Oxytocin Treatment Modulates Social Affect in Autism

Background: Persons with the diagnosis of Autism Spectrum Disorder (ASD) are characterized by substantial social deficits. One of the core symptoms is the reduced capacity to intuitively represent their own and others’ mental states (1–3). However, it has remained unresolved, whether persons with the diagnosis of ASD can empathically share others’ feeling states in an embodied manner (4). This deficit has been attributed to malfunctions of the interoceptive cortex (5), a network comprising the anterior insula cortex (AIC) and the anterior cingulate cortex (ACC) (4, 6). First fMRI studies revealed that intranasal administration of the neuropeptide oxytocin modulates social processing on a behavioral and neural level (7, 8) in healthy participants, while an in-depth investigation of the effects of oxytocin on social processes underlying neural networks in ASD is still lacking.

Objectives: In the present study we aimed at characterizing the effects of intranasal oxytocin treatment on the neural pathways involved in social affect in a group of persons with ASD. We pursued this question on three levels of affective experiences: understanding others basic emotional states (‘Emotions’), sharing others physical pain (‘Physical Pain’), and more complex social pain (‘Social Pain’). We hypothesized that oxytocin treatment would modulate social affective experiences and activity in underlying neural networks compared to the placebo condition.

Methods: Twenty-six young men who matched the DSM IV criteria for ASD and who had a confirmed ICD-10 diagnosis of high-functioning ASD underwent a double-blind, cross-over, placebo controlled fMRI protocol including three experiments to examine social affect on distinct levels. Stimuli within all three conditions consisted of pictures or sketches displaying another either being in a sad, neutral or happy mood (‘Emotions’), showing another’s physically painful bodily injury or non-painful situation (‘Physical Pain’), or a complex social scenario depicting a protagonist threatening his or her social integrity (‘Social Pain’) (9). Stimuli were presented for 6-12s, followed by a rating period to indicate the intensity of the vicarious embarrassment experience with a button press and low-level baseline.

Results: On the behavioural level we observe that oxytocin only slightly attenuates the affective response across the different domains of social affect. This was complemented by the fMRI data yielding a more distributed engagement in brain areas implicated in processing of arousal and affect as well as mentalizing regions.

Conclusions: The present results offer a new perspective on how intranasal oxytocin administration modulates brain networks for social affect in patients diagnosed with ASD. While our results show that persons with high-functioning ASD are capable to correctly assess basic emotions, physical pain as well as more complex social pain experiences, oxytocin treatment still attenuates the self-reported social affect. The underlying brain networks, in particular those implicated in processing of arousal and mentalizing show similar effect, highlighting a potential neural system mechanism for oxytocin treatment in ASD.