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Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / O. OZTAN in Molecular Autism, 12 (2021)
[article]
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
in Molecular Autism > 12 (2021) . - 50 p.[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 Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development / B. A. CORBETT in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
[article]
Titre : Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development Type de document : Texte imprimé et/ou numérique Auteurs : B. A. CORBETT, Auteur ; Karen L. BALES, Auteur ; D. SWAIN, Auteur ; K. SANDERS, Auteur ; T. A. WEINSTEIN, Auteur ; L. J. MUGLIA, Auteur Article en page(s) : p.32 Langues : Anglais (eng) Mots-clés : Arginine vasopressin Autism Autism spectrum disorder Cortisol Hormone Hydrocortisone LHPA axis Oxytocin Stress Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. METHODS: A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. RESULTS: There was a significant Time x Condition x Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. CONCLUSIONS: For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation. En ligne : http://dx.doi.org/10.1186/s11689-016-9165-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.32[article] Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development [Texte imprimé et/ou numérique] / B. A. CORBETT, Auteur ; Karen L. BALES, Auteur ; D. SWAIN, Auteur ; K. SANDERS, Auteur ; T. A. WEINSTEIN, Auteur ; L. J. MUGLIA, Auteur . - p.32.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.32
Mots-clés : Arginine vasopressin Autism Autism spectrum disorder Cortisol Hormone Hydrocortisone LHPA axis Oxytocin Stress Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. METHODS: A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. RESULTS: There was a significant Time x Condition x Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. CONCLUSIONS: For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation. En ligne : http://dx.doi.org/10.1186/s11689-016-9165-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349