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Oxytocin enhances brain function in children with autism.

ABSTRACT: Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.

SUBMITTER: Gordon I

PROVIDER: S-EPMC3876263 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Oxytocin enhances brain function in children with autism.

Gordon Ilanit I Vander Wyk Brent C BC Bennett Randi H RH Cordeaux Cara C Lucas Molly V MV Eilbott Jeffrey A JA Zagoory-Sharon Orna O Leckman James F JF Feldman Ruth R Pelphrey Kevin A KA

Proceedings of the National Academy of Sciences of the United States of America 20131202 52

Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal ...[more]

PMID: 24297883

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Project description:BackgroundExperimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.MethodsWe conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.ResultsOf the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.ConclusionsThis placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Project description:Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD.In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M?=?13.43 years, SD?=?2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes.Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards.The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.

Project description:Research suggests that children with autism spectrum disorder (ASD) may have reduced empathy, as measured by an impaired contagious yawn response, compared to typically developing (TD) children. Other research has failed to replicate this finding, instead attributing this phenomenon to group differences in attention paid to yawn stimuli. A third possibility is that only a subgroup of children with ASD exhibits the impaired contagious yawn response, and that it can be identified biologically. Here we quantified blood concentrations of the "social" neuropeptide oxytocin (OXT) and evaluated yawning behavior and attention rates during a laboratory task in children with ASD (N?=?34) and TD children (N?=?30) aged 6-12?years. No group difference in contagious yawning behavior was found. However, a blood OXT concentration?×?group (ASD vs. TD) interaction positively predicted contagious yawning behavior (F1,50 ?=?7.4987; P?=?0.0085). Specifically, blood OXT concentration was positively related to contagious yawning behavior in children with ASD, but not in TD children. This finding was not due to delayed perception of yawn stimuli and was observed whether attention paid to test stimuli and clinical symptom severity were included in the analysis or not. These findings suggest that only a biologically defined subset of children with ASD exhibits reduced empathy, as measured by the impaired contagious yawn response, and that prior conflicting reports of this behavioral phenomenon may be attributable, at least in part, to variable mean OXT concentrations across different ASD study cohorts. Autism Res 2019, 12: 1156-1161. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism may contagiously yawn (i.e., yawn in response to another's yawn) less often than people without autism. We find that people with autism who have lower levels of blood oxytocin (OXT), a hormone involved in social behavior and empathy, show decreased contagious yawning, but those who have higher blood OXT levels do not differ in contagious yawning from controls. This suggests that decreased contagious yawning may only occur in a biologically defined subset of people with autism.

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Oxytocin enhances brain function in children with autism.

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Oxytocin enhances brain function in children with autism.

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