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Background: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD., Methods: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models., Results: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found., Limitations: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores., Conclusions: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD., (© 2024. The Author(s).)

Rhesus monkeys and humans are highly social primates, yet both species exhibit pronounced variation in social functioning, spanning a spectrum of sociality. Naturally occurring low sociality in rhesus monkeys may be a promising construct by which to model social impairments relevant to human autism spectrum disorder (ASD), particularly if low sociality is found to be stable across time and associated with diminished social motivation. Thus, to better characterize variation in sociality and social communication profiles, we performed quantitative social behavior assessments on N = 95 male rhesus macaques (Macaca mulatta) housed in large, outdoor groups. In Study 1, we determined the social classification of our subjects by rank-ordering their total frequency of nonsocial behavior. Monkeys with the greatest frequency of nonsocial behavior were classified as low-social (n = 20) and monkeys with the lowest frequency of nonsocial behavior were classified as high-social (n = 21). To assess group differences in social communication profiles, in Study 2, we quantified the rates of transient social communication signals, and whether these social signals were initiated by or directed towards the focal subject. Finally, in Study 3, we assessed the within-individual stability of sociality in a subset of monkeys (n = 11 low-social, n = 11 high-social) two years following our initial observations. Nonsocial behavior frequency significantly correlated across the two timepoints (Studies 1 and 3). Likewise, low-social versus high-social classification accurately predicted classification two years later. Low-social monkeys initiated less prosocial behavior than high-social monkeys, but groups did not differ in receipt of prosocial behavior, nor did they differ in threat behavior. These findings indicate that sociality is a stable, trait-like characteristic and that low sociality is linked to diminished initiation of prosocial behavior in rhesus macaques. This evidence also suggests that low sociality may be a useful construct for gaining mechanistic insight into the social motivational deficits often observed in people with ASD., (© 2022 Wiley Periodicals LLC.)

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 low-social 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 well-documented 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., (© 2021 International Society for Autism Research, Wiley Periodicals LLC.)

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., (© 2020 International Society for Autism Research, Wiley Periodicals, Inc.)