Can repeated intranasal oxytocin administration affect reduced neural sensitivity towards expressive faces in autism? A randomized controlled trial / Matthijs MOERKERKE in Journal of Child Psychology and Psychiatry, 64-11 (November 2023)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 64-11 (November 2023) . - p.1583-1595 Titre : Can repeated intranasal oxytocin administration affect reduced neural sensitivity towards expressive faces in autism? A randomized controlled trial Type de document : Texte imprimé et/ou numérique Auteurs : Matthijs MOERKERKE, Auteur ; Nicky DANIELS, Auteur ; Stephanie VAN DER DONCK, Auteur ; Laura TIBERMONT, Auteur ; Tiffany TANG, Auteur ; Edward DEBBAUT, Auteur ; Annelies BAMPS, Auteur ; Jellina PRINSEN, Auteur ; Jean STEYAERT, Auteur ; Kaat ALAERTS, Auteur ; Bart BOETS, Auteur Article en page(s) : p.1583-1595 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication and interaction. Crucial for efficient social interaction is the ability to quickly and accurately extract information from a person's face. Frequency-tagging electroencephalography (EEG) is a novel tool to quantify face-processing sensitivity in a robust and implicit manner. In terms of intervention approaches, intranasal administration of oxytocin (OT) is increasingly considered as a potential pharmacological approach for improving socio-communicative difficulties in ASD, through enhancing social salience and/or reducing (social) stress and anxiety. Methods In this randomized, double-blind, placebo-controlled, mechanistic pharmaco-neuroimaging clinical trial, we implemented frequency-tagging EEG to conduct an exploratory investigation into the impact of repeated OT administration (4?weeks, 12?IU, twice daily) on neural sensitivity towards happy and fearful facial expressions in children with ASD (8-12?years old; OT: n=29; placebo: n=32). Neural effects were assessed at baseline, post-nasal spray (24?hr after the last nasal spray) and at a follow-up session, 4?weeks after the OT administration period. At baseline, neural assessments of children with ASD were compared with those of an age- and gender-matched cohort of neurotypical (NT) children (n=39). Results Children with ASD demonstrated reduced neural sensitivity towards expressive faces, as compared to NT children. Upon nasal spray administration, children with ASD displayed a significant increase in neural sensitivity at the post- and follow-up sessions, but only in the placebo group, likely reflecting an implicit learning effect. Strikingly, in the OT group, neural sensitivity remained unaffected from the baseline to the post-session, likely reflecting a dampening of an otherwise typically occurring implicit learning effect. Conclusions First, we validated the robustness of the frequency-tagging EEG approach to assess reduced neural sensitivity towards expressive faces in children with ASD. Furthermore, in contrast to social salience effects observed after single-dose administrations, repeated OT administration dampened typically occurring learning effects in neural sensitivity. In line with OT's social anxiolytic account, these observations possibly reflect a predominant (social) stress regulatory effect towards emotionally evocative faces after repeated OT administration. En ligne : https://doi.org/10.1111/jcpp.13850 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=512 [article] Can repeated intranasal oxytocin administration affect reduced neural sensitivity towards expressive faces in autism? A randomized controlled trial [Texte imprimé et/ou numérique] / Matthijs MOERKERKE, Auteur ; Nicky DANIELS, Auteur ; Stephanie VAN DER DONCK, Auteur ; Laura TIBERMONT, Auteur ; Tiffany TANG, Auteur ; Edward DEBBAUT, Auteur ; Annelies BAMPS, Auteur ; Jellina PRINSEN, Auteur ; Jean STEYAERT, Auteur ; Kaat ALAERTS, Auteur ; Bart BOETS, Auteur . - p.1583-1595. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 64-11 (November 2023) . - p.1583-1595 Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication and interaction. Crucial for efficient social interaction is the ability to quickly and accurately extract information from a person's face. Frequency-tagging electroencephalography (EEG) is a novel tool to quantify face-processing sensitivity in a robust and implicit manner. In terms of intervention approaches, intranasal administration of oxytocin (OT) is increasingly considered as a potential pharmacological approach for improving socio-communicative difficulties in ASD, through enhancing social salience and/or reducing (social) stress and anxiety. Methods In this randomized, double-blind, placebo-controlled, mechanistic pharmaco-neuroimaging clinical trial, we implemented frequency-tagging EEG to conduct an exploratory investigation into the impact of repeated OT administration (4?weeks, 12?IU, twice daily) on neural sensitivity towards happy and fearful facial expressions in children with ASD (8-12?years old; OT: n=29; placebo: n=32). Neural effects were assessed at baseline, post-nasal spray (24?hr after the last nasal spray) and at a follow-up session, 4?weeks after the OT administration period. At baseline, neural assessments of children with ASD were compared with those of an age- and gender-matched cohort of neurotypical (NT) children (n=39). Results Children with ASD demonstrated reduced neural sensitivity towards expressive faces, as compared to NT children. Upon nasal spray administration, children with ASD displayed a significant increase in neural sensitivity at the post- and follow-up sessions, but only in the placebo group, likely reflecting an implicit learning effect. Strikingly, in the OT group, neural sensitivity remained unaffected from the baseline to the post-session, likely reflecting a dampening of an otherwise typically occurring implicit learning effect. Conclusions First, we validated the robustness of the frequency-tagging EEG approach to assess reduced neural sensitivity towards expressive faces in children with ASD. Furthermore, in contrast to social salience effects observed after single-dose administrations, repeated OT administration dampened typically occurring learning effects in neural sensitivity. In line with OT's social anxiolytic account, these observations possibly reflect a predominant (social) stress regulatory effect towards emotionally evocative faces after repeated OT administration. En ligne : https://doi.org/10.1111/jcpp.13850 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=512

Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT / Matthijs MOERKERKE ; Nicky DANIELS ; Qianqian ZHANG ; Ricchiuti GRAZIA ; Jean STEYAERT ; Jellina PRINSEN ; Bart BOETS in Journal of Child Psychology and Psychiatry, 65-10 (October 2024)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 65-10 (October 2024) . - p.1311-1326 Titre : Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT Type de document : Texte imprimé et/ou numérique Auteurs : Matthijs MOERKERKE, Auteur ; Nicky DANIELS, Auteur ; Qianqian ZHANG, Auteur ; Ricchiuti GRAZIA, Auteur ; Jean STEYAERT, Auteur ; Jellina PRINSEN, Auteur ; Bart BOETS, Auteur Article en page(s) : p.1311-1326 Langues : Anglais (eng) Mots-clés : Oxytocin  autism spectrum disorder  electroencephalography  heart rate variability  neural rhythms  alpha  theta  signal to noise Index. décimale : PER Périodiques Résumé : Background Shifts in peak frequencies of oscillatory neural rhythms are put forward as a principal mechanism by which cross-frequency coupling/decoupling is implemented in the brain. During active neural processing, functional integration is facilitated through transitory formations of ?harmonic? cross-frequency couplings, whereas ?nonharmonic? decoupling among neural oscillatory rhythms is postulated to characterize the resting, default state of the brain, minimizing the occurrence of spurious, noisy, background couplings. Methods Within this exploratory, randomized, placebo-controlled trial, we assessed whether the transient occurrence of nonharmonic and harmonic relationships between peak-frequencies in the alpha (8?14?Hz) and theta (4?8?Hz) bands is impacted by intranasal administration of oxytocin, a neuromodulator implicated in improving homeostasis and reducing stress/anxiety. To do so, resting-state electroencephalography was acquired before and after 4?weeks of oxytocin administration (12?IU twice-daily) in children with autism spectrum disorder (8?12?years, n?=?33 oxytocin; n?=?34 placebo). At the baseline, neural assessments of children with autism were compared with those of a matched cohort of children without autism (n?=?40). Results Compared to nonautistic peers, autistic children displayed a lower incidence of nonharmonic alpha-theta cross-frequency decoupling, indicating a higher incidence of spurious ?noisy? coupling in their resting brain (p?=?.001). Dimensionally, increased neural coupling was associated with more social difficulties (p?=?.002) and lower activity of the parasympathetic ?rest & digest? branch of the autonomic nervous system (p?