Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi
Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi
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DOI：
10.1038/tp.2015.32
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发表时间：
2015-04-07
影响因子：
6.8
通讯作者：
Szyf, M.
中科院分区：
文献类型：
--
作者：
Nemoda, Z.;Massart, R.;Szyf, M.
抑郁症影响到10-15%的孕妇，并与早产以及后来的发育、行为和学习障碍有关。我们验证了母亲抑郁与母亲T淋巴细胞、新生儿脐带血T淋巴细胞和成年后代海马的DNA甲基化改变有关的假设。应用Illumina甲基化450 K芯片分析了38例产前产妇和44例新生儿脐带血样本中CD3+ T淋巴细胞的全基因组DNA甲基化。先前获得的甲基化数据集使用甲基化DNA免疫沉淀和阵列杂交的62个死后成年男性海马样本进行重新分析，以测试与母亲抑郁史的关联。我们发现，与对照组相比，母亲抑郁组新生儿脐带血T淋巴细胞中有145个（FDR q < 0.05）和2520个（FDR q < 0.1）位点甲基化差异。然而，在我们的初步数据集中，产前母体T淋巴细胞中没有检测到显著的DNA甲基化差异。我们还在与母亲抑郁史相关的海马样本中检测到294个差异甲基化探针（FDR q < 0.1）。我们观察到33个基因的显著重叠（P = 0.002）与新生儿和成年后代大脑T淋巴细胞DNA甲基化的变化有关。这些基因中有许多与免疫系统功能有关。我们的研究结果表明，与母亲抑郁症相关的后代的DNA甲基化变化在出生时就可以在免疫系统中检测到，并在大脑中持续到成年。这与一种假设是一致的，即全系统的表观遗传变化涉及后代对母亲抑郁的终身反应。
Depression affects 10-15% of pregnant women and has been associated with preterm delivery and later developmental, behavioural and learning disabilities. We tested the hypothesis that maternal depression is associated with DNA methylation alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes isolated from 38 antepartum maternal and 44 neonatal cord blood samples were analyzed using Illumina Methylation 450 K microarrays. Previously obtained methylation data sets using methylated DNA immunoprecipitation and array-hybridization of 62 postmortem hippocampal samples of adult males were re-analyzed to test associations with history of maternal depression. We found 145 (false discovery rate (FDR) q < 0.05) and 2520 (FDR q < 0.1) differentially methylated CG-sites in cord blood T lymphocytes of neonates from the maternal depression group as compared with the control group. However, no significant DNA methylation differences were detected in the antepartum maternal T lymphocytes of our preliminary data set. We also detected 294 differentially methylated probes (FDR q < 0.1) in hippocampal samples associated with history of maternal depression. We observed a significant overlap (P = 0.002) of 33 genes with changes in DNA methylation in T lymphocytes of neonates and brains of adult offspring. Many of these genes are involved in immune system functions. Our results show that DNA methylation changes in offspring associated with maternal depression are detectable at birth in the immune system and persist to adulthood in the brain. This is consistent with the hypothesis that system-wide epigenetic changes are involved in life-long responses to maternal depression in the offspring.