Sex differences in the neural and behavioral response to intranasal oxytocin and vasopressin during human social interaction

• Type of Material: Article
• Authors: James Rilling, Emory University; Ashley C. DeMarco, University of Kansas; Patrick D. Hackett, Emory University; Xu Chen, Emory University; Pritam Gautam, Emory University; Sabrina Stair, Emory University; Ebrahim Haroon, Emory University; Richmond Thompson, Emory University; Beate Ditzen, Emory University; Rajan Patel, Emory University; Giuseppe Pagnoni, Emory University
• Language: English
• Date: 2014-01-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.psyneuen.2013.09.022
• Title of Journal or Parent Work: Psychoneuroendocrinology
• ISSN: 0306-4530
• Volume: 39
• Issue: 1
• Start Page: 237
• End Page: 248
• Grant/Funding Information: This facility is supported by the Yerkes National Primate Research Center Base Grant 2P51RR000165-51.; Supported by NIMH Grant R01 MH084068-01A1 and PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program; National Institutes of Health; National Center for Research Resources.; Assay services were provided by the Biomarkers Core Laboratory at the Yerkes National Primate Research Center.
• Keywords: Science & Technology; Neurosciences & Neurology; fMRI; BINDING-SITES; Life Sciences & Biomedicine; COMMUNICATION; EVOLUTION; Endocrinology & Metabolism; COOPERATION; Sex differences; AUTISM SPECTRUM DISORDERS; RECOGNITION; Oxytocin; Cooperation; MATERNAL-BEHAVIOR; Neurosciences; INCREASES; Vasopressin; RAT; Psychiatry; HUMAN BRAIN
• Research Categories: Anthropology, Medical and Forensic; Biology, Neuroscience; Psychology, Behavioral

Abstract

Both oxytocin (OT) and vasopressin (AVP) are known to modulate social behavior, and dysfunction in both systems has been postulated as a potential cause of certain psychiatric disorders that involve social behavioral deficits. In particular, there is growing interest in intranasal OT as a potential treatment for certain psychiatric disorders, and preliminary pre-clinical and clinical studies suggest efficacy in alleviating some of the associated symptoms. However, the vast majority of research participants in these studies have been male, and there is evidence for sexually differentiated effects of nonapeptides in both humans and non-human animals. To date, no study has investigated the effect of intranasal OT on brain function in human males and females within the same paradigm. Previously, in a randomized, placebo-controlled, double-blind fMRI study, we reported effects of intranasal OT and AVP on behavior and brain activity of human males as they played an interactive social game known as the Prisoner's Dilemma Game. Here, we present findings from an identical study in human females, and compare these with our findings from males. Overall, we find that both behavioral and neural responses to intranasal OT and AVP are highly sexually differentiated. In women, AVP increased conciliatory behavior, and both OT and AVP caused women to treat computer partners more like humans. In men, AVP increased reciprocation of cooperation from both human and computer partners. However, no specific drug effects on behavior were shared between men and women. During cooperative interactions, both OT and AVP increased brain activity in men within areas rich in OT and AVP receptors and in areas playing a key role in reward, social bonding, arousal and memory (e.g., the striatum, basal forebrain, insula, amygdala and hippocampus), whereas OT and AVP either had no effect or in some cases actually decreased brain activity in these regions in women. OT treatment rendered neural responses of males more similar to responses of females in the placebo group and vice versa, raising the prospect of an inverted u-shaped dose response to central OT levels. These findings emphasize the need to fully characterize the effects of intranasal OT and AVP in both males and females and at multiple doses before widespread clinical application will be warranted.