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A new study in Molecular Autism has found that a four-week course of oxytocin nasal spray in children with autism spectrum disorder was associated with decreased activity in brain regions responsible for processing faces. This reduction in brain activity suggests that oxytocin might make faces less attention-grabbing for these children, potentially easing social anxiety. These findings could support the idea that oxytocin’s benefits come from reducing social stress, rather than simply making social cues more appealing.
Autism spectrum disorder is a developmental condition that often includes difficulties with social interaction and communication. One of the challenges individuals with autism may face is understanding social cues from faces, which can be important for navigating social situations. Currently, there are no medications specifically designed to target these social communication difficulties in autism.
Oxytocin has been of interest because it plays a role in social behaviors and can be easily administered as a nasal spray. Previous studies exploring how oxytocin impacts face processing have yielded mixed results. Some research has indicated that oxytocin might increase brain activity in areas related to face processing, suggesting it enhances attention to social information.
Other studies, however, have pointed to the opposite effect, with oxytocin reducing brain activity, potentially by lessening social stress. The researchers hypothesized that these differing results could be due to whether oxytocin was given as a single dose or over a longer period. To clarify this, their current study focused on the effects of repeated doses of oxytocin over several weeks on how children with autism process faces.
“Autism is a complex condition, especially in terms of social difficulties,” said study author Matthijs Moerkerke, a postdoctoral researcher at the Center for Developmental Psychiatry at KU Leuven. “Oxytocin, known as the ‘cuddle hormone,’ has been studied for its potential to enhance social cues (like faces) or reduce social anxiety in autism. While acute oxytocin effects have been explored, its long-term impact on the brain in autistic children remains unknown. Therefore, my interest in this topic, to examine how chronic oxytocin administration affects brain activity during facial expression processing in autism.”
To conduct their study, the researchers recruited school-aged children diagnosed with autism and a comparison group of children without autism. The children with autism were randomly assigned to receive either oxytocin or a placebo nasal spray twice daily for four weeks. Neither the participants nor the researchers knew who was receiving oxytocin and who was receiving the placebo, a method called a double-blind study. The children in the comparison group, who did not have autism, did not receive any nasal spray.
All children participated in functional magnetic resonance imaging, a brain scanning technique that measures brain activity by detecting changes in blood flow. The children with autism underwent brain scans both before starting the four-week treatment and after completing it. The comparison group was scanned only once, at the beginning of the study. During the brain scan, children were shown images of faces displaying either neutral or fearful expressions, as well as scrambled images that served as a control. These images were presented in blocks, alternating between different types of faces and a fixation cross, which was a simple visual cue to focus on.
To ensure the children were paying attention to the images, they were given a simple task to perform during the scan. They were instructed to press a button whenever the gender of the face changed or when a scrambled image briefly changed to a simple face outline. This task was designed to keep them focused on the screen without specifically requiring them to process the emotions on the faces.
The researchers analyzed the brain scan data to compare brain activity between the groups and to see how brain activity changed after oxytocin treatment. Initially, they compared the brain activity of children with and without autism at the start of the study. Surprisingly, they found no significant differences in brain activity related to face processing between the two groups at the beginning.
However, when they examined the effects of the four-week oxytocin treatment in children with autism, they observed some interesting changes. Compared to the placebo group, children who received oxytocin showed reduced brain activity in the left superior temporal sulcus and the left inferior frontal region after the treatment period.
Looking more closely at the oxytocin group alone, the researchers found that brain activity in several key face processing regions decreased significantly from before to after the four-week treatment. These regions included not only the superior temporal sulcus and inferior frontal region, but also the inferior occipital region and posterior fusiform region, as well as the amygdala. These reductions in brain activity were not observed in the placebo group.
“We expected oxytocin to increase brain activity related to facial expression processing, making social cues more noticeable,” Moerkerke told PsyPost. “Instead, we saw a slight reduction in neural activity, suggesting a stress-reducing effect. This could mean oxytocin, administered over a longer period (4 weeks), helps autistic children feel more at ease in social situations rather than enhancing facial expression processing. By lowering social stress, oxytocin may support more comfortable and natural social interactions.”
Looking ahead, the researchers emphasized the need for future studies to further explore the differences between single-dose and long-term oxytocin administration.
“Single doses are often paired with tasks like facial recognition, where oxytocin improves performance, while chronic use showed more stress-reducing effects,” Moerkerke said. “Future research should combine chronic oxytocin use with (positive) social tasks or behavioral therapy to evaluate its effects. This is something our lab is currently working on.”
The study, “Impact of chronic intranasal oxytocin administration on face expression processing in autistic children: a randomized controlled trial using fMRI,” was authored by Matthijs Moerkerke, Nicky Daniels, Stephanie Van der Donck, Tiffany Tang, Jellina Prinsen, Elahe’ Yargholi, Jean Steyaert, Kaat Alaerts, and Bart Boets.