Abstract

Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS) is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS). Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological mechanisms underlying social impairments.

Highlights

  • Autism Spectrum Disorder (ASD) is highly prevalent in the human population, estimated to occur in 1 in 68 individuals in the United States

  • Basic science focused on understanding the biological mechanisms underlying the social impairments associated with ASD and related disorders has been severely hindered by the lack of a robust, translational animal model

  • Several key features of the Macaque Social Responsiveness Scale (mSRS) score distribution were consistent with that found in both humans and chimpanzees on their comparable species-specific tools

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Summary

Introduction

Autism Spectrum Disorder (ASD) is highly prevalent in the human population, estimated to occur in 1 in 68 individuals in the United States (www.cdc.gov). While understanding the basic biological mechanisms underlying ASD is critical for the development of effective treatments, advances have been limited, in part, because the clinical symptomatology of ASD is highly variable, and there is broad genetic heterogeneity across individuals [1,2]. Basic science focused on understanding the biological mechanisms underlying the social impairments associated with ASD and related disorders has been severely hindered by the lack of a robust, translational animal model. Researchers must validate measurement tools for identifying and quantifying the severity of social impairments in the model species that has strong translational relevance for humans. Autism is characterized by social impairments and evaluating whether similar impairments are present in other species can provide unique opportunities to gain insights into the biological mechanisms underlying these behaviors

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