情感神经环路分子机理的药物基因脑成像研究

杏仁核、前扣带回、脑岛前叶等组成神经环路，参与多种情绪反应，其活动强度及功能连接受基因和社会因素调控，但情感神经环路活动的分子机理尚不清楚。本项目结合脑功能成像、基因和药物、以及心理学等手段，研究基因调控情感神经环路活动的分子机理，旨在（１）通过比较不同基因亚型人群大脑功能磁共振信号，阐明5-羟色胺转运体基因多态性如何影响杏仁核、前扣带回、脑岛前叶等脑区与情绪相关的活动强度和功能连接；（２）通过施用5-羟色胺再摄取抑制剂，阐明5-羟色胺转运蛋白在情感神经环路活动中的作用。发展药物基因脑成像方法，多学科交叉研究情感神经环路活动的分子机理，是本项目的创新之处，可能为实现该重大研究计划的科学目标做出重要贡献。本项目预期研究结果对于理解情感神经环路的基因和分子机理有理论意义，对于理解5-羟色胺再摄取抑制剂等药物在不同基因亚型病人中的治疗作用有临床意义。

The neural circuit consisting of the amygdala, anterior cingulate (ACC) and anterior insular (AI) cortex is engaged in multiple emotional responses. However, the molecular mechanisms underlying the activity of the emotional neural circuit remain unknown. By integrating multiple methods of brain imaging, genetics and drug, and psychology, this project aims to investigate molecular mechanisms of the emotional neural circuit. (1) By comparing functional MRI signals from genotyped adults, we investigate how serotonin transporter gene polymorphisms (5-HTTLPR) influence the activity and functional connectivity in the amygdala，ACC and AI during emotion processing. (2) By applying selective serotonin transporter reuptake inhibitor (SSRI) and placebo to genotyped adults, we investigate different functional roles of molecules such as serotonin transporter (5-HTT) in the emotional neural circuit. The innovation of our project is to develop a pharmacogenetic brain imaging approach to the understanding of molecular mechanisms of the emotional neural circuit　and this may make a great contribution to the scientific goal of the key project. The outcome of our project will help to understand the genetic and molecular mechanisms underlying the function of the key nodes of the emotional neural circuit and drug (e.g., SSRI) efficacy in clinical treatment of patients with different genotypes.