Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial

Reactive attachment disorder (RAD) is associated with socially and emotionally withdrawn/inhibited behaviors and reduced neural responses to rewards. Children and adolescents with RAD show aberrant attachment behaviors, and existing psychotherapies are difficult to maintain; therefore, pharmacologic...

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Main Authors: Shinichiro Takiguchi, Kai Makita, Takashi X. Fujisawa, Shota Nishitani, Akemi Tomoda
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Child and Adolescent Psychiatry
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Online Access:https://www.frontiersin.org/articles/10.3389/frcha.2022.1056115/full
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author Shinichiro Takiguchi
Shinichiro Takiguchi
Kai Makita
Takashi X. Fujisawa
Takashi X. Fujisawa
Shota Nishitani
Shota Nishitani
Akemi Tomoda
Akemi Tomoda
Akemi Tomoda
author_facet Shinichiro Takiguchi
Shinichiro Takiguchi
Kai Makita
Takashi X. Fujisawa
Takashi X. Fujisawa
Shota Nishitani
Shota Nishitani
Akemi Tomoda
Akemi Tomoda
Akemi Tomoda
author_sort Shinichiro Takiguchi
collection DOAJ
description Reactive attachment disorder (RAD) is associated with socially and emotionally withdrawn/inhibited behaviors and reduced neural responses to rewards. Children and adolescents with RAD show aberrant attachment behaviors, and existing psychotherapies are difficult to maintain; therefore, pharmacological interventions to aid and boost treatment responses are needed. Oxytocin (OT) administration is known to promote reward functioning. We investigated whether single-use intranasal OT administration improved neural responses during reward processing in patients with RAD compared with healthy controls. Twenty-four male children and adolescents with RAD (10–18 years old) and 27 age- and sex-matched typically developing individuals (10–17 years old) were included in this randomized, double-blind, placebo-controlled, cross-over, functional magnetic resonance imaging study. Following a single intranasal OT (24 IU) or placebo administration, neural responses were investigated using a monetary reward task. In the RAD group, OT significantly increased subjective motivation scores, significantly enhanced activation in the right middle frontal gyrus, and reduced activation in the right precentral gyrus during the monetary reward task. Additional analyses revealed increased activation in the bilateral caudate at a more lenient threshold. Under placebo conditions, the severity of internalizing problems in patients with RAD was negatively correlated with ventral striatal activity. Moreover, the effect of OT on ventral striatum activity was positively associated with the severity of internalizing problems in patients with RAD. Intranasal OT administration enhanced activity in the reward pathway in male children and adolescents with RAD, suggesting that exogenous OT promotes reward processing and reward-related motivational behavior in these individuals. Further investigation is needed to fully understand the neural mechanisms of intranasal OT and identify novel targets for pediatric cases with RAD.Clinical trial registration: UMIN-CTR; UMIN000013215. URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000015419
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publisher Frontiers Media S.A.
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spelling doaj-art-ca8e755f953444cdaf2f0b3c80483e492025-01-21T15:36:18ZengFrontiers Media S.A.Frontiers in Child and Adolescent Psychiatry2813-45402023-01-01110.3389/frcha.2022.10561151056115Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trialShinichiro Takiguchi0Shinichiro Takiguchi1Kai Makita2Takashi X. Fujisawa3Takashi X. Fujisawa4Shota Nishitani5Shota Nishitani6Akemi Tomoda7Akemi Tomoda8Akemi Tomoda9Department of Child and Adolescent Psychological Medicine, University of Fukui Hospital, Fukui, JapanDivision of Developmental Higher Brain Functions, United Graduate School of Child Development, University of Fukui, Fukui, JapanResearch Center for Child Mental Development, University of Fukui, Fukui, JapanDivision of Developmental Higher Brain Functions, United Graduate School of Child Development, University of Fukui, Fukui, JapanResearch Center for Child Mental Development, University of Fukui, Fukui, JapanDivision of Developmental Higher Brain Functions, United Graduate School of Child Development, University of Fukui, Fukui, JapanResearch Center for Child Mental Development, University of Fukui, Fukui, JapanDepartment of Child and Adolescent Psychological Medicine, University of Fukui Hospital, Fukui, JapanDivision of Developmental Higher Brain Functions, United Graduate School of Child Development, University of Fukui, Fukui, JapanResearch Center for Child Mental Development, University of Fukui, Fukui, JapanReactive attachment disorder (RAD) is associated with socially and emotionally withdrawn/inhibited behaviors and reduced neural responses to rewards. Children and adolescents with RAD show aberrant attachment behaviors, and existing psychotherapies are difficult to maintain; therefore, pharmacological interventions to aid and boost treatment responses are needed. Oxytocin (OT) administration is known to promote reward functioning. We investigated whether single-use intranasal OT administration improved neural responses during reward processing in patients with RAD compared with healthy controls. Twenty-four male children and adolescents with RAD (10–18 years old) and 27 age- and sex-matched typically developing individuals (10–17 years old) were included in this randomized, double-blind, placebo-controlled, cross-over, functional magnetic resonance imaging study. Following a single intranasal OT (24 IU) or placebo administration, neural responses were investigated using a monetary reward task. In the RAD group, OT significantly increased subjective motivation scores, significantly enhanced activation in the right middle frontal gyrus, and reduced activation in the right precentral gyrus during the monetary reward task. Additional analyses revealed increased activation in the bilateral caudate at a more lenient threshold. Under placebo conditions, the severity of internalizing problems in patients with RAD was negatively correlated with ventral striatal activity. Moreover, the effect of OT on ventral striatum activity was positively associated with the severity of internalizing problems in patients with RAD. Intranasal OT administration enhanced activity in the reward pathway in male children and adolescents with RAD, suggesting that exogenous OT promotes reward processing and reward-related motivational behavior in these individuals. Further investigation is needed to fully understand the neural mechanisms of intranasal OT and identify novel targets for pediatric cases with RAD.Clinical trial registration: UMIN-CTR; UMIN000013215. URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000015419https://www.frontiersin.org/articles/10.3389/frcha.2022.1056115/fullreactive attachment disorder (RAD)intranasal oxytocinfunctional magnetic resonance imaging (fMRI)rewardchildhood maltreatmentrandomized controlled trial
spellingShingle Shinichiro Takiguchi
Shinichiro Takiguchi
Kai Makita
Takashi X. Fujisawa
Takashi X. Fujisawa
Shota Nishitani
Shota Nishitani
Akemi Tomoda
Akemi Tomoda
Akemi Tomoda
Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial
Frontiers in Child and Adolescent Psychiatry
reactive attachment disorder (RAD)
intranasal oxytocin
functional magnetic resonance imaging (fMRI)
reward
childhood maltreatment
randomized controlled trial
title Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial
title_full Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial
title_fullStr Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial
title_full_unstemmed Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial
title_short Effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder: A randomized controlled trial
title_sort effects of intranasal oxytocin on neural reward processing in children and adolescents with reactive attachment disorder a randomized controlled trial
topic reactive attachment disorder (RAD)
intranasal oxytocin
functional magnetic resonance imaging (fMRI)
reward
childhood maltreatment
randomized controlled trial
url https://www.frontiersin.org/articles/10.3389/frcha.2022.1056115/full
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