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Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms / Y. KATO in Molecular Autism, 12 (2021)
[article]
Titre : Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms Type de document : Texte imprimé et/ou numérique Auteurs : Y. KATO, Auteur ; H. KUWABARA, Auteur ; T. OKADA, Auteur ; T. MUNESUE, Auteur ; S. BENNER, Auteur ; M. KURODA, Auteur ; M. KOJIMA, Auteur ; W. YASSIN, Auteur ; Y. ERIGUCHI, Auteur ; Y. KAMENO, Auteur ; C. MURAYAMA, Auteur ; T. NISHIMURA, Auteur ; K. TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; N. OZAKI, Auteur ; H. KOSAKA, Auteur ; H. YAMASUE, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Administration, Intranasal Adolescent Adult Autistic Disorder/blood/drug therapy/metabolism/psychology Double-Blind Method Facial Expression Humans Male Metabolomics Middle Aged Oxytocin/administration & dosage/blood/pharmacokinetics Sarcosine/analogs & derivatives/blood Social Behavior Treatment Outcome Young Adult Asperger Autism Clinical trial Developmental disorders Facial expression N,N-Dimethylglycine Neuropeptide Oxytocin Plasticity collection, management, analysis, and interpretation of the data preparation, review, or approval of the manuscript or decision to submit the manuscript for publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N?=?106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P?=?0.043, d?=?0.74, N?=?83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR)?=?0.004, d?=?1.13, N?=?60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR)?=?0.006, r?=?-?0.485, N?=?43) and deteriorations between 2 and 4 weeks (P(FDR)?=?0.032, r?=?0.415, N?=?37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 15 p.[article] Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms [Texte imprimé et/ou numérique] / Y. KATO, Auteur ; H. KUWABARA, Auteur ; T. OKADA, Auteur ; T. MUNESUE, Auteur ; S. BENNER, Auteur ; M. KURODA, Auteur ; M. KOJIMA, Auteur ; W. YASSIN, Auteur ; Y. ERIGUCHI, Auteur ; Y. KAMENO, Auteur ; C. MURAYAMA, Auteur ; T. NISHIMURA, Auteur ; K. TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; N. OZAKI, Auteur ; H. KOSAKA, Auteur ; H. YAMASUE, Auteur . - 15 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 15 p.
Mots-clés : Administration, Intranasal Adolescent Adult Autistic Disorder/blood/drug therapy/metabolism/psychology Double-Blind Method Facial Expression Humans Male Metabolomics Middle Aged Oxytocin/administration & dosage/blood/pharmacokinetics Sarcosine/analogs & derivatives/blood Social Behavior Treatment Outcome Young Adult Asperger Autism Clinical trial Developmental disorders Facial expression N,N-Dimethylglycine Neuropeptide Oxytocin Plasticity collection, management, analysis, and interpretation of the data preparation, review, or approval of the manuscript or decision to submit the manuscript for publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N?=?106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P?=?0.043, d?=?0.74, N?=?83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR)?=?0.004, d?=?1.13, N?=?60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR)?=?0.006, r?=?-?0.485, N?=?43) and deteriorations between 2 and 4 weeks (P(FDR)?=?0.032, r?=?0.415, N?=?37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Beyond the hype and hope: Critical considerations for intranasal oxytocin research in autism spectrum disorder / Gail A. ALVARES in Autism Research, 10-1 (January 2017)
[article]
Titre : Beyond the hype and hope: Critical considerations for intranasal oxytocin research in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Gail A. ALVARES, Auteur ; Daniel S. QUINTANA, Auteur ; Andrew J. O. WHITEHOUSE, Auteur Article en page(s) : p.25-41 Langues : Anglais (eng) Mots-clés : oxytocin neuropeptide hormones nasal spray Index. décimale : PER Périodiques Résumé : Extensive research efforts in the last decade have been expended into understanding whether intranasal oxytocin may be an effective therapeutic in treating social communication impairments in individuals with autism spectrum disorder (ASD). After much hyped early findings, subsequent clinical trials of longer-term administration have yielded more conservative and mixed evidence. However, it is still unclear at this stage whether these more disappointing findings reflect a true null effect or are mitigated by methodological