Oxytocinergic Modulation of Threat-Specific Amygdala Sensitization in Humans Is Critically Mediated by Serotonergic Mechanisms

  • Congcong Liu
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Chunmei Lan
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Keshuang Li
    Affiliations
    School of Psychology and Cognitive Science, East China Normal University, Shanghai, China
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  • Feng Zhou
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Shuxia Yao
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Lei Xu
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Ning Yang
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Xinqi Zhou
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Jiaxin Yang
    Affiliations
    State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute of Brain Research, Beijing Normal University, Beijing, China
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  • Xue Yong
    Affiliations
    State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute of Brain Research, Beijing Normal University, Beijing, China
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  • Yina Ma
    Affiliations
    State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute of Brain Research, Beijing Normal University, Beijing, China
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  • Dirk Scheele
    Affiliations
    Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany

    Department of Psychiatry, School of Medicine & Health Sciences, University of Oldenburg, Oldenburg, Germany
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  • Keith M. Kendrick
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Benjamin Becker
    Correspondence
    Address correspondence to Benjamin Becker, Ph.D.
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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Published:April 21, 2021DOI:https://doi.org/10.1016/j.bpsc.2021.04.009

      Abstract

      Background

      Overarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking.

      Methods

      To determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/desensitization, we conducted a parallel-group, randomized, placebo-controlled, double-blind experiment during which 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion or the corresponding placebo-control protocol before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity toward threatening stimuli (angry faces) as assessed by functional magnetic resonance imaging served as the primary outcome.

      Results

      No main or interaction effects of treatment on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization, and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with acute tryptophan depletion.

      Conclusions

      The present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization, and adjunct upregulation of 5-HT neurotransmission may facilitate OXT’s anxiolytic potential.

      Keywords

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