Naturally low‐social rhesus macaques exhibit social impairments with direct relevance to autism spectrum disorder (ASD). To more efficiently identify low‐social individuals in a large colony, we exploited, refined, and psychometrically assessed the macaque Social Responsiveness Scale (mSRS), an instrument previously derived from the human ASD screening tool. We performed quantitative social behavior assessments and mSRS ratings on a total of N = 349 rhesus macaques (Macaca mulatta) housed in large, outdoor corrals. In one cohort (N = 116), we conducted inter‐rater and test‐retest reliabilities, and in a second cohort (N = 233), we evaluated the convergent construct and predictive validity of the mSRS‐Revised (mSRS‐R). Only 17 of the original 36 items demonstrated inter‐rater and test–retest reliability, resulting in the 17‐item mSRS‐R. The mSRS‐R showed strong validity: mSRS‐R scores robustly predicted monkeys' social behavior frequencies in home corrals. Monkeys that scored 1.5 standard deviations from the mean on nonsocial behavior likewise exhibited significantly more autistic‐like traits, and mSRS‐R scores predicted individuals' social classification (low‐social vs. high‐social) with 96% accuracy (likelihood ratio chi‐square = 25.07; P < 0.0001). These findings indicate that the mSRS‐R is a reliable, valid, and sensitive measure of social functioning, and like the human SRS, can be used as a high‐throughput screening tool to identify socially impaired individuals in the general population. Lay Summary Variation in autistic traits can be measured in humans using the Social Responsiveness Scale (SRS). Here, we revised this scale for rhesus macaques (i.e., the mSRS‐R), and showed that macaques exhibit individual differences in mSRS‐R scores, and at the behavioral extremes, low‐social vs. high‐social monkeys exhibit more autistic‐like traits. These results suggest that the mSRS‐R can be used as a screening tool to rapidly and accurately identify low‐social monkeys in the general population. Autism Res 2020, 13: 1465–1475. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Most primate species are highly social. Yet, within species, pronounced individual differences in social functioning are evident. In humans, the Social Responsiveness Scale (SRS) measures variation in social functioning. The SRS provides a quantitative measure of social functioning in natural social settings and can be used as a screening tool for autistic traits. The SRS was previously adapted for use in

Background Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1–3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. Methods Cerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: “Case 2A” intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. Results All biological measures (except AKT) showed significant test–retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects). Conclusions These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.

People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether lowsocial monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with welldocumented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. Lay Summary: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model.