A brain region, called amygdala, is often implicated in the behavior
symptoms of autism spectrum disorder (ASD).
Reducing the function of the autism-associated gene Pcdh10 leads to
impairments in social behavior, revealed a study published in Biological Psychiatry
Reducing Pcdh10 function also disrupted the structure and function of
circuitry in the amygdala.
‘A medication called d-cycloserine helped improve the impaired social behavior in a mouse model of autism spectrum disorder (ASD).’
In the study, first authors Dr. Hannah Schoch and Dr. Arati
Kreibich, both of the University of Pennsylvania, and colleagues found
that neurons in the amygdala of mice lacking one copy of Pcdh10
(Pcdh10+/-) had reduced levels of NMDA glutamate receptor subunits,
indicating disrupted excitatory neural circuitry.
"Our study of Pcdh10+/- mice gives us greater insight into the
biology of social behaviors and into the function of a gene associated
with ASD," said senior author Professor Edward Brodkin, also of the
University of Pennsylvania.
The study also suggests a possible target for treatment of ASD. When
the researchers gave the mice a medication called d-cycloserine, the
impaired social behavior improved. D-cycloserine is an old medication
that was developed as a treatment for tuberculosis. However, nearly 30
years ago, it was discovered that this drug targets the NMDA glutamate
receptor to enhance its function.
Brodkin cautions that although much more work would be necessary in
both animal models and humans to establish the medication as safe and
effective for this use, preliminary clinical studies in humans with ASD
have also shown promise for its use to improve social interactions.
"This study is an example of a principle that we will hold for more psychiatric conditions," said John Krystal, Editor of Biological Psychiatry
"That hypothesis is that when psychiatric syndromes can be targeted to
specific genes, then specific treatments may be implicated."
Reducing the function of the Pcdh10 gene had a more prominent effect
in male mice - female mice did not exhibit the social behavior
deficits seen in males. The finding parallels the male predominance of
ASD in humans, and will be an important line of future research to
understand the genetic underpinnings of sex differences in ASD.