Impact of chronic intranasal oxytocin administration on face expression processing in autistic children: a randomized controlled trial using fMRI

Background: Difficulties with (non-verbal) social communication, including facial expression processing, constitute a hallmark of autism. Intranasal administration of oxytocin has been considered a potential therapeutic option for improving social difficulties in autism, either by enhancing the salience of social cues or by reducing the social stress and anxiety experienced in social encounters.

Methods: We recorded fMRI brain activity while presenting neutral, fearful and scrambled faces, to compare the neural face processing signature of autistic children (n = 58) with that of matched non-autistic controls (n = 38). Next, in the autistic children group, we implemented this fMRI face processing task in a double-blind, placebo-controlled, multiple-dose oxytocin clinical trial, to evaluate the impact of four-week repeated oxytocin administration (24 IU daily dose) on brain activity in face processing regions.

Results: No significant diagnostic-group differences were identified between autistic versus non-autistic children with regard to neural face processing. Furthermore, no significant treatment effects were found in the oxytocin clinical trial. However, exploratory analyses (uncorrected for multiple comparisons) demonstrated decreases in brain activity in the left superior temporal sulcus (STS) and inferior frontal region in the oxytocin compared to the placebo group, and change-from-baseline analyses in the oxytocin group revealed significantly reduced neural activity in the core face-processing network (STS, inferior occipital, and posterior fusiform), as well as in amygdala and inferior frontal region.

Conclusion: These findings suggest an attenuating effect of multiple-dose oxytocin administration on neural face processing, potentially supporting the anxiolytic account of oxytocin.