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Cerebellum May Be at the Root of Autism

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Posted January 9, 2014

a brainResearchers studying autism spectrum disorders (ASD) are hunting for clues to determine its cause. Autism has traditionally been considered a problem of the cerebral cortex—the part of the brain that influences language use and social interaction. However, recent research suggests the cerebellum may play a primary role in ASD. As more research examines the cerebellum’s functions, it seems increasingly likely that it may be the key to understanding autism. An editorial from the Simons Foundation Autism Research Initiative reviewed findings from four studies that implicate the cerebellum as the prime mover in the autistic brain.

The first study involved abnormalities related to a chromosomal region in the brain, the deletion of which causes Phelan-McDermind syndrome, a disorder characterized by developmental delay and language impairments. The set of genes are also related to autism. Researchers analyzed brain images of ten individuals who had the particular genes deleted. Eight of the group had a smaller-than-normal vermis, which connects the halves of the cerebellum, and an enlarged cavity for the cerebellum. These abnormalities have also been observed in people with autism.

Another study assessed over 3,000 mouse genes, finding two ‘cliques’ of genes, many of which may be related to autism. Both of these gene groups were located in the cerebellum. The researchers had anticipated that the majority of autism candidate genes would be in the cerebral cortex, rather than the cerebellum.

A third study noted the relationship between Purkinje cells (long, branching neurons found in the cerebellum) and autistic brains. Brains of people with ASD have fewer Purkinje cells than normal. Additional research demonstrated that mice lacking a particular gene that causes Purkinje degeneration exhibit autism-like behavior.

Finally, another mice-based study focused on how dopamine is released when the brain lacks Purkinje cells. The researchers studied dopamine pathways in mice that had lost all of their Purkinje cells. The mice’s brains were stimulated to cause a release of dopamine. The mice without Purkinje cells had a lower dopamine release in the prefrontal cortex than the controls.

Some researchers are developing the idea that the cerebellum may be at the root of autism. “Cerebellar dysfunction may be contributing to impaired coordination of social actions in parallel to the ways it contributes to impaired coordination of motor actions,” stated Stewart Mostofsky, director of the Laboratory for Neurocognitive and Imaging Research at Baltimore’s Kennedy Krieger Institute.

This literature review is available via SFARI.org.

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