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Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms
The author:Go Top Peptide Biotech    Released in:2021年04月13日
摘要:Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms.

Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efcacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efcacy of the neuropeptide underlying the controversial efects of repeated administration; however, the underlying mechanisms remained unknown. 


The current study explored metabolites representing the molecular mechanisms of oxytocin’s efcacy 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 multicenter, 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 (PFDR = 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 (PFDR = 0.006, r = − 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37).

Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptomsOxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms


Effects of intranasal oxytocin on changes in metabolite concentrations and time-course change in effects of oxytocin. ac Individual changes from baseline in the natural logarithm of the mode of the probability density function (log-PDFmode) of neutral facial expression intensity. Plots show changes from baseline of log-PDFmode of neutral facial expression intensity in participants administered placebo (a) or oxytocin (b). Among the participants administered with oxytocin, individuals showing reduction of log-PDFmode of neutral facial expression from baseline to 2 weeks and increase of log-PDFmode neutral facial expression from 2 to 6 weeks were classified as participants exhibiting a time-course change (c). d Plots show changes in plasma DMG levels during the 6-week administration of oxytocin or placebo. Bars indicate mean concentration change in each group


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.


Original source:

Kato, Y., Kuwabara, H., Okada, T. et al. Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms. Molecular Autism 12, 15 (2021). https://doi.org/10.1186/s13229-021-00423-z


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