五羟色胺转运体基因的多态性对自发脑活动的影响摘　要【研究背景】在人类五羟色胺转运体基因（SLC6A4）的启动子区存在一个功能多态位点，包括长等位基因（L）和短等位基因（S）。这个多态位点可能与情感性精神障碍、焦虑症状特质的发生有关。功能磁共振研究表明，在对负性情感图片进行加工时，S等位基因携带者个体的杏仁核活动强度高于L等位基因纯合子个体，而腹内侧前额叶皮层的活动则相反。这表明，五羟色胺转运体基因可以通过调控大脑对外界刺激的反应来影响个体的行为表现。然而，在没有特定任务的状态下，不同基因型个体的大脑的自发活动是否存在显著差异的研究还很少，而自发活动的不同可能是诱发大脑在任务状态时活动差异的原因，对大脑自发活动状态的了解可以加深对任务状态时大脑活动的解释。 【研究目的】1、 探讨在静息状态时，不同基因型被试其杏仁核和腹内侧前额叶皮层活动的差别；2、 探讨5-HTTLPR的不同基因型对个体杏仁核和腹内侧前额叶皮层的活动的影响是否存在性别差异；【研究方法】 在北京师范大学大一新生入学体检抽血时，征得被试本人同意后抽取4毫升静脉血用于基因多态性检测，根据基因多态性检测结果，随机选取了其中37名被试进行静息态脑功能磁共振成像扫描，其中S组19人，L组18人，两组被试年龄、性别、人格、焦虑和抑郁状态都没有显著差异；使用SPM5软件对脑成像数据进行预处理，之后使用静息态功能磁共振数据分析软件包（REST）软件进行局部一致性、低频振幅和功能连接的分析，用双样本t检验对两组不同基因型被试的杏仁核、内侧前额叶皮层以及其它情感相关脑区的活动情况进行比较。【研究结果】对不同基因型被试静息状态时的脑成像数据进行处理，使用双样本t检验进行比较：1、 局部一致性的方法发现：（1）L等位基因纯合子个体其杏仁核的活动高于S等位基因纯合子个体（p﹤0.05）；（2）性别分组研究发现，对女性被试，其L等位基因纯合子个体杏仁核的活动高于S等位基因纯合子个体（p﹤0.05），而腹内侧前额叶皮层的活动低于S等位基因纯合子个体（p﹤0.05），而不同基因型的男性被试其杏仁核和腹内侧前额叶皮层的活动均无显著差异；2、 使用低频振幅的方法，对两组不同基因型被试的杏仁核和腹内侧前额叶皮层的活动情况进行比较，均未见显著差异；3、 使用功能连接的方法，对两组不同基因型被试的双侧杏仁核和腹内侧前额叶皮层的连接强度进行比较，未见显著差异。【研究结论】1、 五羟色胺转运体基因的多态性影响个体杏仁核和腹内侧前额叶皮层等情感相关脑区的自发活动，这预示着五羟色胺转运体基因的多态性与情感障碍（如抑郁症）对应的脑功能有关，但是这种差异可能受种族差异的影响； 2、 五羟色胺转运体基因对情感相关脑区的自发活动的影响存在性别差异，这种差异可以部分解释男女在相同压力条件下患情感障碍概率的差异，也进一步提示遗传对情感相关脑区的活动的作用受性别的影响； 3、 局部一致性作为对静息态功能磁共振数据的一种分析指标，能够敏感地反应情感相关脑区活动的个体差异。关键词：静息态功能磁共振成像，五羟色胺转运体基因，杏仁核，腹内侧前额叶皮层，局部一致性，低频振幅

5-HTTLPR POLYMORPHISM IMPACTS SPONTANEOUS BRAIN FUNCTION IN CHINESE COLLEGE STUDENTSABSTRACT[BANKGROUND]A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety. Recent advances in integrating noninvasive functional neuroimaging with genetics have demonstrated an association of 5-HTTLPR genotype with amygdala and ventro-media prefrontal cortex (VMPFC) function in the healthy human brain during the processing of negative stimuli. Compared with the homozygous for the 5-HTTLPR long allele (L/L) group, the homozygous for the 5-HTTLPR short allele (S/S) group showed greater amygdala neuronal activity and smaller VMPFC neuronal activity. It demonstrated that 5-HTTLPR genotype can alter human behavior and performance by changing brain function of emotion-related regions in emotion processing. However, there is little study to investigate the relationship between the 5-HTTLPR genotype and brain spontaneous activity. The different response in emotion-related regions may due to the discrepancy of spontaneous brain activity. [OBJECTIVES]1. To explore the different response in the amygdala and VMPFC which are related to emotion between different 5-HTTLPR genotypes.2. To explore whether the relationship between 5-HTTLPR genotype and brain activity was mediated by gender.[METHODS]Thirty-seven right-handed subjects participated in this study, nineteen in the S/S group and eighteen in the L/L group, underwent BOLD functional magnetic resonance imaging (fMRI) during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. Resting fMRI data were preprocessed with SPM5 and analyzed with regional homogeneity (ReHo) and amplitude of low frequency fluctuation (ALFF) and functional conectivity by the REST software. Using two sample t-test to compare the two genotype groups by selecting regions of interest (ROI), such as amygdala and ventromedial prefrontal cortex.[RESULTS]After processing the fMRI data of two different groups, two sample t test showed the following results.1. By using the ReHo analysis, we found that: (1) Compared with the L/L group, the S/S group showed significantly decreased activity in the amygdala; (2) In female, the S/S group showed significantly decreased activity in the amygdala and increased activity in the ventromedial prefrontal cortex, while there was no such difference. 2. ALFF analysis didn’t show significant difference in the amygdala and VMPFC.3. Functional connectivity between amygdala and VMPFC didn’t show any significant difference. [CONCLUSIONS]1. 5-HTTLPR genotype can alter the spontaneous brain activity in the amygdala and VMPFC, which are related with emotion. It suggests that there is a correlation between 5-HTTLPR genotype and spontaneous brain activity. And the correlation is mediated by ethnic differences.2. The relationship between 5-HTTLPR genotype and spontaneous brain activity is affected by gender, which partly accounted for the gender difference of probability with affective disorder.3. As an index to measure the resting brain activity, ReHo can explore and evaluate the functional impact of brain-relevant genetic polymorphisms more rapidly and with greater sensitivity than ALFF. KEY WORDS：resting-state fMRI, 5-HTTLPR, amygdala, VMPFC, ReHo, ALFF