Perinatal Depression & Anxiety: Relationships with Late Pregnancy Thyroid Status

描述（由申请人提供）：高达30%的产后妇女出现抑郁症状，14%出现严重或轻微的抑郁症。虽然甲状腺状态和抑郁之间的关系在一般人群中已经确立，并且在怀孕期间和之后会发生较大的甲状腺变化，但很少有关于产前或产后（围产期）抑郁中甲状腺功能的研究。我们发现妊娠后期甲状腺总和游离甲状腺素（TT4, FT4）浓度较低和围产期抑郁自我评分较高之间存在显著相关性。抑郁程度低的母亲产后TSH水平明显下降，但没有下降，而抑郁程度高的母亲产后TSH水平明显升高。有抑郁史的母亲产前TT4和FT4浓度较低的比例显著较高。我们将在一个更大的队列（N = 200）中检验我们发现的有效性，确定较低的妊娠后期TT4和FT4水平是否也与围产期综合征（严重或轻微）抑郁或焦虑症状或障碍有关，确定较低的孕前TT4和FT4水平是否与抑郁史有关，并测试产前甲状腺测量是否能改善产后抑郁症的预测，特别是在与已知的危险因素(虐待史、压力生活事件、低社会支持)。我们假设围产期抑郁与性激素对HPT轴的抑制更敏感有关，也可能与怀孕期间皮质醇升高导致产前TT4和FT4水平降低有关。这导致在产后这些激素水平迅速下降后，HPT轴的中央驱动激增，从而产生更高的产后TSH水平。HPT轴中央驱动增强的指标（脑脊液TRH浓度升高，TRH抑制TSH释放）与重度抑郁症相关。为了验证我们的理论，我们将确定较低的产前TT4和FT4水平是否与较高的产后TSH水平显著相关，以及这种关系是否与围产期抑郁症有关。我们还将研究妊娠晚期性激素和皮质醇水平与妊娠晚期TT4和FT4水平之间是否存在相互作用，以预测围产期抑郁症。公共卫生相关性：大约14%的母亲在分娩后的头3个月内出现临床抑郁症，在怀孕期间出现抑郁症的比例相似。该项目基于两项初步研究，发现产后抑郁的母亲在怀孕后期甲状腺激素水平相对较低（但在正常范围内），但在分娩后其他甲状腺激素水平较高。这个项目的目标是看看这些结果是否在更多的孕妇和产后妇女中得到证实，怀孕后期的甲状腺激素水平是否有助于预测哪些母亲会变得抑郁，产前或产后甲状腺测量是否与焦虑症状或障碍有关（这在产后时期也很常见），以及测试一个关于怀孕后期甲状腺激素水平较低如何导致产后抑郁症的理论。

DESCRIPTION (provided by applicant): Up to 30 percent of postpartum women develop depressive symptoms and 14% develop major or minor depression. Although relationships between thyroid status and depression are well established in the general population and large thyroid changes occur during and following pregnancy, there have been few studies of thyroid function in pre or postpartum (perinatal) depression. We found robustly significant correlations between low, euthyroid range total and free thyroxine (TT4, FT4) concentrations during late pregnancy and higher perinatal depression self-ratings. Postpartum TSH levels fell significantly in mothers with low depression but did not decline and were significantly more elevated in mothers who were more depressed. A significantly higher fraction of mothers with depression history had lower prepartum TT4 & FT4 concentrations. We will test the validity of our findings in a larger cohort (N = 200), determine if lower late pregnancy TT4 & FT4 levels are also related to perinatal syndromal (major or minor) depression or anxiety symptoms or disorders, ascertain whether lower prepartum TT4 & FT4 levels are related to depression history and test whether prenatal thyroid measures improve prediction of postpartum depression especially when combined with known risk factors (abuse history, stressful life events, low social support). We hypothesize that perinatal depression is related to greater sensitivity to suppression of the HPT axis by sex hormone and possibly cortisol elevations during pregnancy producing lower prepartum TT4 & FT4 levels. This results in a surge of central drive in the HPT axis after the rapid postpartum drop in these hormone levels producing higher postpartum TSH levels. Indices of increased central drive in the HPT axis (elevated CSF TRH concentrations, blunted TSH release by TRH) are associated with major depression. To test our theory, we will determine if lower antenatal TT4 & FT4 levels are significantly related to higher postpartum TSH levels and if that relationship is associated with perinatal depression. We will also examine if there are interactions between late pregnancy sex hormone and cortisol levels and late pregnancy TT4 & FT4 levels in predicting perinatal depression. PUBLIC HEALTH RELEVANCE: About 14% of mothers develop clinical depression within the first 3 months after giving birth and a similar percentage become depressed during pregnancy. This project is based on two preliminary studies that found that mothers who are more depressed postpartum have relatively low (but normal range) thyroid hormone levels during late pregnancy but then have higher levels of other thyroid hormones after giving birth. The goals of this project are to see if these results are confirmed in a much larger number of pregnant and postpartum women, if thyroid hormone levels during late pregnancy might help predict which mothers will become depressed, if pre or postpartum thyroid measures are related to anxiety symptoms or disorders (which are also common in the postpartum period) and to test a theory about how lower late pregnancy thyroid hormone levels might contribute to postpartum depression.