Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression.
Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression.
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DOI：
10.1176/ajp.2006.163.9.1588
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发表时间：
2006-09
期刊：
影响因子：
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通讯作者：
G. Zalsman;Yung-yu Huang;M. Oquendo;A. Burke;Xian-zhang Hu;D. Brent;S. Ellis;D. Goldman;J. Mann-J
中科院分区：
文献类型：
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作者：
G. Zalsman;Yung-yu Huang;M. Oquendo;A. Burke;Xian-zhang Hu;D. Brent;S. Ellis;D. Goldman;J. Mann-J
目的研究5-羟色胺转运基因5′启动子区（5- httlpr）多态性的低表达等位基因与应激性生活事件的抑郁和自杀易感性相关。作者研究了5-HTTLPR试验等位基因多态性与生活压力事件、重度抑郁症的严重程度和自杀倾向的关系。方法对191名情绪障碍受试者和125名健康受试者进行三等位基因5-HTTLPR多态性基因分型(高表达等位基因L(A)；低表达等位基因：L(G)， S)。所有受试者都接受了结构化的临床访谈，以确定DSM-IV诊断、精神病理学评分、生活压力事件、发展史和自杀行为。在一个亚组中检测CSF 5-HIAA。结果与高表达的L(A)等位基因相比，低表达的等位基因独立预测更严重的抑郁严重程度，并预测中度至重度生活事件中更严重的重度抑郁症。自杀行为与脑脊液5-HIAA无关联。结论：低表达的转运体等位基因，直接或通过增加应激生活事件对严重程度的影响，解释了31%的重度抑郁症严重程度差异。造成这些影响的生物学表型仍有待阐明。
OBJECTIVE The lower expressing allele of the serotonin transporter gene 5' promoter region (5-HTTLPR) polymorphism is reported to be associated with susceptibility to depression and suicidality in response to stressful life events. The authors examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events, severity of major depression, and suicidality. METHOD Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasian subjects of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism (higher expressing allele: L(A); lower expressing alleles: L(G), S). All subjects underwent structured clinical interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed in a subgroup of subjects. RESULTS Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate to severe life events compared with the higher expressing L(A) allele. No associations with suicidal behavior and CSF 5-HIAA were found. CONCLUSIONS Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated.