Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? / Ozge OZTAN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 8p. Titre : Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? Type de document : Texte imprimé et/ou numérique Auteurs : Ozge OZTAN, Auteur ; Laura A. DEL ROSSO, Auteur ; Sierra M. SIMMONS, Auteur ; Duyen K. K. NGUYEN, Auteur ; Catherine F. TALBOT, Auteur ; John P. CAPITANIO, Auteur ; Joseph P. GARNER, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 8p. Langues : Anglais (eng) Mots-clés : Child  Animals  Humans  Male  Female  Autistic Disorder  Autism Spectrum Disorder  Macaca mulatta  Social Behavior  Arginine Vasopressin/cerebrospinal fluid  Oxytocin  Animal model  Arginine vasopressin  Autism spectrum disorder  Cerebrospinal fluid  Dominance rank  Rhesus macaque  Social functioning  Social responsiveness scale  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. Index. décimale : PER Périodiques Résumé : 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. En ligne : https://dx.doi.org/10.1186/s13229-024-00588-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? [Texte imprimé et/ou numérique] / Ozge OZTAN, Auteur ; Laura A. DEL ROSSO, Auteur ; Sierra M. SIMMONS, Auteur ; Duyen K. K. NGUYEN, Auteur ; Catherine F. TALBOT, Auteur ; John P. CAPITANIO, Auteur ; Joseph P. GARNER, Auteur ; Karen J. PARKER, Auteur . - 8p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 8p. Mots-clés : Child  Animals  Humans  Male  Female  Autistic Disorder  Autism Spectrum Disorder  Macaca mulatta  Social Behavior  Arginine Vasopressin/cerebrospinal fluid  Oxytocin  Animal model  Arginine vasopressin  Autism spectrum disorder  Cerebrospinal fluid  Dominance rank  Rhesus macaque  Social functioning  Social responsiveness scale  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. Index. décimale : PER Périodiques Résumé : 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. En ligne : https://dx.doi.org/10.1186/s13229-024-00588-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism / Catherine F. TALBOT ; Laura A. DEL ROSSO ; Brenda MCCOWAN ; Sreetharan KANTHASWAMY ; David HAIG ; John P. CAPITANIO ; Karen J. PARKER in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 25 p. Titre : Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism Type de document : Texte imprimé et/ou numérique Auteurs : Catherine F. TALBOT, Auteur ; Laura A. DEL ROSSO, Auteur ; Brenda MCCOWAN, Auteur ; Sreetharan KANTHASWAMY, Auteur ; David HAIG, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 25 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N=407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (?(2)(P)) between sons that could uniquely be attributed to their shared genetics (?(2)(g)), expressed as ?(2)(g)/?(2)(P) (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h(2)). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability. En ligne : http://dx.doi.org/10.1186/s13229-023-00556-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism [Texte imprimé et/ou numérique] / Catherine F. TALBOT, Auteur ; Laura A. DEL ROSSO, Auteur ; Brenda MCCOWAN, Auteur ; Sreetharan KANTHASWAMY, Auteur ; David HAIG, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 25 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 25 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N=407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (?(2)(P)) between sons that could uniquely be attributed to their shared genetics (?(2)(g)), expressed as ?(2)(g)/?(2)(P) (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h(2)). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability. En ligne : http://dx.doi.org/10.1186/s13229-023-00556-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

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