title: Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women.
abstract: Anxiety disorders are characterized by hyperactivity in both the amygdala and the anterior insula. Interventions that normalize activity in these areas may therefore be effective in treating anxiety disorders. Recently, there has been significant interest in the potential use of oxytocin (OT), as well as vasopressin (AVP) antagonists, as treatments for anxiety disorders. In this double-blind, placebo-controlled, pharmaco- fMRI study, 153 men and 151 women were randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo and imaged with fMRI as they played the iterated Prisoner's Dilemma game with same-sex human and computer partners. In men, OT attenuated the fMRI response to unreciprocated cooperation (CD), a negative social interaction, within the amygdala and anterior insula. This effect was specific to interactions with human partners. In contrast, among women, OT unexpectedly attenuated the amygdala and anterior insula response to unreciprocated cooperation from computer but not human partners. Among women, AVP did not significantly modulate the response to unreciprocated cooperation in either the amygdala or the anterior insula. However, among men, AVP attenuated the BOLD response to CD outcomes with human partners across a relatively large cluster including the amygdala and the anterior insula, which was contrary to expectations. Our results suggest that OT may decrease the stress of negative social interactions among men, whereas these effects were not found in women interacting with human partners. These findings support continued investigation into the possible efficacy of OT as a treatment for anxiety disorders.
authors.affiliation: Department of Anthropology, Emory University, 1557 Dickey Drive, Atlanta, GA, 30322, USA.|Department of Psychiatry and Behavioral Sciences, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anthropology, Emory University, 1557 Dickey Drive, Atlanta, GA, 30322, 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, 1557 Dickey Drive, Atlanta, GA, 30322, USA.
authors.forename: Chunliang
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Stair
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Haroon
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, 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, 1557 Dickey Drive, Atlanta, GA, 30322, USA. jrillin@emory.edu.|Department of Psychiatry and Behavioral Sciences, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, 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.
authors.forename: James K
authors.initials: JK
authors.lastname: Rilling
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000679:Amygdala / Q000378:metabolism / Q000502:physiology; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D001921:Brain / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D003299:Cooperative Behavior; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007398:Interpersonal Relations; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D012919:Social Behavior; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014667:Vasopressins; D010121:Oxytocin
keywords: Amygdala; Anterior insula; Anxiety; Functional magnetic resonance imaging (fMRI); Oxytocin; Social cooperation