Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation
Abstract Alterations in the brain’s oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-a...
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Format: | Article |
Language: | English |
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Nature Publishing Group
2023-06-01
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Series: | Translational Psychiatry |
Online Access: | https://doi.org/10.1038/s41398-023-02524-0 |
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author | Margaux Evenepoel Matthijs Moerkerke Nicky Daniels Viktoria Chubar Stephan Claes Jonathan Turner Bart Vanaudenaerde Lynn Willems Johan Verhaeghe Jellina Prinsen Jean Steyaert Bart Boets Kaat Alaerts |
author_facet | Margaux Evenepoel Matthijs Moerkerke Nicky Daniels Viktoria Chubar Stephan Claes Jonathan Turner Bart Vanaudenaerde Lynn Willems Johan Verhaeghe Jellina Prinsen Jean Steyaert Bart Boets Kaat Alaerts |
author_sort | Margaux Evenepoel |
collection | DOAJ |
description | Abstract Alterations in the brain’s oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-aged children with (n = 80) and without (n = 40) ASD (boys/girls 4/1), and also characterizations of DNA methylation (DNAm) of the oxytocin receptor gene (OXTR) were obtained. Further, cortisol levels were assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling. Children with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels at AM were associated with lower stress-induced cortisol at PM, likely reflective of a protective stress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a significant rise in oxytocin levels from the morning to the afternoon was associated with a higher stress-induced cortisol release in the afternoon, likely reflective of a more reactive stress regulatory release of oxytocin for reactively coping with heightened HPA activity. Regarding epigenetic modifications, no overall pattern of OXTR hypo- or hypermethylation was evident in ASD. In control children, a notable association between OXTR methylation and levels of cortisol at PM was evident, likely indicative of a compensatory downregulation of OXTR methylation (higher oxytocin receptor expression) in children with heightened HPA axis activity. Together, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD. |
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id | doaj.art-8f33ae517bb248dead0002f8166fea51 |
institution | Directory Open Access Journal |
issn | 2158-3188 |
language | English |
last_indexed | 2024-03-13T01:52:38Z |
publishDate | 2023-06-01 |
publisher | Nature Publishing Group |
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series | Translational Psychiatry |
spelling | doaj.art-8f33ae517bb248dead0002f8166fea512023-07-02T11:27:26ZengNature Publishing GroupTranslational Psychiatry2158-31882023-06-011311910.1038/s41398-023-02524-0Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylationMargaux Evenepoel0Matthijs Moerkerke1Nicky Daniels2Viktoria Chubar3Stephan Claes4Jonathan Turner5Bart Vanaudenaerde6Lynn Willems7Johan Verhaeghe8Jellina Prinsen9Jean Steyaert10Bart Boets11Kaat Alaerts12KU Leuven, Department of Rehabilitation Sciences, Research Group for NeurorehabilitationKU Leuven, Leuven Autism Research (LAuRes)KU Leuven, Department of Rehabilitation Sciences, Research Group for NeurorehabilitationUniversity Psychiatric Centre, KU LeuvenUniversity Psychiatric Centre, KU LeuvenLuxembourg Institute of Health, Department of Infection and ImmunityKU Leuven, Department of Chronic Illness and Metabolism, Laboratory of Respiratory Diseases and Thoracic SurgeryKU Leuven, Department of Chronic Illness and Metabolism, Laboratory of Respiratory Diseases and Thoracic SurgeryKU Leuven, Department of Development and Regeneration, Research Group Woman and ChildKU Leuven, Department of Rehabilitation Sciences, Research Group for NeurorehabilitationKU Leuven, Leuven Autism Research (LAuRes)KU Leuven, Leuven Autism Research (LAuRes)KU Leuven, Department of Rehabilitation Sciences, Research Group for NeurorehabilitationAbstract Alterations in the brain’s oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-aged children with (n = 80) and without (n = 40) ASD (boys/girls 4/1), and also characterizations of DNA methylation (DNAm) of the oxytocin receptor gene (OXTR) were obtained. Further, cortisol levels were assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling. Children with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels at AM were associated with lower stress-induced cortisol at PM, likely reflective of a protective stress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a significant rise in oxytocin levels from the morning to the afternoon was associated with a higher stress-induced cortisol release in the afternoon, likely reflective of a more reactive stress regulatory release of oxytocin for reactively coping with heightened HPA activity. Regarding epigenetic modifications, no overall pattern of OXTR hypo- or hypermethylation was evident in ASD. In control children, a notable association between OXTR methylation and levels of cortisol at PM was evident, likely indicative of a compensatory downregulation of OXTR methylation (higher oxytocin receptor expression) in children with heightened HPA axis activity. Together, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD.https://doi.org/10.1038/s41398-023-02524-0 |
spellingShingle | Margaux Evenepoel Matthijs Moerkerke Nicky Daniels Viktoria Chubar Stephan Claes Jonathan Turner Bart Vanaudenaerde Lynn Willems Johan Verhaeghe Jellina Prinsen Jean Steyaert Bart Boets Kaat Alaerts Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation Translational Psychiatry |
title | Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation |
title_full | Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation |
title_fullStr | Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation |
title_full_unstemmed | Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation |
title_short | Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation |
title_sort | endogenous oxytocin levels in children with autism associations with cortisol levels and oxytocin receptor gene methylation |
url | https://doi.org/10.1038/s41398-023-02524-0 |
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