title: Serotonin transporter gene polymorphism (5-HTTLPR) influences trait anxiety by modulating the functional connectivity between the amygdala and insula in Han Chinese males.
abstract: A functional polymorphism (5-hydroxytryptamine transporter linked polymorphic region [5-HTTLPR]) in the promoter region of human serotonin transporter gene has been found to be associated with several dimensions of neuroticism and psychopathology, especially anxiety. However, the neural basis underlying the association between 5-HTTLPR and anxiety is less clear. Here, we explored how 5-HTTLPR influenced anxiety by modulating the spontaneous brain activities in Han Chinese. First, we found an association between 5-HTTLPR and anxiety only in the male and not in the female population, where male S/S homozygotes had a significantly higher level of anxiety than male L allele carriers. Then, we examined how 5-HTTLPR influenced anxiety at both regional and network levels in the brain at rest. At the regional level, we found a significantly higher fractional amplitude of low-frequency fluctuations in the amygdala in male S/S homozygotes relative to male L allele carriers. At the network level, male S/S homozygotes showed a weaker resting-state functional connectivity (RSFC) between the amygdala and various regions, including the insula, Heschl's gyrus, lateral occipital cortex, superior temporal gyrus, and hippocampus, and a stronger RSFC between the amygdala and various regions, including the supramariginal gyrus and middle frontal gyrus. However, at both levels, only was the amygdala-insula RSFC correlated with anxiety. Mediation analyses further revealed that the amygdala-insula RSFC mediated the association between 5-HTTLPR and anxiety. In short, our study provided the first empirical evidence that the amygdala-insula RSFC served as the neural basis underlying the association between 5-HTTLPR and anxiety, suggesting a potential neurogenetic susceptibility mechanism for anxiety.
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.|Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, 100875, China.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Song
authors.affiliation: Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, 100875, China.|School of psychology, Beijing Normal University, Beijing, 100875, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology*; D001007:Anxiety / Q000235:genetics; D002540:Cerebral Cortex / Q000502:physiology*; D002681:China; D063132:Connectome; D005260:Female; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000502:physiology*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR; amygdala; anxiety; resting-state functional connectivity
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