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A randomized trial shows dose-frequency and genotype may determine the therapeutic efficacy of intranasal oxytocin

Published online by Cambridge University Press:  04 December 2020

Juan Kou
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
Yingying Zhang
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
Feng Zhou
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
Cornelia Sindermann
Affiliation:
Department of Molecular Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
Christian Montag
Affiliation:
Department of Molecular Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
Benjamin Becker
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
Keith M Kendrick
Affiliation:
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
Corresponding
E-mail address:

Abstract

Background

The neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment, it is unclear whether efficacy may be influenced by dose frequency or genotype.

Methods

In a randomized, double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging trial (150 male subjects), we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24 international units) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting-state functional connectivity between the amygdala and prefrontal cortex.

Results

A single dose of oxytocin-reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces, this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting-state functional connectivity were not influenced by either dose-frequency or receptor genotype.

Conclusions

Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.

Type
Original Article
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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