Do Cerebellum Abnormalities Cause Autism?

brainAutism is a complex disorder, with many facets. Scientists don’t know what causes it, but most agree that it has something to do with the brain. Much of the research has focused on the cerebral cortex, the part of the brain responsible for social interaction and language, but recent studies suggest that there may be more to the story.

The cerebellum is the part of the brain that controls motor development and movement. Scientists are discovering that it may also play a part in emotional regulation and attention. William Dobyns, professor of genetic medicine at University of Washington in Seattle, says,

“There’s an emerging body of data that the cerebellum is important for a lot more than regulating your motor movements. It regulates your emotions as well – your affective state – and your attention.”

In a study published last January, Dobyns and his team found that children who carried a deletion of an autism-linked chromosomal region, 22q13, were more likely to have a smaller than normal vermis, which connects the two halves of the cerebellum, an enlarged posterior fassia, the cavity the cerebellum sits within, or both. DNA analysis suggests that two genes in the 22q13 region, PLXNB2 and MAPK8IP2, are most closely linked to abnormalities of the cerebellum.

Another study, published in PLoS Computational Biology in July, suggests that cliques of autism-related genes may affect the cerebellum in mice. The team found a group of 26 autism candidate genes that had a tendency to be expressed together within the cerebellum.

Postmortem studies of autistic brains have consistently shown a reduced number of Purkinje cells, which represent the main output of nerve signals from the cerebellum, with elaborately branching neuronal projections that travel to various regions of the cerebral cortex. Michael Gambello, chief of medical genetics at Emory University School of Medicine in Atlanta, found that mice lacking an autism-related gene, TSC2, in Purkinje cells showed social deficits related to autism. This replicated another study that showed removing a related gene, TSC1, from Purkinje cells also led to autistic behaviors in mice.

Both studies found that the loss of the gene resulted in Purkinje cell degeneration, and that rapamycin, a drug that inhibits a signaling pathway boosted by the two genes, prevents Purkinje cell loss and the development of autism-like behaviors in mice.

Another study by Charles Blaha, director of experimental psychology at the University of Memphis in Tennessee, found that stimulating a part of the cerebellum called the dentate nucleus results in the release of dopamine to the prefrontal cortex.

“Not too many people have paid too much attention to dopamine and its relationship to autism,”

says Blaha, who points out that it is related to several cognitive functions, including theory of mind, learning and memory.

Studies such as these are leading researchers to conclude that the cerebellum plays a bigger role in autism than was previously believed. Gambello says,

“I think that there is very likely a percentage of children out there with autism where the cerebellum is playing a major role.”