Early intervention effective in treating neurodevelopmental disorders

A new study suggests that therapeutic interventions to treat neurodevelopmental disorders may be more effective if delivered during the earliest stages of brain development.

“To stop the progression of neurodevelopmental disorders, it is important to identify how and when brain circuits are changing during development. Our study identifies when circuits are disrupted as well as how brain circuits are corrected,” said the study’s lead author, Molly Huntsman, Ph.D., an associate professor at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, located at the University of Colorado Anschutz Medical Campus.

The study, published in The Journal of Neurosciencediscusses Fragile X Syndrome (FXS), a pervasive neurodevelopmental disorder and a common cause of intellectual disabilityautism and anxiety disorders.

“Currently, there are no approved or effective therapies that target the specific pathophysiology underlying the clinical manifestations of FXS,” said Huntsman. “We hope to provide answers on when and how to treat FXS to help with therapeutic options eventually.”

Researchers at CU Skaggs School of Pharmacy identified possible causal circuit-level changes during a critical period of brain development amenable to therapeutic intervention. They focused on the amygdala, the region of the brain where fear and anxiety are processed.

Using a mouse model of FXS, they identified a critical period of increased circuit plasticity that occurs in early brain development. They showed that fear learning emerges in the brain during these periods of increased plasticity. At the same time, they showed that rapid intervention improves it.

The results suggest that critical period plasticity in the amygdala is increased and can be switched to earlier developmental points. This could cause a “maladaptive” form of plasticity, and yet one that can be treated with therapeutic intervention at key moments in development.

Age at treatment, the study said, is important because early pharmacological intervention proved effective in reducing fear learning in the mouse model.

“This is highly significant and addresses a critical barrier to understanding how circuits are developed in a mouse model of autism and intellectual disability and, more importantly, for treatment options targeted by therapeutic intervention,” Huntsman said.

The researchers said that future clinical trials should focus on critical periods of human development.