Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
J Affect Disord. 2009 Dec;119(1-3):107-15. doi: 10.1016/j.jad.2009.02.023. Epub 2009 Mar 31.
A polymorphism in the serotonin transporter (5-HTT) gene seems to moderate the influence of stressful life events on depression. However, the results from previous studies of gene-environment interactions in depression are inconsistent and might be confounded by the history of depression among participants.
We applied a case-only design, including 290 ethnically homogeneous patients suffering exclusively from first episode depression. Psychiatric mo-morbidity, personality traits and disorders and stressful life events in a six months period preceding onset of depression were evaluated by means of interviews and questionnaires. Additionally, we genotyped nine polymorphisms in the genes encoding the serotonin transporter, brain derived neurotrophic factor, catechol-O-methyltransferase, angiotensin converting enzyme, tryptophane hydroxylase, and the serotonin receptors 1A, 2A, and 2C.
The low activity variants of the 5-HTT-linked polymorphic region in the serotonin transporter gene and the Met-allele of a single nucleotide polymorphism (Val66Met) in the gene encoding brain derived neurotrophic factor were independently associated with the presence of stressful life events prior to onset of depression, also when corrected for the effect of age, gender, marital status, personality disorder, neuroticism, and severity of depressive symptoms at the time of interview.
Polymorphisms in the genes encoding the serotonin transporter and the brain derived neurotrophic factor interact with recent stressful life events on depression among patients with no history of previous depressive episodes.
5-羟色胺转运体（5-HTT）基因的多态性似乎可以调节生活应激事件对抑郁的影响。然而，之前关于抑郁的基因-环境相互作用的研究结果并不一致，并且可能受到参与者的抑郁史的干扰。
我们应用了病例对照设计，包括 290 名患有首发抑郁症的同一种族同质患者。通过访谈和问卷调查评估了发病前 6 个月内的精神科共病、人格特征和障碍以及生活应激事件。此外，我们对编码 5-羟色胺转运体、脑源性神经营养因子、儿茶酚-O-甲基转移酶、血管紧张素转换酶、色氨酸羟化酶以及 5-羟色胺受体 1A、2A 和 2C 的基因中的 9 个多态性进行了基因分型。
5-羟色胺转运体基因中的 5-HTT 连锁多态区的低活性变体和脑源性神经营养因子基因中的单核苷酸多态性（Val66Met）的 Met 等位基因与抑郁发作前生活应激事件的发生独立相关，即使在考虑了年龄、性别、婚姻状况、人格障碍、神经质和访谈时抑郁症状严重程度的影响后也是如此。
在没有既往抑郁发作史的患者中，编码 5-羟色胺转运体和脑源性神经营养因子的基因多态性与近期生活应激事件相互作用，导致抑郁。
