UC San Diego research model outlines autism factors in effort to prevent or reduce it

A new UC San Diego study looks to offer an explanation of how certain genetic predispositions combined with environmental exposures can lead to autism spectrum disorders. Researchers believe their findings might hold the key to reducing or preventing autism cases by as much as half.

The study was published Dec. 9 in the scientific journal Mitochondrion.

The paper outlines a metabolic signaling model that “reframes autism as a treatable disorder of cellular communication and energy metabolism,” according to UC San Diego Health Sciences.

The “three-hit model,” developed from more than a decade of systems biology research, proposes that autism develops when three conditions align: genetic predisposition, or inherited genes that cause mitochondria and cellular signaling pathways to be “unusually sensitive to change”; environmental exposures including infection, immune stress or pollution; and prolonged activation, which occurs when those exposures are extended.

The latter two factors can be reversed, the paper posits. And by detecting them early and intervening to mitigate them, autism risk can be further reduced, the study contends.

Dr. Robert Naviaux, a professor of medicine, pediatrics and pathology at the UCSD School of Medicine and the study’s lead author, estimated that 40-50% of autism cases could be prevented or significantly improved through the processes outlined in the model.

The core of the model is cell danger response, or CDR, which helps cells respond to threats, adapt to changing conditions and heal from injuries and infection. But when stressors or inherited hypersensitivity persists, a breakdown in cellular communication occurs.

As a result, brain circuit formation is interrupted and core features of autism emerge.

“Behavior has a chemical basis,” Naviaux said in a statement. “The CDR regulates that chemistry. When it remains activated too long, it diverts the body’s resources from normal growth and development toward cellular defense, leaving fewer resources for the developing brain.”

The study creates a single biological narrative out of decades of autism-related findings and speaks to the multifaceted nature of autism risk rather than a singular “autism gene.”

Naviaux compared these findings to those of another genetic disorder, phenylketonuria, or PKU, which causes intellectual disabilities if left unaddressed. According to those studies, also based on a three-hit metabolic model, 95% of affected children with a disease-carrying gene were able to develop normally with early detection and intervention.

Navaiaux said several efforts are needed in the future, including refining diagnostic tools, developing drugs that maintain CDR and conducting large, multi-site clinical trials.