title: Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans.
abstract: A large body of research suggests that oxytocin receptor (OXTR) gene polymorphisms may influence both social behaviors and psychiatric conditions related to social deficits, such as autism spectrum disorders (ASDs), schizophrenia, and mood and anxiety disorders. However, the neural mechanism underlying these associations is still unclear. Relative to controls, patients with these psychiatric conditions show differences in brain structure, and in resting state fMRI (rs-fMRI) signal synchronicity among default mode network (DMN) regions (also known as functional connectivity). We used a stepwise imaging genetics approach in 328 healthy young adults to test the hypothesis that 10 SNPs in OXTR are associated with differences in DMN synchronicity and structure of some of the associated brain regions. As OXTR effects may be sex-dependent, we also tested whether our findings were modulated by sex. OXTR rs2254298 A allele carriers had significantly lower rsFC with PCC in a cluster extending from the right fronto-insular cortex to the putamen and globus pallidus, and in bilateral dorsal anterior cingulate cortex (dACC) compared to individuals with the GG genotype; all observed effects were found only in males. Moreover, compared to the male individuals with GG genotype ofrs2254298, the male A allele carriers demonstrated significantly thinner cortical gray matter in the bilateral dACC. Our findings suggest that there may be sexually dimorphic mechanisms by which a naturally occurring variation of the OXTR gene may influence brain structure and function in DMN-related regions implicated in neuropsychiatric disorders.
authors.affiliation: Imaging Genetics Center, Keck/USC School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA; Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 30052, China. Electronic address: wangjunping_tj@163.com.
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Imaging Genetics Center, Keck/USC School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA.
authors.forename: Meredith N
authors.initials: MN
authors.lastname: Braskie
authors.affiliation: Imaging Genetics Center, Keck/USC School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA.
authors.forename: George W
authors.initials: GW
authors.lastname: Hafzalla
authors.affiliation: Imaging Genetics Center, Keck/USC School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Faskowitz
authors.affiliation: Center for Advanced Imaging, University of Queensland, Brisbane QLD 4072, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.affiliation: Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane QLD 4059, Australia.
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane QLD 4072, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 30052, China.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Yu
authors.affiliation: Imaging Genetics Center, Keck/USC School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA. Electronic address: pthomp@usc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D063132:Connectome / Q000379:methods*; D005260:Female; D006179:Gyrus Cinguli / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D012737:Sex Factors; D012919:Social Behavior; D055815:Young Adult
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin
keywords: Default mode network; Functional magnetic resonance imaging; OXTR; Resting-state functional connectivity; Single nucleotide polymorphism