基因检测可用于妇女产后抑郁症风险的鉴定
2012-05-19 12:17:19   来源： 丁香园   作者：  评论：0 点击：

基因测试可使女性在确诊产后抑郁症之前就知道自己发生该病的风险

Florence, Italy: British researchers have discovered a way of identifying which women are most at risk of postnatal depression (PND). The findings could lead to the development of a simple, accurate blood test for the likelihood of any individual developing the condition, they say.

在意大利佛罗伦萨，英国研究人员已经发现了一种方法来识别哪些妇女患产后抑郁症的风险最高。他们说这一方法可以用来开发一个简单而准确的血液测试来筛查有可能患产后抑郁症的妇女。

Presenting the research to the International Congress of Endocrinology/European Congress of Endocrinology today (7 May 2012) Professor Dimitris Grammatopoulos, Professor of Molecular Medicine at the University of Warwick, Coventry, UK, said that approximately one in seven women who give birth suffer from PND, which normally starts around two weeks after childbirth. PND can have serious long-term repercussions both on family life and in the emotional and cognitive development of the baby.

来 自于英国考文垂（Coventry）Warwick大学的医学分子学教授Dimitris Grammatopoulos于今天(2012年5月7日)向国际内分泌会议暨欧洲内分泌会议提交了该研究，他说大约有七分之一的女性在生产后会患上产后 抑郁症,PND通常开始于分娩后的两个星期内。产后抑郁症可长期严重地影响家庭生活和正处于情感和认知发展期的婴儿。

“Current screening policies rely on the opportunistic finding of PND cases, and screening tools such as the Edinburgh Postnatal Depression Score (EPDS)[1] cannot identify women at risk prospectively,” he said. “We think that we have made an important step forward in characterising the prospective risks and therefore paving the way for timely, appropriate medical treatment for women who are likely to develop PND.”

Dimitris Grammatopoulos教授还说，目前的筛查只能碰巧发现患产后抑郁症的病例,筛查工具如爱丁堡产后抑郁评分(EPDS)[1]不能预测妇女患产后抑郁症的风险，我们已经在预测妇女未来患产后抑郁症的风险上向前迈出了一大步，因此对有可能患上产后抑郁症的妇女可以及时而适当的进行医疗干预。”

The researchers assessed a group of 200 pregnant women for PND using the EPDS, once at the time of recruitment to the trial (first visit to the ante-natal clinic) and again two to eight weeks after they had given birth. They found that the women who developed PND were more likely to have specific genetic variants of the bcl1 and rs242939 single nucleotide polymorphisms (SNPs)[2] of the glucocorticoid receptor and the corticotrophin-releasing hormone receptor-1 genes, respectively.

研究人员用爱丁堡产后抑郁评分(EPDS)为200名孕妇评估患产后抑郁症的风险，分别在入组到该试验时(第一次到访产前诊所)和分娩后两至八个星期进行两次评估。他们发现患产后抑郁症的妇女可能在糖皮质激素受体的bcl1和促肾上腺皮质激素释放激素受体-1的rs242939单核苷酸多态性(SNPs)[2]有特定的基因变异。

These receptors control the activity of the hypothalamo-pituitary adrenal (HPA) axis, an endocrine system that is activated in response to stress. The hypothalamus is part of the brain that monitors many aspects of the state of the body?s systems and is closely linked with the pituitary gland, which releases a number of hormones into the blood stream that control vital body functions.

这些受体可以控制下丘脑-垂体-肾上腺(HPA)轴的活性,HPA轴是一个对应激产生反应的内分泌系统。下丘脑是大脑的一部分，它可以控制人类身体许多系统的状态并与脑垂体紧密联系，释放大量的荷尔蒙到血液中从而控制至关重要的身体功能。

The finding appears to show that postnatal depression is a specific subgroup of depression with a distinct genetic element which means that some women are genetically more reactive to the environment, and that pregnancy may be a trigger factor for depression, the researchers say.

研究人员说，这一发现似乎表明产后抑郁症是一种与独特的基因元素相关的抑郁症亚型，这意味着一些女性在病因上相比环境而言对遗传更敏感，而怀孕可能是抑郁症的触发因素。

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“Although we knew already that there was an association of the HPA axis with depression, ours is the first study to show a link between specific elements of this pathway and the particular case of PND,” said Professor Grammatopoulos. “We now intend to conduct further research on other genetic variants of the HPA axis in a larger, multi-centre study involving women from Coventry, Birmingham, and London.”

Grammatopoulos 教授说，“虽然我们早已知道下丘脑-垂体-肾上腺(HPA)轴与抑郁症相关，我们的研究首次展示了特定基因受体影响HPA轴从而导致产后抑郁症之间的联 系”，“我们现在打算在考文垂、伯明翰、和伦敦进行更大的多中心临床研究开来进一步探索肾上腺皮质轴的其他遗传变异的基因。”

PND is a serious condition, the researchers say, and quite different from the ?baby blues?, which is milder and shorter-lived. Symptoms include sadness, changes in eating and sleeping patterns, crying episodes, reduced libido, anxiety and irritability.

