|Cells of the amygdala (red).|
Credit: The lab of Edward Brodkin,
Perelman School of Medicine,
University of Pennsylvania
While there are medications available to treat some of the common symptoms of autism like anxiety, depression, attention deficit hyperactivity disorder (ADHD), and irritability, there is no drug currently approved to address difficulties with social interactions- a defining feature of autism. "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," senior author Edward S. Brodkin, MD, said in a press release.
The research team, which also included Robert T. Schultz, PhD, director of The Center for Autism Research at CHOP and Ted Abel, PhD, the Brush Family Professor of Biology at Penn, found that when one of the two copies of PCDH10 was deleted from the mice, they showed decreased social approach behaviors. The investigators also noted that this habit was observed more often in males than females, which seems consistent with understood behaviors of autism in humans.
Importantly, the researchers were also able to pinpoint the brain circuits that are involved in some of the social difficulties associated with autism. The mice with one deleted PCDH10 gene showed differences in the fine structure of the amygdala, a brain region long thought to play a role in autism.
Next, the researchers treated the affected mice with d-cycloserine, an antibiotic used to treat tuberculosis. The drug is known to boost NMDA glutamate receptor function. "By enhancing NMDA receptor signaling, the mice went from social avoidance to more typical social approach behavior," Brodkin observed.
This finding was in line with the results of preliminary clinical studies of d-cycloserine in human patients with autism, which showed that the drug significantly improved social behaviors in older adolescents and adults diagnosed with autism spectrum disorders. However, these studies in humans are too small and need to be replicated on a larger scale in order to validate the treatment. The researchers say this new data on PCDH10 mutations in mice provides a basis to pursue additional studies in people.
Brodkin and his team plan to continue to study mice to understand why the presence or absence of PCDH10 seems to affect males more than females in terms of social behaviors. They will also continue to study the role the amygdala plays in affecting these behaviors, as a clue to better treatment approaches for social behaviors in certain autism spectrum disorder subtypes.
The findings of the study, “Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene”, were recently published in the journal Biological Psychiatry.
Note: In addition to their primary academic appointments, Dr. Brodkin and Dr. Abel are collaborating faculty members at The Center for Autism Research at CHOP.