Oxytocin therapy for core symptoms in autism spectrum disorder: An updated meta-analysis of randomized controlled trials

Wang, Yue; Wang, Meng-Jie; Rong, Yuluo; He, Huang; Yang, Chang-Jiang

doi:10.1016/j.rasd.2019.03.007

Cited by 29 publications

(22 citation statements)

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“…Overall, the results from the present study are in line with current meta-analytic evidence suggesting that, on average, intranasal oxytocin only has small and sometimes non-significant effects on social cognition and social functioning in individuals with ASD [43,89]. This evidence is further supported by a recent large-scale clinical trial showing that daily administration of oxytocin did not significantly influence social behaviors in 106 men with ASD [90].…”

Section: Discussionsupporting

confidence: 90%

“…This evidence has led to a rising interest in intranasal oxytocin as a potential treatment of social symptoms in ASD. Several clinical trials have investigated the effects of a single or repeated doses of oxytocin, to date with overall inconclusive results [43,44]. However, clinical studies using functional magnetic resonance imaging (fMRI) suggest that oxytocin may influence regions within the reward circuit in autistic individuals.…”

Section: Introductionmentioning

confidence: 99%

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No support for oxytocin modulation of reward-related brain function in autism: evidence from a randomized controlled trial

Mayer

Preckel

Ihle

et al. 2021

Preprint

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Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. Since intranasal oxytocin has been shown to modulate activation of the brain's reward circuit, oxytocin could be a useful tool to ameliorate the processing of social rewards in ASD and thus improve social difficulties. In this randomized, double-blind, placebo-controlled, crossover fMRI study, we examined effects of a 24 IU dose of intranasal oxytocin on reward-related brain function in 37 men with an ASD diagnosis and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards. Apart from a specific interaction effect in a single voxel within the left amygdala during the receipt of rewards, oxytocin did not influence neural processes related to the anticipation or consumption of social or monetary rewards in either group. Exploratory analyses suggested that oxytocin may increase ventral striatum sensitivity to monetary, but not social rewards, in individuals with high levels of self-reported anxiety, depression, alexithymia, and autistic traits irrespective of an ASD diagnosis. There were no significant differences in reward-related brain function between the two groups under placebo. Overall, our results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD without intellectual impairment. How and if oxytocin can be beneficial in the treatment of social difficulties in ASD needs to be addressed by examining moderating influences of individual differences and context on reward-related oxytocin effects.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

No support for oxytocin modulation of reward-related brain function in autism: evidence from a randomized controlled trial

Mayer

Preckel

Ihle

et al. 2021

Preprint

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“…However, in a paper published in 2019 by Wang et al, the authors conducted a systematic review and meta-analysis of these studies and pointed out that intranasal administration of OXT, in comparison with placebo, presented no significant effect on core symptoms of ASD [social function: standardized mean difference (SMD) = 0.03; 95% confidence interval (CI): −0.19 to 0.25; p = 0.7; repetitive behaviors: SMD = 0.01; 95% CI: −0.26 to 0.27; p = 0.9]. The overall heterogeneity of analyzed studies was below 50% and equaled I 2 = 46.4% ( p = 0.025) for social functioning and I 2 = 37% ( p = 0.12) for repetitive behaviors (26). OXT and AVP receptors are G-protein-coupled receptors consisting of seven transmembrane domains.…”

Section: Introductionmentioning

confidence: 94%

Systematic Review of Literature on Single-Nucleotide Polymorphisms Within the Oxytocin and Vasopressin Receptor Genes in the Development of Social Cognition Dysfunctions in Individuals Suffering From Autism Spectrum Disorder

