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Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? - PubMed

  • ️Mon Jan 01 2024

Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not?

Ozge Oztan et al. Mol Autism. 2024.

Abstract

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.

Keywords: Animal model; Arginine vasopressin; Autism spectrum disorder; Cerebrospinal fluid; Dominance rank; Female; Oxytocin; Rhesus macaque; Social functioning; Social responsiveness scale.

© 2024. The Author(s).

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Conflict of interest statement

The Board of Trustees of the Leland Stanford Junior University has filed patent applications related to data reviewed herein: PCT/US2019/019029 (“Methods for diagnosing and determining severity of an autism spectrum disorder”) and PCT/US2019/041250 (“Intranasal Vasopressin Treatment for Social Deficits in Children with Autism”). These patents have not been granted or licensed, and no study author is receiving any financial compensation at this time.

Figures

Fig. 1
Fig. 1

Predictors of mSRS-R score in N = 87 female rhesus macaques. a Non-social behavior frequency did not significantly predict mSRS-R score. b Dominance rank significantly predicted mSRS-R score, with higher ranking individuals having lower autistic-like trait burden. The least-squares-line is plotted. The mSRS-R score was corrected for each data point for the other factors in the analysis, equivalent to figuring a Least squares mean (LSM) and SE for a categorical variable. Then, for ease of visualization, the data were binned into eight quantiles, and the mean and SE plotted. The continuous nature of both non-social behavior frequency and mSRS-R scores are visualized

Fig. 2
Fig. 2

Plasma neuropeptide concentration prediction of CSF neuropeptide concentration. a Plasma AVP concentration significantly predicts CSF AVP concentration (n = 14). b In contrast, plasma OXT concentration does not significantly predict CSF OXT concentration (n = 15) in the same animals, using blood plasma and CSF aliquots from the same sample collection. The least-squares-line is plotted. CSF concentration of each neuropeptide was corrected for each data point for the other factors in the analysis, equivalent to figuring a LSM and SE for a categorical variable

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