A monkey model of naturally occurring social impairments

Autism spectrum disorder (ASD) is characterized by social impairments and is one of the most devastating childhood disorders, but remains poorly understood. Progress has been impeded, in part, by the difficulty of obtaining relevant tissue samples from patients and their matched neurotypical controls. In mouse models, while tissue is available, there is not infrequently discordance between complex human behavior and laboratory-based mouse behavior, even with shared genetic etiologies. These two limitations underscore the tremendous value in developing an animal model of social impairments with more reliable behavioral and biological correlates to the human disease. Rhesus monkeys are an ideal model organism. Like humans, they are highly social, and both species display stable and pronounced individual differences in social functioning. At the behavioral extremes, low-sociable compared to high-sociable male rhesus monkeys initiate fewer affiliative interactions and display more inappropriate social behavior, suggesting both lower social motivation and poorer social skills. Naturally occurring low sociability in male rhesus monkeys therefore presents an exceptional opportunity to study the biology of social impairments. We have recently developed and validated a high-throughput screening tool to rapidly identify naturally occurring low sociability in a large population of captive rhesus monkeys, and have found that cerebrospinal fluid and blood biomarkers implicated in patients with autism are also apparent in low sociable rhesus monkeys. We are currently developing a sophisticated social behavior test battery to better quantify the type and severity of social impairments in low sociable monkeys. Findings from this research program will ultimately link abnormal social behavior with protein and gene based biological changes in a way that has not been previously achievable. We are optimistic that further development of this model will accelerate the discovery of autism biomarkers and novel “drugable” targets, provide new blood-based metrics for treatment response, and streamline the development of effective therapeutics that will benefit patients with presently intractable social impairments.