Clock gene mutation found to contribute to the development of autism

Autism spectrum disorder, or ASD, refers to a neurodevelopmental disorder characterized by a wide range of behavioral conditions including challenges with social skills, repetitive behaviors, speech and nonverbal communication. According to the Centers for Disease Control and Prevention, ASD affects one in 44 children in the U.S.

About 50-80% of children with ASD have sleep problems, compared to less than 30% in the general population. The causes of sleep problems in ASD are not entirely clear, but a malfunctioning body clock could be the culprit.

"It has long been recognized that the function of the body clock is frequently disrupted in autism patients and these patients often exhibit various sleep problems," said Ruifeng Cao, MD, PhD, an assistant professor of neuroscience at the U of M Medical School, Duluth Campus and co-author of the study. "But, it is not known whether clock gene disruption can directly cause autism."

The study found that the disruption of an essential clock gene in preclinical models can lead to autistic-like phenotypes. Specifically, the global or cerebellar deletion of the Bmal1 gene can cause severe impairments in sociability, social communication and excessive repetitive behaviors.

The models also illustrated damages to their cerebellum -- or cerebellar ataxia. The research team further studied the pathological changes in the cerebellum and found a number of cellular and molecular changes that indicate neurodevelopmental deficits.

"Clock gene disruption could be a mechanism underlying several forms of autism and potentially other neurodevelopmental conditions, and this finding paves the way for further exciting research," said Christos Gkogkas, PhD, a lab principal investigator in neurobiology at BRI of FORTH.

The research team plans to continue to study other clock genes that are found mutated in ASD. More importantly, they recommend development of novel therapeutic strategies based on their findings.

The study is supported by grants from the National Institute of Health and the Winston and Maxine Wallin Neuroscience Discovery Fund.

The research team consists of Drs. Harry Orr, Alfonso Araque, Paulo Kofuji, and Jonathan Gewirtz (now at Arizona State University) from the U of M Medical School; Dr. Victor Jin from UT Health San Antonio; and Dr. Christos Gkogkas from BRI-FORTH in Greece.