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Author Notes:

Corresponding author: James K. Rilling, Ph.D., Department of Anthropology, Department of Psychiatry and Behavioral Sciences, Emory University, 1557 Dickey Drive, Atlanta, GA 30322. Phone: 404-727-3062, jrillin@emory.edu.

We thank Susan Rogers, Jianguo Xu and Larry Young for assistance with various aspects of this study. We also thank Ashley DeMarco and Patrick Hackett for assistant in data collection, and Xu Chen for assisting with data analysis.

The authors declare no competing financial interests.

The funding source had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.


Research Funding:

This study was supported by National Institute of Mental Health [grant number R01 MH084068-01A1] and the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Behavioral Sciences
  • Neurosciences
  • Neurosciences & Neurology
  • Cooperation
  • fMRI
  • oxytocin
  • oxytocin receptor gene polymorphism
  • rs53576
  • MEN

A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans


Journal Title:

Genes, Brain and Behavior


Volume 14, Number 7


, Pages 516-525

Type of Work:

Article | Post-print: After Peer Review


Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment.

Copyright information:

© 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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