Cargando…

Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal...

Descripción completa

Detalles Bibliográficos
Autores principales: Aoki, Y, Watanabe, T, Abe, O, Kuwabara, H, Yahata, N, Takano, Y, Iwashiro, N, Natsubori, T, Takao, H, Kawakubo, Y, Kasai, K, Yamasue, H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378254/
https://www.ncbi.nlm.nih.gov/pubmed/25070538
http://dx.doi.org/10.1038/mp.2014.74
_version_ 1782364037083824128
author Aoki, Y
Watanabe, T
Abe, O
Kuwabara, H
Yahata, N
Takano, Y
Iwashiro, N
Natsubori, T
Takao, H
Kawakubo, Y
Kasai, K
Yamasue, H
author_facet Aoki, Y
Watanabe, T
Abe, O
Kuwabara, H
Yahata, N
Takano, Y
Iwashiro, N
Natsubori, T
Takao, H
Kawakubo, Y
Kasai, K
Yamasue, H
author_sort Aoki, Y
collection PubMed
description The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.
format Online
Article
Text
id pubmed-4378254
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-43782542015-04-07 Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial Aoki, Y Watanabe, T Abe, O Kuwabara, H Yahata, N Takano, Y Iwashiro, N Natsubori, T Takao, H Kawakubo, Y Kasai, K Yamasue, H Mol Psychiatry Original Article The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC. Nature Publishing Group 2015-04 2014-07-29 /pmc/articles/PMC4378254/ /pubmed/25070538 http://dx.doi.org/10.1038/mp.2014.74 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Aoki, Y
Watanabe, T
Abe, O
Kuwabara, H
Yahata, N
Takano, Y
Iwashiro, N
Natsubori, T
Takao, H
Kawakubo, Y
Kasai, K
Yamasue, H
Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial
title Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial
title_full Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial
title_fullStr Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial
title_full_unstemmed Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial
title_short Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial
title_sort oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378254/
https://www.ncbi.nlm.nih.gov/pubmed/25070538
http://dx.doi.org/10.1038/mp.2014.74
work_keys_str_mv AT aokiy oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT watanabet oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT abeo oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT kuwabarah oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT yahatan oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT takanoy oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT iwashiron oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT natsuborit oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT takaoh oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT kawakuboy oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT kasaik oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial
AT yamasueh oxytocinsneurochemicaleffectsinthemedialprefrontalcortexunderlierecoveryoftaskspecificbrainactivityinautismarandomizedcontrolledtrial