- Awarded: 2019
- Award Type: Director
- Award #: 627146
Karen Parker’s team has used the extremes of naturally occurring variation in the social behavior of rhesus monkeys to develop a novel model of social deficits with direct relevance to autism spectrum disorder (ASD). Specifically, adult low-social (LS) monkeys initiate fewer affiliative interactions, exhibit greater social information processing abnormalities, and show a greater burden of autism-related traits compared to high-social (HS) monkeys1-3.
Evidence also suggests that the arginine vasopressin (AVP) signaling pathway plays a critical role in regulating social abilities that are changed in ASD. For example, in studies supported in part by a SFARI Pilot Award and a Research Award, Parker and her colleagues found that adult LS monkeys have lower cerebrospinal fluid (CSF) AVP concentrations compared to HS monkeys. Importantly, these findings translated to children with ASD and human neonates who subsequently received an ASD diagnosis4,5. Both LS monkeys and ASD children with the lowest CSF AVP concentrations exhibited the greatest social challenges severity.
Although this evidence is compelling, successful ASD interventions will need to manipulate specific pathways at an early age in order to alter developmental trajectories while the brain still retains much of its plasticity. With an eye towards identifying (and ultimately treating) “at-risk” young monkeys, Parker’s team has found behavioral markers in infancy that predict with high accuracy poor social outcomes in adulthood6.
A goal of this project therefore is to test whether the CSF AVP deficit that was previously identified in adult LS monkeys exists in “at-risk” infant monkeys, and whether these infants exhibit poor social cognition abilities in other domains relevant to ASD. Parker and her team plan to identify infant monkeys at the extremes of face recognition ability (a key behavioral marker that predicts adult social challenges). These infants will then undergo CSF collection and additional social processing and social attention assessments.
The researchers hypothesize that infant monkeys with face recognition difficulties will have lower CSF AVP concentrations and perform more poorly on social cognition tests. If Parker’s predictions are correct, she will be poised to initiate a CSF AVP-stratified pharmacological intervention to improve social outcomes in “at-risk” young monkeys.
- Capitanio J.P. Primates 43, 169-177 (2002) PubMed
- Parker K.J. et al. Transl. Med. 10, eaam9100 (2018) PubMed
- Talbot C.F. et al. Autism Res. 13, 1465- 1475 (2020) PubMed
- Otzan O. et al. Ann Neurol. 84, 611-615 (2018) PubMed
- Otzan O. et al. Proc. Natl. Acad. Sci. USA 117, 10609-10613 (2020) PubMed
- Sclafani V. et al. PLoS One 11, e0165401 (2016) PubMed