Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / Ozge OZTAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 50 p. Titre : Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys Type de document : texte imprimé Auteurs : Ozge OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; Emanuela ARGILLI, Auteur ; Alyssa C. MANESS, Auteur ; Sierra M. SIMMONS, Auteur ; Noreen MOHSIN, Auteur ; Laura A. DEL ROSSO, Auteur ; Joseph P. GARNER, Auteur ; Elliott H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : Arginine vasopressin  Autism spectrum disorder  Biomarker  Cerebrospinal fluid  Kinase signaling pathway  Oxytocin  Rhesus macaque  Social responsiveness scale  Social trait variation  the University of California, San Francisco (UCSF) have filed patent applications  related to biological measures studied herein (Stanford University:  PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism  spectrum disorder”  UCSF: PCT/US2016/014623 “Methods of diagnosing and treating  autism spectrum disorders”). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. EHS serves on the  advisory board for Retrophin Inc. All other authors declare that they have no  competing interests. Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys [texte imprimé] / Ozge OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; Emanuela ARGILLI, Auteur ; Alyssa C. MANESS, Auteur ; Sierra M. SIMMONS, Auteur ; Noreen MOHSIN, Auteur ; Laura A. DEL ROSSO, Auteur ; Joseph P. GARNER, Auteur ; Elliott H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 50 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 50 p. Mots-clés : Arginine vasopressin  Autism spectrum disorder  Biomarker  Cerebrospinal fluid  Kinase signaling pathway  Oxytocin  Rhesus macaque  Social responsiveness scale  Social trait variation  the University of California, San Francisco (UCSF) have filed patent applications  related to biological measures studied herein (Stanford University:  PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism  spectrum disorder”  UCSF: PCT/US2016/014623 “Methods of diagnosing and treating  autism spectrum disorders”). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. EHS serves on the  advisory board for Retrophin Inc. All other authors declare that they have no  competing interests. Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Blood oxytocin concentration positively predicts contagious yawning behavior in children with autism spectrum disorder / Michael G. MARISCAL in Autism Research, 12-8 (August 2019)  

Public ISBD [article]  inAutism Research > 12-8 (August 2019) . - p.1156-1161 Titre : Blood oxytocin concentration positively predicts contagious yawning behavior in children with autism spectrum disorder Type de document : texte imprimé Auteurs : Michael G. MARISCAL, Auteur ; Ozge OZTAN, Auteur ; Sophie M. ROSE, Auteur ; Robin A. LIBOVE, Auteur ; Lisa P. JACKSON, Auteur ; Raena D. SUMIYOSHI, Auteur ; Tara H. TRUJILLO, Auteur ; Dean S. CARSON, Auteur ; Jennifer M. PHILLIPS, Auteur ; Joseph P. GARNER, Auteur ; Antonio Y. HARDAN, Auteur ; Karen J. PARKER, Auteur Article en page(s) : p.1156-1161 Langues : Anglais (eng) Mots-clés : autism  contagion  empathy  oxytocin  social functioning  yawning Index. décimale : PER Périodiques Résumé : Research suggests that children with autism spectrum disorder (ASD) may have reduced empathy, as measured by an impaired contagious yawn response, compared to typically developing (TD) children. Other research has failed to replicate this finding, instead attributing this phenomenon to group differences in attention paid to yawn stimuli. A third possibility is that only a subgroup of children with ASD exhibits the impaired contagious yawn response, and that it can be identified biologically. Here we quantified blood concentrations of the "social" neuropeptide oxytocin (OXT) and evaluated yawning behavior and attention rates during a laboratory task in children with ASD (N = 34) and TD children (N = 30) aged 6-12 years. No group difference in contagious yawning behavior was found. However, a blood OXT concentration x group (ASD vs. TD) interaction positively predicted contagious yawning behavior (F1,50 = 7.4987; P = 0.0085). Specifically, blood OXT concentration was positively related to contagious yawning behavior in children with ASD, but not in TD children. This finding was not due to delayed perception of yawn stimuli and was observed whether attention paid to test stimuli and clinical symptom severity were included in the analysis or not. These findings suggest that only a biologically defined subset of children with ASD exhibits reduced empathy, as measured by the impaired contagious yawn response, and that prior conflicting reports of this behavioral phenomenon may be attributable, at least in part, to variable mean OXT concentrations across different ASD study cohorts. Autism Res 2019, 12: 1156-1161. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism may contagiously yawn (i.e., yawn in response to another's yawn) less often than people without autism. We find that people with autism who have lower levels of blood oxytocin (OXT), a hormone involved in social behavior and empathy, show decreased contagious yawning, but those who have higher blood OXT levels do not differ in contagious yawning from controls. This suggests that decreased contagious yawning may only occur in a biologically defined subset of people with autism. En ligne : http://dx.doi.org/10.1002/aur.2135 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405 [article] Blood oxytocin concentration positively predicts contagious yawning behavior in children with autism spectrum disorder [texte imprimé] / Michael G. MARISCAL, Auteur ; Ozge OZTAN, Auteur ; Sophie M. ROSE, Auteur ; Robin A. LIBOVE, Auteur ; Lisa P. JACKSON, Auteur ; Raena D. SUMIYOSHI, Auteur ; Tara H. TRUJILLO, Auteur ; Dean S. CARSON, Auteur ; Jennifer M. PHILLIPS, Auteur ; Joseph P. GARNER, Auteur ; Antonio Y. HARDAN, Auteur ; Karen J. PARKER, Auteur . - p.1156-1161. Langues : Anglais (eng) in Autism Research > 12-8 (August 2019) . - p.1156-1161 Mots-clés : autism  contagion  empathy  oxytocin  social functioning  yawning Index. décimale : PER Périodiques Résumé : Research suggests that children with autism spectrum disorder (ASD) may have reduced empathy, as measured by an impaired contagious yawn response, compared to typically developing (TD) children. Other research has failed to replicate this finding, instead attributing this phenomenon to group differences in attention paid to yawn stimuli. A third possibility is that only a subgroup of children with ASD exhibits the impaired contagious yawn response, and that it can be identified biologically. Here we quantified blood concentrations of the "social" neuropeptide oxytocin (OXT) and evaluated yawning behavior and attention rates during a laboratory task in children with ASD (N = 34) and TD children (N = 30) aged 6-12 years. No group difference in contagious yawning behavior was found. However, a blood OXT concentration x group (ASD vs. TD) interaction positively predicted contagious yawning behavior (F1,50 = 7.4987; P = 0.0085). Specifically, blood OXT concentration was positively related to contagious yawning behavior in children with ASD, but not in TD children. This finding was not due to delayed perception of yawn stimuli and was observed whether attention paid to test stimuli and clinical symptom severity were included in the analysis or not. These findings suggest that only a biologically defined subset of children with ASD exhibits reduced empathy, as measured by the impaired contagious yawn response, and that prior conflicting reports of this behavioral phenomenon may be attributable, at least in part, to variable mean OXT concentrations across different ASD study cohorts. Autism Res 2019, 12: 1156-1161. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism may contagiously yawn (i.e., yawn in response to another's yawn) less often than people without autism. We find that people with autism who have lower levels of blood oxytocin (OXT), a hormone involved in social behavior and empathy, show decreased contagious yawning, but those who have higher blood OXT levels do not differ in contagious yawning from controls. This suggests that decreased contagious yawning may only occur in a biologically defined subset of people with autism. En ligne : http://dx.doi.org/10.1002/aur.2135 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405

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 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] / 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

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