PMID- 29587625 OWN - NLM STAT- MEDLINE DCOM- 20191003 LR - 20191007 IS - 1866-1955 (Electronic) IS - 1866-1947 (Print) IS - 1866-1947 (Linking) VI - 10 IP - 1 DP - 2018 Mar 27 TI - The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder. PG - 12 LID - 10.1186/s11689-018-9228-y [doi] LID - 12 AB - BACKGROUND: Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. METHODS: In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. RESULTS: Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group x Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. CONCLUSIONS: The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD. FAU - Greene, R K AU - Greene RK AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA. FAU - Spanos, M AU - Spanos M AD - Duke Clinical Research Institute, Duke University, Durham, NC, 27705, USA. AD - Duke Center for Autism and Brain Development, Duke University, Durham, NC, 27705, USA. AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. AD - Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. AD - Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27705, USA. FAU - Alderman, C AU - Alderman C AD - Duke Clinical Research Institute, Duke University, Durham, NC, 27705, USA. AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. AD - Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. FAU - Walsh, E AU - Walsh E AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. FAU - Bizzell, J AU - Bizzell J AD - Duke-UNC Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, 27705, USA. AD - Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. FAU - Mosner, M G AU - Mosner MG AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA. FAU - Kinard, J L AU - Kinard JL AD - Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. FAU - Stuber, G D AU - Stuber GD AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. AD - Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. AD - Neuroscience Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. FAU - Chandrasekhar, T AU - Chandrasekhar T AD - Duke Center for Autism and Brain Development, Duke University, Durham, NC, 27705, USA. AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. FAU - Politte, L C AU - Politte LC AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. AD - Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. FAU - Sikich, L AU - Sikich L AD - Duke Clinical Research Institute, Duke University, Durham, NC, 27705, USA. AD - Duke Center for Autism and Brain Development, Duke University, Durham, NC, 27705, USA. AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. AD - Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27705, USA. FAU - Dichter, G S AU - Dichter GS AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA. dichter@med.unc.edu. AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. dichter@med.unc.edu. AD - Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27514, USA. dichter@med.unc.edu. AD - Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, CB 7155, Chapel Hill, NC, 27599-7155, USA. dichter@med.unc.edu. LA - eng GR - T32 AT003378/AT/NCCIH NIH HHS/United States GR - R21 MH110933/MH/NIMH NIH HHS/United States GR - U54 HD079124/HD/NICHD NIH HHS/United States GR - T32 HD040127/HD/NICHD NIH HHS/United States GR - R01 DA032750/DA/NIDA NIH HHS/United States GR - R37 DA032750/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180327 PL - England TA - J Neurodev Disord JT - Journal of neurodevelopmental disorders JID - 101483832 RN - 50-56-6 (Oxytocin) SB - IM MH - Administration, Intranasal MH - Adolescent MH - Autism Spectrum Disorder/diagnostic imaging/*physiopathology MH - Brain/diagnostic imaging/*drug effects/*physiopathology MH - Child MH - Double-Blind Method MH - Facial Recognition/drug effects/physiology MH - Female MH - Humans MH - Male MH - Neural Pathways/diagnostic imaging/drug effects/physiopathology MH - Oxytocin/*administration & dosage/metabolism MH - Psychomotor Performance MH - Reaction Time MH - *Reward MH - Saliva/chemistry MH - *Social Perception PMC - PMC5870086 OTO - NOTNLM OT - Autism spectrum disorder OT - Oxytocin OT - Reward OT - fMRI COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This protocol was approved by the Institutional Review Boards at Duke University Medical Center and the University of North Carolina at Chapel Hill, and informed consent was obtained from the parent or guardian of each participant before testing. Each participant 12 years old or above also provided verbal and written assent. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/03/29 06:00 MHDA- 2019/10/08 06:00 PMCR- 2018/03/27 CRDT- 2018/03/29 06:00 PHST- 2017/11/03 00:00 [received] PHST- 2018/03/08 00:00 [accepted] PHST- 2018/03/29 06:00 [entrez] PHST- 2018/03/29 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] PHST- 2018/03/27 00:00 [pmc-release] AID - 10.1186/s11689-018-9228-y [pii] AID - 9228 [pii] AID - 10.1186/s11689-018-9228-y [doi] PST - epublish SO - J Neurodev Disord. 2018 Mar 27;10(1):12. doi: 10.1186/s11689-018-9228-y.