Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder / Stephen K. SIECINSKI in Autism Research, 16-3 (March 2023)  

Public ISBD [article]  inAutism Research > 16-3 (March 2023) . - p.502-523 Titre : Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder Type de document : texte imprimé Auteurs : Stephen K. SIECINSKI, Auteur ; Stephanie N. GIAMBERARDINO, Auteur ; Marina SPANOS, Auteur ; Annalise C. HAUSER, Auteur ; Jason R. GIBSON, Auteur ; Tara CHANDRASEKHAR, Auteur ; Maria Del Pilar TRELLES, Auteur ; Carol M. ROCKHILL, Auteur ; Michelle L. PALUMBO, Auteur ; Allyson Witters CUNDIFF, Auteur ; Alicia MONTGOMERY, Auteur ; Paige SIPER, Auteur ; Mendy B. MINJAREZ, Auteur ; Lisa A. NOWINSKI, Auteur ; Sarah MARLER, Auteur ; Lydia C. KWEE, Auteur ; Lauren C. SHUFFREY, Auteur ; Cheryl ALDERMAN, Auteur ; Jordana WEISSMAN, Auteur ; Brooke ZAPPONE, Auteur ; Jennifer E. MULLETT, Auteur ; Hope CROSSON, Auteur ; Natalie HONG, Auteur ; Sheng LUO, Auteur ; Lilin SHE, Auteur ; Manjushri BHAPKAR, Auteur ; Russell DEAN, Auteur ; Abby SCHEER, Auteur ; Jacqueline L. JOHNSON, Auteur ; Bryan H. KING, Auteur ; Christopher J. MCDOUGLE, Auteur ; Kevin B. SANDERS, Auteur ; Soo-Jeong KIM, Auteur ; Alexander KOLEVZON, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur ; Elizabeth R. HAUSER, Auteur ; Linmarie SIKICH, Auteur ; Simon G. GREGORY, Auteur Article en page(s) : p.502-523 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. Lay Summary Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment. En ligne : https://doi.org/10.1002/aur.2884 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=498 [article] Genetic and epigenetic signatures associated with plasma oxytocin levels in children and adolescents with autism spectrum disorder [texte imprimé] / Stephen K. SIECINSKI, Auteur ; Stephanie N. GIAMBERARDINO, Auteur ; Marina SPANOS, Auteur ; Annalise C. HAUSER, Auteur ; Jason R. GIBSON, Auteur ; Tara CHANDRASEKHAR, Auteur ; Maria Del Pilar TRELLES, Auteur ; Carol M. ROCKHILL, Auteur ; Michelle L. PALUMBO, Auteur ; Allyson Witters CUNDIFF, Auteur ; Alicia MONTGOMERY, Auteur ; Paige SIPER, Auteur ; Mendy B. MINJAREZ, Auteur ; Lisa A. NOWINSKI, Auteur ; Sarah MARLER, Auteur ; Lydia C. KWEE, Auteur ; Lauren C. SHUFFREY, Auteur ; Cheryl ALDERMAN, Auteur ; Jordana WEISSMAN, Auteur ; Brooke ZAPPONE, Auteur ; Jennifer E. MULLETT, Auteur ; Hope CROSSON, Auteur ; Natalie HONG, Auteur ; Sheng LUO, Auteur ; Lilin SHE, Auteur ; Manjushri BHAPKAR, Auteur ; Russell DEAN, Auteur ; Abby SCHEER, Auteur ; Jacqueline L. JOHNSON, Auteur ; Bryan H. KING, Auteur ; Christopher J. MCDOUGLE, Auteur ; Kevin B. SANDERS, Auteur ; Soo-Jeong KIM, Auteur ; Alexander KOLEVZON, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur ; Elizabeth R. HAUSER, Auteur ; Linmarie SIKICH, Auteur ; Simon G. GREGORY, Auteur . - p.502-523. Langues : Anglais (eng) in Autism Research > 16-3 (March 2023) . - p.502-523 Index. décimale : PER Périodiques Résumé : Abstract Oxytocin (OT), the brain's most abundant neuropeptide, plays an important role in social salience and motivation. Clinical trials of the efficacy of OT in autism spectrum disorder (ASD) have reported mixed results due in part to ASD's complex etiology. We investigated whether genetic and epigenetic variation contribute to variable endogenous OT levels that modulate sensitivity to OT therapy. To carry out this analysis, we integrated genome-wide profiles of DNA-methylation, transcriptional activity, and genetic variation with plasma OT levels in 290 participants with ASD enrolled in a randomized controlled trial of OT. Our analysis identified genetic variants with novel association with plasma OT, several of which reside in known ASD risk genes. We also show subtle but statistically significant association of plasma OT levels with peripheral transcriptional activity and DNA-methylation profiles across several annotated gene sets. These findings broaden our understanding of the effects of the peripheral oxytocin system and provide novel genetic candidates for future studies to decode the complex etiology of ASD and its interaction with OT signaling and OT-based interventions. Lay Summary Oxytocin (OT) is an abundant chemical produced by neurons that plays an important role in social interaction and motivation. We investigated whether genetic and epigenetic factors contribute to variable OT levels in the blood. To this, we integrated genetic, gene expression, and non-DNA regulated (epigenetic) signatures with blood OT levels in 290 participants with autism enrolled in an OT clinical trial. We identified genetic association with plasma OT, several of which reside in known autism risk genes. We also show statistically significant association of plasma OT levels with gene expression and epigenetic across several gene pathways. These findings broaden our understanding of the factors that influence OT levels in the blood for future studies to decode the complex presentation of autism and its interaction with OT and OT-based treatment. En ligne : https://doi.org/10.1002/aur.2884 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=498

The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder / Rachel K. GREENE in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 12 p. Titre : The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder Type de document : texte imprimé Auteurs : Rachel K. GREENE, Auteur ; Marina SPANOS, Auteur ; Cheryl ALDERMAN, Auteur ; Edith WALSH, Auteur ; Joshua BIZZELL, Auteur ; Maya G. MOSNER, Auteur ; Jessica L. KINARD, Auteur ; G.D. STUBER, Auteur ; Tara CHANDRASEKHAR, Auteur ; L.C. POLITTE, Auteur ; Linmarie SIKICH, Auteur ; Gabriel S. DICHTER, Auteur Année de publication : 2018 Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Oxytocin  Reward  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. METHODS: In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. RESULTS: Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group x Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. CONCLUSIONS: The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD. En ligne : http://dx.doi.org/10.1186/s11689-018-9228-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder [texte imprimé] / Rachel K. GREENE, Auteur ; Marina SPANOS, Auteur ; Cheryl ALDERMAN, Auteur ; Edith WALSH, Auteur ; Joshua BIZZELL, Auteur ; Maya G. MOSNER, Auteur ; Jessica L. KINARD, Auteur ; G.D. STUBER, Auteur ; Tara CHANDRASEKHAR, Auteur ; L.C. POLITTE, Auteur ; Linmarie SIKICH, Auteur ; Gabriel S. DICHTER, Auteur . - 2018 . - 12 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 12 p. Mots-clés : Autism spectrum disorder  Oxytocin  Reward  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. METHODS: In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. RESULTS: Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group x Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. CONCLUSIONS: The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD. En ligne : http://dx.doi.org/10.1186/s11689-018-9228-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

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