title: Oxytocin and vasopressin effects on the neural response to social cooperation are modulated by sex in humans.
abstract: 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.
authors.affiliation: Department of Anthropology, Emory University, Atlanta, GA, USA.
authors.forename: Chunliang
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Anthropology, Emory University, Atlanta, GA, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Hackett
authors.affiliation: Department of Psychology, University of Kansas, Lawrence, KS, USA.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: DeMarco
authors.affiliation: Department of Anthropology, Emory University, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Stair
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Haroon
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.|Center for Behavioral Neuroscience, Emory University, Atlanta, GA, USA.|Department of Psychology, University of Zurich, Zurich, Switzerland.
authors.forename: Beate
authors.initials: B
authors.lastname: Ditzen
authors.affiliation: Department of Neural, Biomedical, and Metabolic Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pagnoni
authors.affiliation: Department of Anthropology, Emory University, Atlanta, GA, USA. jrillin@emory.edu.|Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA. jrillin@emory.edu.|Center for Behavioral Neuroscience, Emory University, Atlanta, GA, USA. jrillin@emory.edu.|Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA. jrillin@emory.edu.|Center for Translational Social Neuroscience, Emory University, Atlanta, GA, USA. jrillin@emory.edu.|Department of Anthropology, Department of Psychiatry and Behavioral Sciences, Emory University, 1557 Dickey Drive, Atlanta, GA, 30322, USA. jrillin@emory.edu.
authors.forename: James K
authors.initials: JK
authors.lastname: Rilling
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003299:Cooperative Behavior; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010121:Oxytocin / Q000008:administration & dosage*; D000068956:Prisoner Dilemma; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D012201:Reward; D012727:Sex Characteristics; D014667:Vasopressins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D011619:Psychotropic Drugs; D014667:Vasopressins; D010121:Oxytocin; D010100:Oxygen
keywords: Cooperation; Oxytocin; Sex differences; Vasopressin; fMRI