Oxytocin (OT) circuitry plays a major role in the mediation of prosocial behavior. Individuals with autism spectrum disorder (ASD) are characterized by impairments in social interaction and communication and have been suggested to display deficiencies in central OT mechanisms. The current preregistered meta-analysis evaluated potential group differences in endogenous OT levels between individuals with ASD and neurotypical (NT) controls. We included 18 studies comprising a total of 1422 participants. We found that endogenous OT levels are lower in children with ASD as compared to NT controls (n = 1123; g = −0.60; p = 0.006), but this effect seems to disappear in adolescent (n = 152; g = −0.20; p = 0.53) and adult populations (n = 147; g = 0.27; p = 0.45). Secondly, while no significant subgroup differences were found in regard to sex, the group difference in OT levels of individuals with versus without ASD seems to be only present in the studies with male participants (n = 814; g = −0.44; p = 0.08) and not female participants (n = 192; g = 0.11; p = 0.47). More research that employs more homogeneous methods is necessary to investigate potential developmental changes in endogenous OT levels, both in typical and atypical development, and to explore the possible use of OT level measurement as a diagnostic marker of ASD.

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Background Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established. Methods A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8–12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin. Results In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness. Limitations Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities. Conclusions Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors. Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE).

The neuropeptide oxytocin (OXT) is suggested to exert an important role in human social behaviors by modulating the salience of social cues. To date, however, there is mixed evidence whether a single dose of OXT can improve the behavioral and neural sensitivity for emotional face processing. To overcome difficulties encountered with classic event-related potential studies assessing stimulus-saliency, we applied frequency-tagging EEG to implicitly assess the effect of a single dose of OXT (24 IU) on the neural sensitivity for positive and negative facial emotions.Neutral faces with different identities were presented at 6 Hz, periodically interleaved with an expressive face (angry, fearful, and happy, in separate sequences) every fifth image (i.e., 1.2 Hz oddball frequency). These distinctive frequency tags for neutral and expressive stimuli allowed direct and objective quantification of the neural expression-categorization responses. The study involved a doubleblind, placebo-controlled, cross-over trial with 31 healthy adult men. Contrary to our expectations, we did not find an effect of OXT on facial emotion processing, neither at the neural, nor at the behavioral level. A single dose of OXT did not evoke social enhancement in general, nor did it affect social approach-avoidance tendencies. Possibly ceiling performances in facial emotion processing might have hampered further improvement.