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Alternative TitleThe Recent Progress in the Research on Association Between 5-HTTLPR and Depression
张俊先1; 陈杰1; 李新影1
Source Publication心理科学
Contribution Rank2
Other AbstractIn recent years, a great number of studies have demonstrated the interacting effect between 5-HTTLPR, a length polymorphism in the serotonin transporter gene, and environmental adversity on depression. This review systematically discussed researches on the association between 5-HTTLPR and depression, and 5-HTTLPR×Environment interaction. Neuroimaging and neuroendocrinological studies examining the mechanisms underlying the 5-HTTLPR×Stress interaction and the Gene×Gene×Environment interactions were further discussed. In this review, we began with association studies linking 5-HTTLPR genotype and depression in both animal models and human studies. Although the reported 5-HTTLPR×Environment interaction was followed by a number of replications, several large studies, however, showed inconsistent results. We found that this discrepancy in results could partly be explained by the different sex and age composition of different samples. For example, the S/S genotype might increase an individual’s susceptibility to depression under stressful conditions only in females, not in males. Data based on adolescent and elderly samples often led to negative results. We then discussed the mechanisms underlying 5-HTTLPR×Stress interaction on depression. First, in neuroimaging studies, S allele was found to influence the activity of amygdala, a brain region being central to the neural circuitry mediating emotional arousal and vigilance across species. S allele carriers exhibited greater amygdala activity than L allele homozygotes. Studies also found that the gray matter volume in a specific region of the PFC, the perigenual anterior cingulate cortex (pACC), was significantly reduced in S allele carriers as compared with L allele homozygotes. Moreover, fMRI analysis of relative activation of the pACC and amygdala during presentation of angry and fearful faces revealed a relatively weaker functional coupling between these regions in the S allele carriers. These findings suggested that 5-HTTLPR might influence the emotion-processing brain region and circuits, thus, rendering the liability to depression. Second, findings from psychophysiological studies suggested that another possible mechanism involved the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress for S/S carriers. When confronted with stressful life events, individuals with S/S genotype might be at a greater risk for depression due to heightened cortisol exposure. There were also situtations in which the 5-HTTLPR×Environment interaction was further subjected to the influence of other genes. We then speculated the possibility of epistatic effects and Gene×Gene×Environment interactions. CYP2C9 gene and BDNF gene emerged as two candidates for epistasis effects with 5-HTTLPR. Individuals carrying both S and CYP2CY*3 alleles were found to be at a greater risk of suffering depression. Studies also found significant a three-way interaction between 5-HTTLPR, BDNF, and childhood maltreatment in predicting the risk of depression. Finally, future directions were suggested. We anticipated the combination of research approach of genetics, animal models, neruoimaging and neuroendorinology to explore the more detailed mechanisms underlying 5-HTTLPR×Stress interaction in depression.
Keyword5-HTTLPR 抑郁 交互作用 生活事件 机制
Subject Area医学心理学
Indexed ByCSCD
Funding Organization本研究得到国家自然科学基金(30600183)、中国科学院心理研究所创新项目(KX05-066)和中国科学院心理研究所青年基金(07CX071007)资助.
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Document Type期刊论文
Corresponding Author李新影
Recommended Citation
GB/T 7714
张俊先,陈杰,李新影. 5-HTTLPR与抑郁相关性的研究动态[J]. 心理科学,2012,35(1):226-232.
APA 张俊先,陈杰,&李新影.(2012).5-HTTLPR与抑郁相关性的研究动态.心理科学,35(1),226-232.
MLA 张俊先,et al."5-HTTLPR与抑郁相关性的研究动态".心理科学 35.1(2012):226-232.
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