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Acute oxytocin effects in inferring others’ beliefs and social emotions in people at clinical high risk for psychosis

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André Schmidt, Cathy Davies, Yannis Paloyelis, Nick Meyer, Andrea De Micheli, Valentina Ramella-Cravaro, Umberto Provenzani, Yuta Aoki, Grazia Rutigliano, Marco Cappucciati, Dominic Oliver, Silvia Murguia, Fernando Zelaya, Paul Allen, Sukhi Shergill, Paul Morrison, Steve Williams, David Taylor, Stefan Borgwardt, Hidenori Yamasue & 2 more Philip McGuire, Paolo Fusar-Poli

Original languageEnglish
Article number203
JournalTranslational psychiatry
Issue number1
Accepted/In press26 May 2020
Published1 Dec 2020


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    Uploaded date:26 May 2020

    Version:Accepted author manuscript

  • Schmidt_et_al-2020-Translational_Psychiatry

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    Uploaded date:10 Jun 2020

    Version:Final published version

    Licence:CC BY

King's Authors


Social deficits are key hallmarks of the Clinical High Risk for Psychosis (CHR-P) state and of established psychotic disorders, and contribute to impaired social functioning, indicating a potential target for interventions. However, current treatments do not significantly ameliorate social impairments in CHR-P individuals. Given its critical role in social behaviour and cognition, the oxytocinergic (OT) system is a promising target for novel interventions in CHR-P subjects. In a double- blind, placebo-controlled, crossover design, 30 CHR-P males were studied using functional magnetic resonance imaging (fMRI) on two occasions, once after 40IU self-administered intranasal OT and once after placebo. A modified version of the Sally-Anne task was used to assess brain activation during inferring others’ beliefs and social emotions. The Reading the Mind in the Eyes Test was acquired prior to the first scan to test whether OT effects were moderated by baseline social- emotional abilities. OT did not modulate behavioural performances but reduced activation in the bilateral inferior frontal gyrus compared with placebo while inferring others’ social emotions. Furthermore, the relationship between brain activation and task performance after OT administration was moderated by baseline social-emotional abilities. While task accuracy during inferring others’ social emotion increased with decreasing activation in the left inferior frontal gyrus in CHR-P individuals with low social-emotional abilities, there was no such relationship in CHR-P individuals with high social-emotional abilities. Our findings may suggest that acute OT administration enhances neural efficiency in the inferior frontal gyrus during inferring others’ social emotions in those CHR-P subjects with low baseline social-emotional abilities.

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