New drug target to increase social interaction in autism

WASHINGTON:  Scientists have identified a drug target that may increase social interaction in individuals with some forms of autism spectrum disorder.

Although medications are available for treating symptoms associated with autism spectrum disorder (ASD), such as anxiety, depression, attention-deficit hyperactivity disorder, and irritability, there are no medications currently approved for treatment of social interaction deficits in ASD.

“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 Edward S Brodkin, an associate professor at the University of Pennsylvania in the US.

Behavioural symptoms in individuals with autism spectrum disorder have been attributed to aberrant connections between neurons, but the molecular underpinnings of ASD-related behavioural and brain physiology are largely unknown.

Previous studies on human genetics have implicated a gene called Protocadherin 10 (PCDH10) in ASD.

PCDH10 is a neural cell adhesion molecule that is involved in brain development and the maintenance of synapses, the points of connections between neurons where neurotransmitters are released.

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, the 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, which binds to the glycine binding site on the NMDA receptor.

“By enhancing NMDA-receptor signalling, the mice went from social avoidance to more typical social approach behaviour,” Brodkin said.

The finding in the mouse model is also consistent with preliminary clinical studies in humans, researchers said.

D-cycloserine has been shown, in recent small studies, to significantly improve social interactions in older adolescents and young adults with autism spectrum disorders.

The study in mice may give additional impetus to pursue these initial results in human studies with larger-scale clinical studies of d-cycloserine or related medications.

The study was published in the journal Biological Psychiatry. (AGENCIES)


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