title: Oxytocin's effect on resting-state functional connectivity varies by age and sex.
abstract: The neuropeptide oxytocin plays a role in social cognition and affective processing. The neural processes underlying these effects are not well understood. Modulation of connectivity strength between subcortical and cortical regions has been suggested as one possible mechanism. The current study investigated effects of intranasal oxytocin administration on resting-state functional connectivity between amygdala and medial prefrontal cortex (mPFC), as two regions involved in social-cognitive and affective processing. Going beyond previous work that largely examined young male participants, our study comprised young and older men and women to identify age and sex variations in oxytocin's central processes. This approach was based on known hormonal differences among these groups and emerging evidence of sex differences in oxytocin's effects on amygdala reactivity and age-by-sex-modulated effects of oxytocin in affective processing. In a double-blind design, 79 participants were randomly assigned to self-administer either intranasal oxytocin or placebo before undergoing resting-state functional magnetic resonance imaging. Using a targeted region-to-region approach, resting-state functional connectivity strength between bilateral amygdala and mPFC was examined. Participants in the oxytocin compared to the placebo group and men compared to women had overall greater amygdala-mPFC connectivity strength at rest. These main effects were qualified by a significant three-way interaction: while oxytocin compared to placebo administration increased resting-state amygdala-mPFC connectivity for young women, oxytocin did not significantly influence connectivity in the other age-by-sex subgroups. This study provides novel evidence of age-by-sex differences in how oxytocin modulates resting-state brain connectivity, furthering our understanding of how oxytocin affects brain networks at rest.
authors.affiliation: Department of Psychology, University of Florida, P.O. Box 112250, Gainesville, FL 32611-2250, USA; Department of Aging and Geriatric Research, Cognitive Aging and Memory Program, Clinical Translational Research Program (CAM-CTRP), Institute on Aging, University of Florida, 2004 Mowry Road, Gainesville, FL 32611, USA. Electronic address: natalie.ebner@ufl.edu.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Ebner
authors.affiliation: Department of Aging and Geriatric Research, Cognitive Aging and Memory Program, Clinical Translational Research Program (CAM-CTRP), Institute on Aging, University of Florida, 2004 Mowry Road, Gainesville, FL 32611, USA; Department of Biostatistics, University of Florida, 2004 Mowry Road, Gainesville, FL 32611, USA. Electronic address: huaihouchen@phhp.ufl.edu.
authors.forename: Huaihou
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Aging and Geriatric Research, Cognitive Aging and Memory Program, Clinical Translational Research Program (CAM-CTRP), Institute on Aging, University of Florida, 2004 Mowry Road, Gainesville, FL 32611, USA. Electronic address: eporges@ufl.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Porges
authors.affiliation: Department of Psychology, University of Florida, P.O. Box 112250, Gainesville, FL 32611-2250, USA. Electronic address: lintian0527@ufl.edu.
authors.forename: Tian
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Psychology, Stockholm University, Frescati Hagväg 14, Room 320, SE-106 91 Stockholm, Sweden. Electronic address: hakan.fischer@psychology.su.se.
authors.forename: Håkan
authors.initials: H
authors.lastname: Fischer
authors.affiliation: Department of Psychiatry, University of California, 200 W. Arbor Drive, San Diego, CA 92103-8218, USA. Electronic address: dfeifel@ucsd.edu.
authors.forename: David
authors.initials: D
authors.lastname: Feifel
authors.affiliation: Department of Aging and Geriatric Research, Cognitive Aging and Memory Program, Clinical Translational Research Program (CAM-CTRP), Institute on Aging, University of Florida, 2004 Mowry Road, Gainesville, FL 32611, USA. Electronic address: roncohen@ufl.edu.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Cohen
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000367:Age Factors; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D010121:Oxytocin / Q000032:analysis / Q000378:metabolism* / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects; D012737:Sex Factors
chemical_list: D010121:Oxytocin
keywords: Aging; Amygdala; Medial prefrontal cortex; Oxytocin; Resting-state functional connectivity; Sex