Oxytocin and vasopressin effects on the neural response to social cooperation are modulated by sex in humans
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Recent research has examined the effects of oxytocin (OT) and vasopressin (AVP) on human social behavior and brain function. However, most participants have been male, while previous research in our lab demonstrated sexually differentiated effects of OT and AVP on the neural response to reciprocated cooperation. Here we extend our previous work by significantly increasing the number of participants to enable the use of more stringent statistical thresholds that permit more precise localization of OT and AVP effects in the brain. In a double-blind, placebo-controlled study, 153 men and 151 women were randomized to receive 24 IU intranasal OT, 20 IU intranasal AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner’s Dilemma Game with same-sex partners. Sex differences were observed for effects of OT on the neural response to reciprocated cooperation, such that OT increased the caduate/putamen response among males, whereas it decreased this response among females. Thus, 24 IU OT may increase the reward or salience of positive social interactions among men, while decreasing their reward or salience among women. Similar sex differences were also observed for AVP effects within bilateral insula and right supramarginal gyrus when a more liberal statistical threshold was employed. While our findings support previous suggestions that exogenous nonapeptides may be effective treatments for disorders such as depression and autism spectrum disorder, they caution against uniformly extending such treatments to men and women alike.
KeywordsOxytocin Vasopressin fMRI Cooperation Sex differences
We thank Susan Rogers, Jianguo Xu and Larry Young for assistance with various aspects of this study. 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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conflict of interest
Chunliang Feng, Patrick D. Hackett, Ashley C. DeMarco, Xu Chen, Sabrina Stair, Ebrahim Haroon, Beate Ditzen, Giuseppe Pagnoni and James K. Rilling declare that they have no conflict of interest.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all subjects for being included in the study.
- Campbell, A., Ruffman, T., Murray, J., & Glue, P. (2014). Oxytocin improves emotion recognition for older males. Neurobiology of Aging (ahead-of-print), 1–13.Google Scholar
- Cardoso, C., Orlando, M. A., Brown, C. A., & Ellenbogen, M. A. (2014). Oxytocin and enhancement of the positive valence of social affiliation memories: An autobiographical memory study. Social neuroscience (ahead-of-print), 1–10.Google Scholar
- Dodhia, S., Hosanagar, A., Fitzgerald, D. A., Labuschagne, I., Wood, A. G., Nathan, P. J., et al. (2014). Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder. Neuropsychopharmacology (ahead of print).Google Scholar
- Knafo, A., Israel, S., Darvasi, A., Bachner-Melman, R., Uzefovsky, F., Cohen, L., et al. (2008). Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA. Genes, Brain and Behavior, 7(3), 266–275.CrossRefGoogle Scholar
- Lynn, S. K., Hoge, E. A., Fischer, L. E., Barrett, L. F., & Simon, N. M. (2014). Gender differences in oxytocin-associated disruption of decision bias during emotion perception. Psychiatry Research (ahead of print), 1–22.Google Scholar
- Macdonald, K., & Feifel, D. (2013). Helping oxytocin deliver: considerations in the development of oxytocin-based therapeutics for brain disorders. Frontiers in Neuroscience, 7(35), 1–21.Google Scholar
- Preckel, K., Scheele, D., Kendrick, K. M., Maier, W., & Hurlemann, R. (2014). Oxytocin facilitates social approach behavior in women. Frontiers in Behavioral Neuroscience, 8(191), 1–9.Google Scholar
- Striepens, N., Kendrick, K. M., Hanking, V., Landgraf, R., Wüllner, U., Maier, W., et al. (2013). Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans. Scientific Reports, 3(3440), 1–5.Google Scholar