Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling
Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling
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DOI：
10.1017/s0033291713003231
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发表时间：
2014-08-01
影响因子：
6.9
通讯作者：
Binder, E. B.
中科院分区：
文献类型：
--
作者：
Mehta, D.;Newport, D. J.;Binder, E. B.
背景产后抑郁症（PPD）影响约13%的妇女，并对母亲和婴儿产生负面影响，因此早期发现PPD的可靠生物学测试至关重要。我们的目的是在一项无假设的全基因组研究中，在一个高风险的纵向队列中，使用外周血基因表达谱来确定PPD的可靠预测生物标志物。我们进行了一项全基因组关联研究，在纵向发现队列包括62名妇女与精神病理学。在第一和第三个怀孕三个月和产后早期（201个样本）的基因表达和激素进行了测量。复制队列包括24名妇女与孕晚期基因表达措施。在Illumina-Human HT 12 v4微阵列上测量基因表达。测定血浆雌二醇和雌三醇。在R.结果中进行统计分析。我们确定了116个转录差异表达之间的PPD和正常的妇女在妊娠晚期，允许预测PPD的准确性为88%的发现和复制队列。在这些转录本中，转录本的显著富集暗示观察到雌激素信号传导，并且当分析预测来自非风险队列的PPD的已发表基因表达数据时，这种富集也是明显的。虽然血浆雌激素水平在各组之间没有差异，但PPD患者对雌激素信号的敏感性增加，证实了先前提出的性类固醇敏感性增加是PPD易感因素的假设。这些结果表明，PPD可以稳健地预测在目前的正常女性早在孕晚期，这些研究结果具有预测性测试的高风险妇女和预防和治疗PPD的影响。
Background. Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort.Method. We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R.Results. We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD.Conclusions. These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.