title: Oxytocin receptor gene rs53576 polymorphism modulates oxytocin-dopamine interaction and neuroticism traits--a SPECT study.
abstract: Brain oxytocin and dopamine systems interact to modulate social cognitive behavior. Whether the interactions are modulated by oxytocin receptor (OXTR) gene variations remains unclear. Considering the dopamine transporter (DAT) availability as an endophenotype and the degree of dopamine-mediated neuroticism as a phenotype of the OXTR genotypes, the current molecular imaging study used [(99m)Tc]TRODAT-1 single photon emission computed tomography (SPECT) to measure the striatal DAT availability and the 57-item Maudsley Personality Inventory to measure neuroticism personality traits in healthy individuals to investigate (A) the correlation between the rs53576 (G/A) of OXTR and the striatal DAT availability, (B) the correlation between the peripheral oxytocin level and striatal DAT availability among different OXTR rs53576 (G/A) genotypes, and (C) whether neuroticism traits could be modified by oxytocin in certain OXTR rs53576 genotypes. The results showed that the striatal DAT availability in the AG+GG group was significantly lower than that in the AA group (2.08±0.47 vs. 1.90±0.32, p=0.04). Only individuals with one or two copies of the G allele of rs53576 showed a negative correlation between DAT availability and oxytocin level (r=-0.41, p=0.002). Furthermore, the oxytocin×DAT interaction was significantly correlated with the MPI neuroticism score in the AA group. Further analyses showed that the DAT availability was correlated with the neuroticism score only in the AA group with a low oxytocin level (r=0.74, p=0.002). The results indicated that the OXTR rs53576 is connected with the striatal DAT availability in vivo and modulates the interactions between the oxytocinergic and dopaminergic systems. Carriers with a specific rs53576 OXTR genotype may present a greater biological sensitivity as well as stress reactivity in terms of environmental adaptation.
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tianan, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei Hung
authors.initials: WH
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I Hui
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan; Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kao Chin
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Mei Hung
authors.initials: MH
authors.lastname: Chi
authors.affiliation: Department of Nuclear Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Nan-Tsing
authors.initials: NT
authors.lastname: Chiu
authors.affiliation: Department of Nuclear Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Wei Jen
authors.initials: WJ
authors.lastname: Yao
authors.affiliation: Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
authors.affiliation: Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yen Kuang
authors.initials: YK
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Addiction Research Center, National Cheng Kung University, Tainan, Taiwan. Electronic address: chenps@mail.ncku.edu.tw.
authors.forename: Po See
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075384:Neuroticism; D010121:Oxytocin / Q000378:metabolism*; D010551:Personality / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C569600:OXTR protein, human; D018045:Receptors, Oxytocin; D010121:Oxytocin; D004298:Dopamine
keywords: Dopamine transporter; Oxytocin receptor; Single nucleotide polymorphism; rs53576