Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism

Annalina V Mayer,Frieder M Paulus,Sanna Stroth,Anne-Kathrin Wermter,Michael Haberhausen,Peter Alter,Thomas Stehr,Sören Krach,Inge Kamp-Becker

doi:10.1038/s41598-021-94407-x

Abstract

Evidence suggests that intranasal application of oxytocin facilitates empathy and modulates its underlying neural processes, which are often impaired in individuals with autism spectrum disorders (ASD). Oxytocin has therefore been considered a promising candidate for the treatment of social difficulties in ASD. However, evidence linking oxytocin treatment to social behavior and brain function in ASD is limited and heterogeneous effects might depend on variations in the oxytocin-receptor gene (OXTR). We examined 25 male ASD patients without intellectual disability in a double-blind, cross-over, placebo-controlled fMRI-protocol, in which a single dose of oxytocin or placebo was applied intranasally. Patients performed three experiments in the MRI examining empathy for other’s physical pain, basic emotions, and social pain. All participants were genotyped for the rs53576 single-nucleotide polymorphism of the OXTR. Oxytocin increased bilateral amygdala responsiveness during the physical pain task for both painful and neutral stimuli. Other than that, there were no effects of oxytocin treatment. OXTR genotype did not significantly interact with oxytocin treatment. Our results contribute to the growing body of empirical literature suggesting heterogenous effects of oxytocin administration in ASD. To draw clinically relevant conclusions regarding the usefulness of oxytocin treatment, however, empirical studies need to consider methods of delivery, dose, and moderating individual factors more carefully in larger samples.

Highlights

Evidence suggests that intranasal application of oxytocin facilitates empathy and modulates its underlying neural processes, which are often impaired in individuals with autism spectrum disorders (ASD)
The present study examined the influence of acute oxytocin administration on neural correlates of empathy in individuals with ASD and how these effects are modulated by oxytocin-receptor gene (OXTR) genotype
Our study does not provide support for effects of a single dose of oxytocin on neural processes underlying an affective route to understanding others in males with ASD without intellectual disability

Summary

Introduction

Evidence suggests that intranasal application of oxytocin facilitates empathy and modulates its underlying neural processes, which are often impaired in individuals with autism spectrum disorders (ASD). One symptom reported by individuals with ASD are difficulties in intuitively empathizing with others’ emotional states, especially in situations that require an integration of complex social information[3,4] These difficulties have been associated with anatomical and functional differences in the empathy n etwork[5,6,7,8,9,10]. Intranasal administration of oxytocin has been found to enhance the ability to share others’ affective and mental states in healthy individuals[15,16] In this context, the insula[17] as well as the amygdala seem to be key target regions in the brain, with oxytocin modulating amygdala responsiveness to emotional faces[18,19,20,21,22] or social stimuli in g eneral[23]. Variations of the oxytocin receptor gene (OXTR) have been associated with individual differences in the capacity and tendency to empathize with others’ emotional states in healthy individuals[25,26,27,28,29,30] and related brain function in individuals with ASD31

Methods

Discussion

Conclusion