Abstract / Summary
Abstract Rationale: Social gaze, particularly eye contact, is commonly reduced in autism spectrum disorder (ASD), potentially reflecting alterations in the oxytocin and opioid systems. Interactive effects of these systems on social gaze have been reported in animal models. Objectives: We tested whether social gaze during a naturalistic face-to-face conversation is modulated by oxytocin, naltrexone, or their combined administration, and whether these effects differ between adults with ASD and neurotypical controls. Methods: Seventy-three adults (34 ASD, 39 controls) completed four double-blind sessions receiving naltrexone (50 mg), oxytocin (10 IU), their combination, or placebo. Across a total of 248 sessions, eye-tracking data was collected to capture gaze patterns towards facial regions. Salivary cortisol was assessed as a secondary physiological measure of hypothalamic–pituitary–adrenal (HPA) axis activity. Results: Individuals with ASD showed atypical gaze patterns relative to controls, characterized by increased gaze to the background, especially among female participants. Contrary to our hypotheses, we found no main effects of medication and no interactions between medication, diagnostic group, or Sex. However, naltrexone reliably increased cortisol levels across groups, indicating engagement of the HPA axis. Conclusions: We found no evidence that oxytocin, naltrexone, or their combination modulated social gaze during face-to-face interaction. Exploratory findings suggest that gaze patterns in ASD may differ between male and female participants, highlighting the importance of considering heterogeneity in social attention research.