title: Variant in OXTR gene and functional connectivity of the hypothalamus in normal subjects.
abstract: The oxytocin receptor gene (OXTR) rs53576A has been associated with autism spectrum disorders (ASDs). A smaller hypothalamic volume has been reported in healthy male A-allele carriers than in male GG homozygotes and in patients with ASDs than in healthy controls. These findings prompt the hypothesis that male AA homozygotes may have weaker hypothalamic functional connectivity when compared to male G-allele carriers. We calculated local functional connectivity density (FCD) using a voxel-wise data-driven approach based on resting-state functional MRI data in 270 young healthy subjects. Both the main effect of genotype and the gender-by-genotype interaction were considered. Of the whole brain, only the local FCD of the hypothalamus exhibited the main effect of genotype. Post-hoc testing revealed significantly lower local FCD in male AA homozygotes compared to male G-allele carriers although there was only a trend of significance in the gender-by-genotype interaction. We further analyzed the resting-state functional connectivity (rsFC) of the hypothalamic region that demonstrating significant genotype differences in local FCD. We found a significant gender-by-genotype interaction in rsFC between the hypothalamic region and the left dorsolateral prefrontal cortex, but no significant main effect of genotype was found. Post-hoc testing revealed that this rsFC was significantly weaker in male AA homozygotes compared to male G-allele carriers. Our findings identify gender-dependent mechanisms of OXTR rs53576 gene variation impacting the functional connectivity of the hypothalamus in healthy individuals and suggest that these mechanisms are important for understanding ASDs.
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Qin
authors.affiliation: LIAMA Center for Computational Medicine, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yunting
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: LIAMA Center for Computational Medicine, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: jiangtz@nlpr.ia.ac.cn.
authors.forename: Tianzi
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: chunshuiyu@yahoo.cn.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Yu
mesh_terms: D002659:Child Development Disorders, Pervasive / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007031:Hypothalamus / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000473:pathology*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin
keywords: Autism; Functional connectivity; Hypothalamus; Oxytocin receptor; Single nucleotide polymorphism