TY - JOUR
T1 - Endogenous oxytocin levels in children with autism
T2 - Associations with cortisol levels and oxytocin receptor gene methylation
AU - Evenepoel, Margaux
AU - Moerkerke, Matthijs
AU - Daniels, Nicky
AU - Chubar, Viktoria
AU - Claes, Stephan
AU - Turner, Jonathan
AU - Vanaudenaerde, Bart
AU - Willems, Lynn
AU - Verhaeghe, Johan
AU - Prinsen, Jellina
AU - Steyaert, Jean
AU - Boets, Bart
AU - Alaerts, Kaat
N1 - Funding Information:
This research was supported by internal funding of the KU Leuven (ELG-D2857-C14/17/102), a Doctor Gustave Delport fund of the King Baudouin Foundation, a Branco Weiss fellowship of the Society in Science - ETH Zurich, and an EOS Excellence of Science grant (G0E8718N, HUMVISCAT) granted to KA and BB. ME is supported by an FWO aspirant fundamental fellowship [11N1222N]. JP is supported by an FWO junior postdoctoral fellowship [1257621N]. The funding sources had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6/30
Y1 - 2023/6/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85164202650&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/37391413
U2 - 10.1038/s41398-023-02524-0
DO - 10.1038/s41398-023-02524-0
M3 - Article
C2 - 37391413
SN - 2158-3188
VL - 13
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 235
ER -