=?.018), indexed with high-frequency heart-rate-variability. Notably, after oxytocin administration, the transient formation of nonharmonic cross-frequency configurations was increased in the cohort of autistic children (p? En ligne : https://doi.org/10.1111/jcpp.13966 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=535 [article] Chronic oxytocin improves neural decoupling at rest in children with autism: an exploratory RCT [Texte imprimé et/ou numérique] / Matthijs MOERKERKE, Auteur ; Nicky DANIELS, Auteur ; Qianqian ZHANG, Auteur ; Ricchiuti GRAZIA, Auteur ; Jean STEYAERT, Auteur ; Jellina PRINSEN, Auteur ; Bart BOETS, Auteur . - p.1311-1326. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 65-10 (October 2024) . - p.1311-1326 Mots-clés : Oxytocin  autism spectrum disorder  electroencephalography  heart rate variability  neural rhythms  alpha  theta  signal to noise Index. décimale : PER Périodiques Résumé : Background Shifts in peak frequencies of oscillatory neural rhythms are put forward as a principal mechanism by which cross-frequency coupling/decoupling is implemented in the brain. During active neural processing, functional integration is facilitated through transitory formations of ?harmonic? cross-frequency couplings, whereas ?nonharmonic? decoupling among neural oscillatory rhythms is postulated to characterize the resting, default state of the brain, minimizing the occurrence of spurious, noisy, background couplings. Methods Within this exploratory, randomized, placebo-controlled trial, we assessed whether the transient occurrence of nonharmonic and harmonic relationships between peak-frequencies in the alpha (8?14?Hz) and theta (4?8?Hz) bands is impacted by intranasal administration of oxytocin, a neuromodulator implicated in improving homeostasis and reducing stress/anxiety. To do so, resting-state electroencephalography was acquired before and after 4?weeks of oxytocin administration (12?IU twice-daily) in children with autism spectrum disorder (8?12?years, n?=?33 oxytocin; n?=?34 placebo). At the baseline, neural assessments of children with autism were compared with those of a matched cohort of children without autism (n?=?40). Results Compared to nonautistic peers, autistic children displayed a lower incidence of nonharmonic alpha-theta cross-frequency decoupling, indicating a higher incidence of spurious ?noisy? coupling in their resting brain (p?=?.001). Dimensionally, increased neural coupling was associated with more social difficulties (p?=?.002) and lower activity of the parasympathetic ?rest & digest? branch of the autonomic nervous system (p?=?.018), indexed with high-frequency heart-rate-variability. Notably, after oxytocin administration, the transient formation of nonharmonic cross-frequency configurations was increased in the cohort of autistic children (p? En ligne : https://doi.org/10.1111/jcpp.13966 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=535

Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial / Matthijs MOERKERKE ; Jean STEYAERT ; Annelies BAMPS ; Edward DEBBAUT ; Jellina PRINSEN ; Tiffany TANG ; Stephanie VAN DER DONCK ; Bart BOETS ; Kaat ALAERTS in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 16 p. Titre : Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial Type de document : Texte imprimé et/ou numérique Auteurs : Matthijs MOERKERKE, Auteur ; Jean STEYAERT, Auteur ; Annelies BAMPS, Auteur ; Edward DEBBAUT, Auteur ; Jellina PRINSEN, Auteur ; Tiffany TANG, Auteur ; Stephanie VAN DER DONCK, Auteur ; Bart BOETS, Auteur ; Kaat ALAERTS, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established. METHODS: A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8-12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin. RESULTS: In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness. LIMITATIONS: Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities. CONCLUSIONS: Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors. Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE ). En ligne : http://dx.doi.org/10.1186/s13229-023-00546-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial [Texte imprimé et/ou numérique] / Matthijs MOERKERKE, Auteur ; Jean STEYAERT, Auteur ; Annelies BAMPS, Auteur ; Edward DEBBAUT, Auteur ; Jellina PRINSEN, Auteur ; Tiffany TANG, Auteur ; Stephanie VAN DER DONCK, Auteur ; Bart BOETS, Auteur ; Kaat ALAERTS, Auteur . - 16 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 16 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established. METHODS: A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8-12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin. RESULTS: In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness. LIMITATIONS: Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities. CONCLUSIONS: Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors. Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE ). En ligne : http://dx.doi.org/10.1186/s13229-023-00546-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Oxytocin receptor gene (OXTR) DNA methylation is associated with autism and related social traits – A systematic review / Matthijs MOERKERKE in Research in Autism Spectrum Disorders, 85 (July 2021)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 85 (July 2021) . - 101785 Titre : Oxytocin receptor gene (OXTR) DNA methylation is associated with autism and related social traits – A systematic review Type de document : Texte imprimé et/ou numérique Auteurs : Matthijs MOERKERKE, Auteur ; Marie-Laure BONTE, Auteur ; Nicky DANIELS, Auteur ; Viktoria CHUBAR, Auteur ; Kaat ALAERTS, Auteur ; Jean STEYAERT, Auteur ; Bart BOETS, Auteur Article en page(s) : 101785 Langues : Anglais (eng) Mots-clés : Oxytocin receptor gene  Epigenetics  DNA methylation  Autism  Social behaviour Index. décimale : PER Périodiques Résumé : There is emerging evidence implicating oxytocin receptor gene (OXTR) DNA methylation (DNAm) in social behaviour. This review investigated its association with autism spectrum disorder (ASD) characteristics and related social dimensions, both in individuals with and without ASD. Twelve articles investigating OXTR DNAm in relation to ASD, social perception/cognition and social anxiety were included. We found that hypermethylation is associated with (i) higher quantitative autism traits in adults, reflecting a higher incidence of autism characteristics, (ii) increased brain activity while performing social tasks (indicating a higher need for resources) and (iii) decreased functional connectivity. (iv) Contradictory, hypomethylation was found to be present in children (especially boys) with ASD and was also associated with more social anxiety. While the included studies displayed a large variability, for example in terms of population characteristics, analysed OXTR DNAm regions, and adopted scales/questionnaires, an initial developmental pattern of results emerged, suggesting an association between hypermethylation of OXTR and autism traits in adults. Nonetheless, future studies are warranted to corroborate these initial conclusions. En ligne : https://doi.org/10.1016/j.rasd.2021.101785 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=458 [article] Oxytocin receptor gene (OXTR) DNA methylation is associated with autism and related social traits – A systematic review [Texte imprimé et/ou numérique] / Matthijs MOERKERKE, Auteur ; Marie-Laure BONTE, Auteur ; Nicky DANIELS, Auteur ; Viktoria CHUBAR, Auteur ; Kaat ALAERTS, Auteur ; Jean STEYAERT, Auteur ; Bart BOETS, Auteur . - 101785. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 85 (July 2021) . - 101785 Mots-clés : Oxytocin receptor gene  Epigenetics  DNA methylation  Autism  Social behaviour Index. décimale : PER Périodiques Résumé : There is emerging evidence implicating oxytocin receptor gene (OXTR) DNA methylation (DNAm) in social behaviour. This review investigated its association with autism spectrum disorder (ASD) characteristics and related social dimensions, both in individuals with and without ASD. Twelve articles investigating OXTR DNAm in relation to ASD, social perception/cognition and social anxiety were included. We found that hypermethylation is associated with (i) higher quantitative autism traits in adults, reflecting a higher incidence of autism characteristics, (ii) increased brain activity while performing social tasks (indicating a higher need for resources) and (iii) decreased functional connectivity. (iv) Contradictory, hypomethylation was found to be present in children (especially boys) with ASD and was also associated with more social anxiety. While the included studies displayed a large variability, for example in terms of population characteristics, analysed OXTR DNAm regions, and adopted scales/questionnaires, an initial developmental pattern of results emerged, suggesting an association between hypermethylation of OXTR and autism traits in adults. Nonetheless, future studies are warranted to corroborate these initial conclusions. En ligne : https://doi.org/10.1016/j.rasd.2021.101785 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=458

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