differences masking true effects. In this review, we comprehensively evaluate the rationale for oxytocin as a therapeutic, evaluating evidence from randomized controlled trials, case reports, and open-label studies of oxytocin administration in individuals with ASD. The evidence to date, including reviews of preregistered trials, suggests a number of critical considerations for the design and interpretation of research in this area. These include considering the choice of ASD outcome measures, dosing and nasal spray device issues, and participant selection. Despite these limitations in the field to date, there remains significant potential for oxytocin to ameliorate aspects of the persistent and debilitating social impairments in individuals with ASD. Given the considerable media hype around new treatments for ASD, as well as the needs of eager families, there is an urgent need for researchers to prioritise considering such factors when conducting well-designed and controlled studies to further advance this field. En ligne : http://dx.doi.org/10.1002/aur.1692 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=302
in Autism Research > 10-1 (January 2017) . - p.25-41[article] Beyond the hype and hope: Critical considerations for intranasal oxytocin research in autism spectrum disorder [Texte imprimé et/ou numérique] / Gail A. ALVARES, Auteur ; Daniel S. QUINTANA, Auteur ; Andrew J. O. WHITEHOUSE, Auteur . - p.25-41.
Langues : Anglais (eng)
in Autism Research > 10-1 (January 2017) . - p.25-41
Mots-clés : oxytocin neuropeptide hormones nasal spray Index. décimale : PER Périodiques Résumé : Extensive research efforts in the last decade have been expended into understanding whether intranasal oxytocin may be an effective therapeutic in treating social communication impairments in individuals with autism spectrum disorder (ASD). After much hyped early findings, subsequent clinical trials of longer-term administration have yielded more conservative and mixed evidence. However, it is still unclear at this stage whether these more disappointing findings reflect a true null effect or are mitigated by methodological differences masking true effects. In this review, we comprehensively evaluate the rationale for oxytocin as a therapeutic, evaluating evidence from randomized controlled trials, case reports, and open-label studies of oxytocin administration in individuals with ASD. The evidence to date, including reviews of preregistered trials, suggests a number of critical considerations for the design and interpretation of research in this area. These include considering the choice of ASD outcome measures, dosing and nasal spray device issues, and participant selection. Despite these limitations in the field to date, there remains significant potential for oxytocin to ameliorate aspects of the persistent and debilitating social impairments in individuals with ASD. Given the considerable media hype around new treatments for ASD, as well as the needs of eager families, there is an urgent need for researchers to prioritise considering such factors when conducting well-designed and controlled studies to further advance this field. En ligne : http://dx.doi.org/10.1002/aur.1692 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=302 Predicted role of secretin and oxytocin in the treatment of behavioral and developmental disorders : implications for autism / Martha G. WELCH
Titre : Predicted role of secretin and oxytocin in the treatment of behavioral and developmental disorders : implications for autism Type de document : Texte imprimé et/ou numérique Auteurs : Martha G. WELCH, Auteur ; David A. RUGGIERO, Auteur Année de publication : 2005 Importance : p.273-315 Langues : Anglais (eng) Mots-clés : Secretine Oxytocine Acide ?-aminobutyrique Neuropeptide Index. décimale : SCI-D SCI-D - Neurosciences Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=669 Predicted role of secretin and oxytocin in the treatment of behavioral and developmental disorders : implications for autism [Texte imprimé et/ou numérique] / Martha G. WELCH, Auteur ; David A. RUGGIERO, Auteur . - 2005 . - p.273-315.
Langues : Anglais (eng)
Mots-clés : Secretine Oxytocine Acide ?-aminobutyrique Neuropeptide Index. décimale : SCI-D SCI-D - Neurosciences Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=669 Exemplaires
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