产后抑郁症和分娩疼痛的关联及其神经生物学机制的研究

Postpartum depression (PPD) is a common psychological and behavioral disorder in puerperium, which is characterized by long lasting blue mood, while in severe cases it may be accompanied by hallucination and suicide. The prevalence of PPD in China is about 15%-30%. PPD not only affects the recovery of the mother and her performance, but also negatively impacts the development of infant's emotion, intelligence and behavior. It is thus a potential public health problem that critically affects the national economy and social development. Our previous small-sample study found that the incidence of PPD in analgesia + dola group which had good analgesic effect was significantly lower than those whom had poor analgesic effect, meanwhile we also found blood stress hormones（CRH, OFQ） in women whom had good analgesic effect in labour was significantly lower than those women who didn't have good analgesic effect. Therefore, We propose a scientific hypothesis on the mechanism that genetic polymorphisms, labour pain, together with the neuroactive compounds involved are the key factors which cause the PPD. In the present project we will perform a double-blind randomized clinical study with a large sample size to observe the influence of labor analgesia on the incidence of PPD, analyze the change of related neurotransmitter in depressives and nondepressives and elucidate the correlation between the labour pain and PPD in Chinese women and its potential mechanism.We aim to provide scientific evidence that will enable prevention and rational treatment of PPD.

产后抑郁症（PPD）是产褥期常见的心理行为异常，以情感持续低落为特征，重者出现幻觉甚至自杀等症状。我国 PPD 的发生率高达 15%-30%，不仅影响产妇的产褥期康复及履行母亲职责，而且对于婴幼儿情绪、智力发育和行为发展等存在严重影响，是严重影响国民经济和社会发展的公共卫生问题。我们前期的小样本调查发现分娩时镇痛效果确切的产妇抑郁症发生率显著低于镇痛效果差的产妇，同时发现分娩镇痛效果确切的产妇血中一些抑郁症相关应激激素（CRH，OFQ）显著低于镇痛不确切者。因此我们推测：产妇的遗传学易感性、分娩疼痛及其所关联的神经活性物质改变可能是导致 PPD 发生的关键因素。本课题将采用部分随机双盲对照大样本临床研究，观察分娩镇痛对抑郁症发生率的影响，分析抑郁症者和非抑郁症者相关神经介质的变化，揭示分娩疼痛和 PPD 之间的关联性及其可能的机制。为PPD的防治策略提供科学依据。

1.研究背景.产后抑郁症（PPD）是产褥期常见的心理行为异常，以情感持续低落为特征，重者出现幻觉甚至自杀等症状。我国 PPD 的发生率高达 15%-30%，不仅影响产妇的产褥期康复及履行母亲职责，而且对于婴幼儿情绪、智力发育和行为发展等存在严重影响，是严重影响国民经济和社会发展的公共卫生问题。.2.主要研究内容.（1）采用随机双盲对照大样本量临床研究，进行分娩疼痛和 PPD 的临床流行性病学调查.（2）分娩疼痛和 PPD 的相关神经生物学关键活性物质研究.（3）关键基因多态性研究.3.重要结果及关键数据.（1）本研究共收集673名产妇，样本共流失108例，最后入组565例；其中单纯导乐组n=301例，导乐+经皮电神经（TENS）组n=51例，导乐+硬膜外麻醉组n=213例，之后产后随访得出的结论，产后2-4周，发现总产后抑郁率为10.62%，其中单纯导乐组，导乐+ TENS组以及导乐+硬膜外麻醉组的产后抑郁率分别为7.37%、7.88%和16.97%。经过数据分析，在实施分娩镇痛前后，疼痛评分可以看出，VAS评分除镇痛前，其他各时点均存在明显统计学差异；硬膜外麻醉组减少分娩疼痛程度最佳，TENS次之，其次为导乐组。.（2）完成分娩镇痛和PPD相关神经活性物质的测定，由于经费限制，共完成167例，其中单纯导乐组42例，TENS组50例，硬膜外麻醉组75例。经过数据分析，发现如下结果：.CRF水平在宫口开到3cm时，组间存在统计学差异p=0.006；BDNF与OFQ水平在各时间点均存在统计学差异p＜0.0001；5HT在镇痛前及宫口开全时，组间有统计学差异p＜0.0001.4.科学意义.（1）硬膜外麻醉药物分娩镇痛并不能降低产后抑郁发生风险，而产时合理的陪伴可能缓解孕产妇产时焦虑，从而降低产后抑郁的发生风险。而硬膜外麻的镇痛效果较其他两种非药物镇痛效果显著，可明显缓解分娩疼痛，TENS作为物理镇痛方法，虽分娩镇痛效果不及药物性镇痛效果明显，但能适度缓解分娩镇痛效果。.（2）本研究显示，硬膜外麻醉组在4个时点的OFQ水平均比其他两组要高；TENS组在4个时点的CRF水平均比其他两组要高。OXT水平在硬膜外麻醉组显著降低，5-HT水平在TENS组显著降低，BDNF水平在导乐组显著降低。