fragile X have debilitating sensory as well as cognitive problems. "They have tactile defensiveness," Contractor explained. "They don't look in people's eyes, they won't hug their parents, and they are hypersensitive to touch and sound. All of this causes anxiety for family and friends as well as for the fragile X patients themselves. Now we have the first understanding of what goes wrong in the brain."

The sensory overload in people with fragile X results in social withdrawal, hyperarousal and anxiety. It shows up in early infancy and progressively worsens throughout childhood. Boys are more severely affected by fragile X because they have only one X chromosome. Girls, who have two X chromosomes, are less affected by the defect.

Contractor's team discovered the sensory cortex was late to mature by recording the electrical signals flowing through synapses. This provided a snapshot of when and how this part of the brain was developing. The ability of the brain to correctly process incoming information is based on the correct development of these synapses, he noted.

"[The research] starts to build a framework for how this part of the cortex actually develops," Contractor said. "Our next step is to work out what is going wrong. How does elimination of this gene FMR1 disrupt the normal developmental processes?"

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Source: Northwestern University