Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms.
Mol Autism
; 12(1): 15, 2021 02 23.
Article
en En
| MEDLINE
| ID: mdl-33622389
ABSTRACT
BACKGROUND:
Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown.METHODS:
The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy 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 multi-center, 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).LIMITATIONS:
The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes.CONCLUSION:
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. TRIAL REGISTRATION A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered 30 October 2014; UMIN Clinical Trials Registry https//upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264).Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sarcosina
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Trastorno Autístico
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Oxitocina
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
Límite:
Adolescent
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Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Autism
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón