title: A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.
abstract: 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.
authors.affiliation: Department of Anthropology, Emory University, Atlanta, GA, USA.|State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China.
authors.forename: C
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Human Genetics.
authors.forename: A
authors.initials: A
authors.lastname: Lori
authors.affiliation: Department of Psychology, Emory University, Atlanta, GA, USA.
authors.forename: I D
authors.initials: ID
authors.lastname: Waldman
authors.affiliation: Department of Translational Research in Psychiatry and Stress-related Disorders, Max-Planck Institute of Psychiatry, Munich, Germany.|Department of Psychiatry and Behavioral Sciences.
authors.forename: E B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: Department of Psychiatry and Behavioral Sciences.
authors.forename: E
authors.initials: E
authors.lastname: Haroon
authors.affiliation: Department of Anthropology, Emory University, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences.|Center for Behavioral Neuroscience.|Yerkes National Primate Research Center.|Center for Translational Social Neuroscience, Emory University, Atlanta, GA, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Rilling
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D001921:Brain / Q000187:drug effects; D003299:Cooperative Behavior; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D012201:Reward; D012737:Sex Factors; D055815:Young Adult
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D010121:Oxytocin
keywords: Cooperation; fMRI; oxytocin; oxytocin receptor gene polymorphism; rs53576