Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality / A. K. MYERS in Autism Research, 14-7 (July 2021)  

Public ISBD [article]  inAutism Research > 14-7 (July 2021) . - p.1332-1346 Titre : Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality Type de document : Texte imprimé et/ou numérique Auteurs : A. K. MYERS, Auteur ; Catherine F. TALBOT, Auteur ; L. A. DEL ROSSO, Auteur ; A. C. MANESS, Auteur ; S. M. V. SIMMONS, Auteur ; J. P. GARNER, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : p.1332-1346 Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/epidemiology  Autistic Disorder  Humans  Macaca mulatta  Morbidity  Social Behavior  Social Responsiveness Scale  animal model  autism spectrum disorder  medical morbidities  rhesus macaque  social behavior Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1002/aur.2512 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality [Texte imprimé et/ou numérique] / A. K. MYERS, Auteur ; Catherine F. TALBOT, Auteur ; L. A. DEL ROSSO, Auteur ; A. C. MANESS, Auteur ; S. M. V. SIMMONS, Auteur ; J. P. GARNER, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - p.1332-1346. Langues : Anglais (eng) in Autism Research > 14-7 (July 2021) . - p.1332-1346 Mots-clés : Animals  Autism Spectrum Disorder/epidemiology  Autistic Disorder  Humans  Macaca mulatta  Morbidity  Social Behavior  Social Responsiveness Scale  animal model  autism spectrum disorder  medical morbidities  rhesus macaque  social behavior Index. décimale : PER Périodiques Résumé : 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. En ligne : http://dx.doi.org/10.1002/aur.2512 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / O. 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 et/ou numérique Auteurs : O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. 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 et/ou numérique] / O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. 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 / M. 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 et/ou numérique Auteurs : M. G. MARISCAL, Auteur ; O. OZTAN, Auteur ; S. M. ROSE, Auteur ; R. A. LIBOVE, Auteur ; L. P. JACKSON, Auteur ; R. D. SUMIYOSHI, Auteur ; T. H. TRUJILLO, Auteur ; D. S. CARSON, Auteur ; J. M. PHILLIPS, Auteur ; J. P. GARNER, Auteur ; A. 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 et/ou numérique] / M. G. MARISCAL, Auteur ; O. OZTAN, Auteur ; S. M. ROSE, Auteur ; R. A. LIBOVE, Auteur ; L. P. JACKSON, Auteur ; R. D. SUMIYOSHI, Auteur ; T. H. TRUJILLO, Auteur ; D. S. CARSON, Auteur ; J. M. PHILLIPS, Auteur ; J. P. GARNER, Auteur ; A. 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

Plasma anandamide concentrations are lower in children with autism spectrum disorder / Debra S. KARHSON in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 18p. Titre : Plasma anandamide concentrations are lower in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Debra S. KARHSON, Auteur ; K. M. KRASINSKA, Auteur ; J. A. DALLAIRE, Auteur ; R. A. LIBOVE, Auteur ; J. M. PHILLIPS, Auteur ; A. S. CHIEN, Auteur ; J. P. GARNER, Auteur ; A. Y. HARDAN, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 18p. Langues : Anglais (eng) Mots-clés : Anandamide  Autism spectrum disorder  Blood biomarker  Cannabinoid Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112). Findings: Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034). Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0203-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] Plasma anandamide concentrations are lower in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Debra S. KARHSON, Auteur ; K. M. KRASINSKA, Auteur ; J. A. DALLAIRE, Auteur ; R. A. LIBOVE, Auteur ; J. M. PHILLIPS, Auteur ; A. S. CHIEN, Auteur ; J. P. GARNER, Auteur ; A. Y. HARDAN, Auteur ; Karen J. PARKER, Auteur . - 18p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 18p. Mots-clés : Anandamide  Autism spectrum disorder  Blood biomarker  Cannabinoid Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112). Findings: Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034). Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD. En ligne : http://dx.doi.org/10.1186/s13229-018-0203-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

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