2019

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Introduction: Autism spectrum disorder (ASD) is found in virtually all population groups regardless of ethnic or socioeconomic backgrounds. Among others, dominant symptoms of autism persistent throughout its course of development include, inter alia, qualitative disorders of social communication and social interactions. Numerous studies have been performed on animal models as well as groups of healthy individuals to assess the potential role of oxytocinergic and vasopresynergic systems in normal social functioning. These studies have also discussed their potential participation in the development of social cognition dysfunctions in the course of ASD. This literature review aimed to identify studies examining single-nucleotide polymorphisms of the oxytocin (OXT) and arginine vasopressin (AVP) receptor genes and their differential effects on social cognitive dysfunction in the development of ASD. Methods: A systematic review of literature published within the last 10 years and accessible in PubMed, Google Scholar, Cochrane Library, and APA PsycNET databases was conducted by each author separately. Inclusion criteria required that articles should 1) be published between January 2008 and August 2018; 2) be published in English or Polish; 3) be located in periodical publications; 4) focus on the role of polymorphisms within oxytocin and vasopressin receptor genes in autistic population; 5) provide a clear presentation of the applied methodology; and 6) apply proper methodology. Results: From the 491 studies qualified to the initial abstract analysis, 15 met the six inclusion criteria and were included in the full-text review. Conclusions: The analysis of available literature seems to indicate that there is an association between social cognition dysfunctions in the course of autism and selected alleles of polymorphisms within the OXT receptor AVP 1A receptor genes. However, previous studies neither specify the nature of this association in an unequivocal way nor select genotypes that are the basis for this association.

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“…As a phase 2 study, SOARS-B was designed be an adequately powered test of the hypothesis that sustained administration of intranasal oxytocin improves social function in ASD, while evaluating its safety and tolerability. Prior trials have been underpowered, and, while individual studies have suggested that intranasal oxytocin may benefit social function [62][63][64][65][66], meta-analyses have found no significant benefit across studies [67][68][69]. The variability in these studies makes it difficult to draw conclusions, including differences in dose or duration of treatment as well as participant characteristics, such as age or cognitive function.…”

Section: Discussionmentioning

confidence: 99%

“…Repeated administration of intranasal oxytocin has now been investigated in several small randomized, controlled trials, with sample sizes ranging from 13 to 53 individuals with ASD per treatment group. Individual studies have reported benefit for social function [62][63][64] or social attention/cognition [65,66]; whereas meta-analyses suggest no significant benefit for social function or social cognition [67][68][69] despite a limited ability to draw conclusions due to differing study designs, including oxytocin formulation, participant age, duration of treatment, primary outcome measure, and statistical analysis.…”

Section: Study Rationalementioning

confidence: 99%

Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B)

Spanos

Chandrasekhar

Kim

et al. 2020

Contemporary Clinical Trials

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To describe the rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B). Method: This phase 2 clinical trial was designed to evaluate the use of intranasal oxytocin treatment to improve social difficulties in individuals with autism spectrum disorder (ASD). In total, 290 participants ages 3 to 17 years with a DSM-5 diagnosis of ASD were enrolled to receive 24 weeks of treatment with either oxytocin or a matched placebo at one of seven collaborating sites. Participants were subsequently treated with open-label oxytocin for 24 additional weeks. Post-treatment assessments were done approximately 4 weeks after treatment discontinuation. Plasma oxytocin and oxytocin receptor gene (OXTR) methylation level were measured at baseline, and week 8, 24 and 36 to explore potential relationships between these biomarkers and treatment response. Results: This report describes the rationale, design, and methods of the SOARS-B clinical trial. Conclusions: There is a tremendous unmet need for safe and effective pharmacological treatment options that target the core symptoms of ASD. Several studies support the hypothesis that intranasal oxytocin could improve social orienting and the salience of social rewards in ASD, thereby enhancing reciprocal social behaviors. However, due to conflicting results from a number of pilot studies on the prosocial effects of exogenous oxytocin, this hypothesis remains controversial and inconclusive. SOARS-B is the best powered study to date to address this hypothesis and promises to improve our understanding of the safety and efficacy of intranasal oxytocin in the treatment of social deficits in children with ASD.

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Oxytocin therapy for core symptoms in autism spectrum disorder: An updated meta-analysis of randomized controlled trials

Cited by 29 publications

References 50 publications

No support for oxytocin modulation of reward-related brain function in autism: evidence from a randomized controlled trial

No support for oxytocin modulation of reward-related brain function in autism: evidence from a randomized controlled trial

Systematic Review of Literature on Single-Nucleotide Polymorphisms Within the Oxytocin and Vasopressin Receptor Genes in the Development of Social Cognition Dysfunctions in Individuals Suffering From Autism Spectrum Disorder

Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B)

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