Scientists discover how dozens of genes may contribute to autism

 

  Brain-cell cultures are suspended in a dish at the lab of Sergiu Pasca, a Stanford University professor of psychiatry and behavioral sciences. (Timothy Archibald)

 

Using a host of high-tech tools to simulate brain development in a lab dish, Stanford University researchers have discovered several dozen genes that interfere with crucial steps in the process and may lead to autism, a spectrum of disorders that affects about one in every 36 Americans, impairing their ability to communicate and interact with others.

The results of a decade of work, the findings published in the journal Nature may one day pave the way for scientists to design treatments that allow these phases of brain development to proceed unimpaired.

The study delves into a 20-year-old theory that suggests one cause of autism may be a disruption of the delicate balance between two types of nerve cells found in the brain’s cerebral cortex, the area responsible for higher-level processes such as thought, emotion, decision-making and language.

Some nerve cells in this region of the brain excite other nerve cells, encouraging them to fire; other cells, called interneurons, do the opposite. Too much excitation can impair focus in the brain and cause epilepsy, a seizure disorder that is more common in people with autism than in the general population. Scientists therefore believe a proper balance requires more of the inhibiting interneurons.

 

In the developing fetus, these nerve cells start out deep in the brain in a region called the subpallium, then migrate slowly to the cerebral cortex. The process begins mid-gestation and ends in the infant’s second year of life, said Sergiu Pasca, a Stanford University professor of psychiatry and behavioral sciences who led the study.

                                                                                               

Pasca’s team, which included researchers from the University of California at San Francisco and the Icahn School of Medicine at Mount Sinai, tested 425 genes that have been linked to neurodevelopmental disorders to determine which ones interfere with the generation and migration of interneurons. Genes linked to autism were among those identified in the study.

“What’s really cool about this paper is that autism is a collection of different behaviors, but we don’t have [an] understanding of how those behaviors are connected to differences in the brain,” said James McPartland, a professor of child psychiatry and psychology at the Yale School of Medicine, who was not involved in the study.

The new work advances research into autism by “beginning to create a fundamental understanding of the building blocks of brain development,” he said.