Background
Social cognition — the ability to infer mental states, emotions, and intentions from others’ facial cues — is a core human capacity that is selectively impaired in autism spectrum disorder (ASD), schizophrenia, and borderline personality disorder. Prior to this study, oxytocin’s role in human social cognition had been inferred from animal models but not experimentally tested in controlled human conditions.
Domes and colleagues used the Reading the Mind in the Eyes Test (RMET) — developed by Simon Baron-Cohen and validated as a sensitive measure of “theory of mind” or mental state inference from eyes alone — to test whether intranasal oxytocin could enhance this core social cognitive capacity.
Methods
30 healthy adult male volunteers participated in a double-blind, placebo-controlled, crossover design. Each subject completed both sessions (oxytocin and placebo) with ≥1 week washout:
- Intranasal oxytocin: 24 IU (45 minutes before testing)
- Intranasal placebo
Primary outcome: RMET score — participants view 36 photographs of eyes only and select the best descriptor of the mental state expressed (forced-choice from 4 options). Maximum score: 36.
Control task: Gender recognition from eyes (requires perceptual processing but not mental state inference) to rule out general attention or vision effects.
Key Findings
| Measure | Oxytocin | Placebo | p-value |
|---|---|---|---|
| RMET score | 27.3 ± 0.5 | 25.7 ± 0.6 | 0.019 |
| Gender recognition | No difference | No difference | ns |
- RMET improvement: ~1.6 points (6.2% improvement over placebo baseline)
- Effect was specific to mental state inference — the gender recognition control task showed no oxytocin effect
- Improvement was distributed across the full range of emotional expressions rather than specific to one valence
Clinical Significance
This study established that intranasal oxytocin can acutely enhance the most sensitive behavioral measure of human theory-of-mind — with implications spanning:
- Autism spectrum disorder: ASD is characteristically associated with RMET impairments; subsequent trials tested oxytocin as an ASD social cognition intervention
- Schizophrenia: Social cognition deficits are among the most disabling aspects of schizophrenia — oxytocin augmentation has since been trialed in this population
- Therapeutic window: The 45-minute pre-task administration window is clinically useful — consistent with intranasal kinetics for CNS effects
- Normal range enhancement: The fact that oxytocin improved social cognition in already-healthy volunteers suggests it is potentiating an existing circuit rather than correcting a deficit
Limitations
- Male participants only; oxytocin effects on social cognition show sex differences with estrogen interactions
- RMET is a laboratory measure; real-world social cognition involves dynamic processing not captured by static photographs
- No neural imaging — the circuit-level mechanism of RMET improvement was inferred but not directly demonstrated
- Long-term or repeated dosing effects on social cognitive function are unknown