Perinatal Depression & Anxiety: Relationships with Late Pregnancy Thyroid Status

描述(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。尽管在一般人群中甲状腺状态与抑郁症之间的关系已经确立，并且在怀孕期间和之后会发生甲状腺的巨大变化，但关于产前或产后(围产期)抑郁症的甲状腺功能的研究还很少。我们发现妊娠晚期低、正常甲状腺范围总甲状腺激素和游离甲状腺激素(TT4、FT4)浓度与较高的围产期抑郁自评显著相关。产后TSH水平在抑郁程度较低的母亲中显著下降，但没有下降，而在抑郁程度较高的母亲中明显升高。有抑郁症病史的母亲产前TT4和FT4浓度较低的比例明显较高。我们将在更大的队列(N=200)中测试我们的发现的有效性，确定较低的妊娠晚期TT4和FT4水平是否也与围产期综合征(主要或轻微)抑郁或焦虑症状或障碍有关，确定较低的产前TT4和FT4水平是否与抑郁史有关，并测试产前甲状腺指标是否改善产后抑郁的预测，特别是在结合已知的危险因素(虐待史、应激性生活事件、低社会支持)时。我们假设，围产期抑郁与性激素对HPT轴的抑制更敏感有关，可能在妊娠期间皮质醇升高，导致产前TT4和FT4水平较低。这导致在产后这些激素水平迅速下降后，HPT轴的中枢驱动激增，产生更高的产后TSH水平。HPT轴中心驱动力增强的指标(脑脊液TRH浓度升高，TRH钝化TSH释放)与重度抑郁症相关。为了验证我们的理论，我们将确定产前较低的TT4和FT4水平是否与产后较高的TSH水平显著相关，以及这种关系是否与围产期抑郁有关。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水平在预测围产期抑郁方面是否存在交互作用。与公共卫生相关：大约14%的母亲在分娩后的前3个月内患上临床抑郁症，类似比例的母亲在怀孕期间抑郁。该项目基于两项初步研究，这两项研究发现，产后抑郁程度较高的母亲在怀孕后期甲状腺激素水平相对较低(但范围正常)，但在分娩后其他甲状腺激素水平较高。该项目的目标是看看这些结果是否在更多的怀孕和产后女性中得到证实，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，产前或产后的甲状腺指标是否与焦虑症状或障碍(产后时期也很常见)有关，并测试关于妊娠晚期甲状腺激素水平较低可能导致产后抑郁的理论。

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.