Drug target to increase social interaction in autism identified

Researchers have identified a drug target that has the potential to increase social interaction in individuals with some forms of autism spectrum disorder (ASD). Although medications are available for treating symptoms sometimes associated with ASD, such as anxiety, depression, attention-deficit hyperactivity disorder, and irritability, there are no medications currently approved for treatment of the core social interaction deficits that characterise the disorder.

"This research could significantly change our understanding of the causes and brain changes in autism and could lead to new treatment approaches for the harder-to-treat social aspects of ASD," said senior author Edward Brodkin, Associate Professor at Perelman School of Medicine at the University of Pennsylvania in the US. Previous studies on human genetics have implicated a little-studied gene called Protocadherin 10 (PCDH10) in ASD.

The PCDH10 protein is expressed at high levels in particular brain regions, including the amygdala, which mediates emotion and motivation and is implicated in the social deficits of ASD. When one of the two copies of the PCDH10 gene was deleted in mice, these animals showed reduced social approach behaviour, which resembled the social withdrawal of humans with ASD.

This effect was seen more prominently in males than in females, which is consistent with the male predominance of ASD in humans. In addition, these male mice had anomalies in the structure and function of amygdala circuitry, as well as lower levels of certain types of glutamate receptor subunits (called NMDA receptor subunits) in the amygdala.

Social approach deficits in these male mice were rescued by giving them a medication called d-cycloserine, said the study published the journal Biological Psychiatry. "By enhancing NMDA-receptor signaling, the mice went from social avoidance to more typical social approach behaviour," Brodkin said. This finding in the mouse model is also consistent with preliminary clinical studies in humans, the researchers said.