研究人员说产后抑郁症是一种严重的疾病，症状包括悲伤、饮食变化、睡眠模式改变、发作性哭泣、性欲降低、焦虑和易怒。它与产后情绪低落（baby blues）有很大的不同，后者相对抑郁程度轻且持续时间也短。

Effects on children can be significant; for example, depressed mothers are less likely to be affectionate towards and to play with their children and they may use less ?baby talk? which is designed to engage the child?s attention. This may lead to learning and emotional difficulties for the children in later life.

产后抑郁症对孩子的影响是明显的，例如，患抑郁症的妈妈不太可能温柔的对待和陪孩子玩，她们会较少对孩子说儿语（baby talk）而这能很好的引起孩子们的注意。最终将导致孩子在以后的人生里可能有学习和情感的困难。

Although it may seem evident that PND is caused by some kind of hormonal upheaval, some clinicians still believe that it could be due to birth trauma, and the role of the HPA axis in this form of depression has not been proved until now. “We believe that we have made a discovery with important clinical and social implications. If we can identify women likely to suffer from PND in advance so that they can be treated appropriately and at an early stage, we will have improved the lives not just of the parents, but also of their children,” Professor Grammatopoulos concluded.

尽管患产后抑郁症很明显是由于某种激素变化所致,一些临床医生仍然相信这可能是由于 分娩创伤所致，HPA轴对抑郁症发生的作用直到现在还未得到证明。Grammatopoulos教授得出结论，“我们相信我们已经有了一个对临床和社会有 重大意义的发现。如果我们能提前确定妇女可能患有产后抑郁症的风险，她们就可以在早期就得到妥善的治疗，而早期治疗将不仅改善父母的生活，还能帮助他们的 孩子。”

ABSTRACT摘要

Genetic variation of the hypothalamo-pituitary axis may increase susceptibility of postnatal depression

下丘脑-垂体-肾上腺(HPA)轴的遗传变异会增加产后抑郁症的易感性

N. Engineer1, L. Darwin1, N. Deole1, K. Ngianga-Bakwin2, S. Smith1 & D. Grammatopoulos1,2 1University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK; 2University of Warwick, Coventry, UK.

Objective: To investigate whether genetic variants in the glucocorticoid receptor (GR) and corticotropin releasing hormone receptor 1(CRHR1) genes are associated with increased susceptibility for postnatal depression (PND).

目的：探讨是否在糖皮质激素受体(GR)和促肾上腺皮质激素释放激素受体1(CRHR1)的基因可增加产后抑郁症的易感性。

Methods: A prospective longitudinal cohort study at University Hospital, Coventry, England. Two hundred pregnant women were recruited and assessed for PND using the Edinburgh Postnatal Depression Score (EPDS) upon recruitment and again 2-8 weeks post-natally. Five SNPs with established association to depression were genotyped. Association analysis was carried out in 140 patients that completed the study protocol.

方法：来自于英格兰考文垂大学医院的前瞻性纵向队列研究，入组了200位孕妇并用爱丁堡产后抑郁评分(EPDS)来为200名孕妇评估患产后抑郁症的风险，分别在入组到该试验时(第一次到访产前诊所)和分娩后两至八个星期进行两次评估。基因分型研究发现5个基因的单核苷酸多态性（SNPs ）与抑郁症有联系，对完成该研究的140个病人进行了这5个基因的关联分析。

Results: The bcl1 SNP of the GR and rs242939 SNP of the CRHR1 genes were over-represented in women with PND with significant allele association. Risk ratios for development of PND associated with presence of each minor allele were 2.9(95% confidence interval: 1.2 to 6.9) for bcl1 and 4.9(2 to 12) for rs242939. In contrast, no significant association was found between PND and the R23K, rs1876828 or rs242941 SNPs.

结果：糖皮质激素受体(GR)的bcl1 SNP和促肾上腺皮质激素释放激素受体1(CRHR1)的rs242939 SNP在女性产后抑郁症有显著的等位基因高表达。bcl1与患产后抑郁症的风险率是2.9(95%置信区间是1.2 - 6.9)，rs242939 是4.9(95%置信区间是2 - 12)。相比之下，产后抑郁症和R23K,rs1876828和rs242941的SNPs没有发现明显的相关关系。

Conclusions: This is the first demonstration that specific SNPs of the GR and CRHR1 genes are associated with PND and might represent promising genetic biomarkers to help early identification of women at risk of PND.

结论:该实验是首个研究能证明特定的糖皮质激素受体(GR)和促肾上腺皮质激素释放激素受体1(CRHR1)的单核苷酸多态性（SNPs）与产后抑郁症有相关性并可能成为有前景的基因标志物来帮助早期筛查产后抑郁症风险。