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Low cerebrospinal (CSF) arginine vasopressin (AVP) concentration is a biomarker of social impairment in low-social monkeys and children with autism, suggesting that AVP administration may improve primate social functioning. However, AVP administration also increases aggression, at least in "neurotypical" animals with intact AVP signaling. Here, we tested the effects of a voluntary drug administration method in low-social male rhesus monkeys with high autistic-like trait burden. Monkeys received nebulized AVP or placebo, using a within-subjects design. Study 1 (N = 8) investigated the effects of AVP administration on social cognition in two tests comparing responses to social versus nonsocial stimuli. Test 1: Placebo-administered monkeys lacked face recognition memory, whereas face recognition memory was "rescued" following AVP administration. In contrast, object recognition memory was intact and did not differ between administration conditions. Test 2: Placebo-administered monkeys did not respond to conspecific social communication cues, whereas following AVP administration, they reciprocated affiliative communication cues with species-typical affiliative responses. Importantly, AVP administration did not increase aggressive responses to conspecific aggressive or affiliative overtures. Study 2 (N = 4) evaluated the pharmacokinetics of this administration method. Following AVP nebulization, we observed a linear increase in cisternal CSF AVP levels, and a quadratic rise and fall in blood AVP levels. These findings indicate that nebulized AVP likely penetrates the central nervous system, selectively promotes species-typical responses to social information, and does not induce aggression in low-social individuals. Nebulized AVP therefore may hold promise for managing similar social symptoms in people with autism, particularly in very young or lower functioning individuals., Competing Interests: Competing interests statement:The Board of Trustees of the Leland Stanford Junior University filed a US patent application, 11,951,149 (“Intranasal Vasopressin Treatment for Social Deficits in Children with Autism”). This patent has not been licensed.

When making decisions, humans often strive to uphold objective, absolute standards, such as about what is small versus large, blue versus purple, or unfair versus fair, suggesting that our judgments should not be swayed by extraneous factors such as the sequence or frequency of events to be judged. Yet in previous research, when some items (e.g., threatening faces) became less frequent, humans responded by expanding their concept (of "threatening") to include more ambiguous stimuli. We assessed the origins of this perceptual frequency bias by testing 25 capuchins, seven rhesus monkeys, and 102 humans on a computer task in which they had to classify one circle at a time (pulled from a continuum of 50 circle sizes) as either small or large. Small and large circles initially appeared with equal probability but over time small circles either became less frequent, more frequent, or did not change in frequency. All three species showed changes in judgment, but contrary to predictions, they contracted, rather than expanded, their size judgments of the less frequent category. In other words, when small circles became rare, participants were more likely to judge ambiguous circles sizes as large (and vice versa). This may have been due to the immediate explicit feedback, as has recently been found in humans, and we consider possible mechanisms driving our participants' responses. These results suggest that humans' difficulties in maintaining absolute standards are shared with other animals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.)