Oxytocin administration enhances insula responses during social reward processing in post-traumatic stress disorder

Rationale: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that can develop after experiencing a traumatic event. Although effective treatment is available, including exposure therapy or cognitive behavioural therapy, about 30% of patients with PTSD do not respond to these treatments. Therefore, currently available treatments need to be improved. Intranasal administration of the neuropeptide oxytocin is a promising candidate for medication-enhanced psychotherapy (MEP), as oxytocin has been shown to increase sensitivity for social reward. This could enhance therapeutic alliance and perceived social support, which are both important determinants of treatment response.

Methods: To explore the potential of intranasal oxytocin for MEP, we conducted a randomized, placebo-controlled, crossover fMRI study in male and female PTSD patients (n = 35, 21 males) and trauma-exposed healthy controls (n = 37, 19 males). We investigated the effects of a single oxytocin administration (40 IU) on neural sensitivity to social reward and punishment (i.e. happy and angry faces). A social incentive delay task was employed to investigate neural responses during social reward and punishment anticipation and consumption. All participants were scanned twice; once after placebo and once after oxytocin administration. Medication order was double-blind and counterbalanced. Repeated-measures analyses of variance (ANOVA) were run on whole brain level and within the striatum, insula and amygdala as regions-of-interest (ROI).

Results: When investigating placebo sessions only, a significant group by stimulus-valence interaction was observed within the insula ROI during social consumption: under placebo, PTSD patients had significantly lower left anterior insula responses to social reward presentation and higher anterior insula responses to social punishment presentation compared to trauma-exposed healthy controls. When investigating placebo and oxytocin sessions combined, a trend significant group by treatment by stimulus-valence interaction was observed during social consumption: Oxytocin enhanced insula responses to social reward and normalized aberrant insula responses to social punishment in PTSD patients, such that under oxytocin PTSD patients no longer significantly differed from controls under placebo. No effects of PTSD or oxytocin were seen during social anticipation.

Conclusions: These findings suggest that intranasal oxytocin administration has beneficial effects on neural sensitivity to social reward and punishment in male and female patients with PTSD. The anterior insula is a central node of the salience network, guiding attention towards salient stimuli in the environment. By increasing insula responses to social reward, oxytocin may restore the decreased sensitivity towards positive social stimuli seen in PTSD patients. As a result, oxytocin may increase perceived social support and facilitate the initiation and maintenance of therapeutic alliance in PTSD, which in turn may positively affect treatment response. Our findings are a promising first step in investigating the therapeutic potential of oxytocin administration in PTSD patients. As a next step, clinical studies are needed to investigate whether these findings translate to a therapeutic setting, and whether oxytocin administration positively affects psychotherapy efficacy.