Department of Psychiatry and Psychotherapy, University Hospital Tübingen, Calwerstr. 14, 72070, Tübingen, Germany; Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, Germany.
Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada; BC Children's Hospital Research Institute, 938 W 28th Ave, Vancouver, British Columbia, V5Z 4H4, Canada.
J Psychiatr Res. 2020 Jan;120:154-162. doi: 10.1016/j.jpsychires.2019.10.019. Epub 2019 Oct 26.
Early life stress (ELS) is associated with an increased risk of depression and this association may be mediated by epigenetic mechanisms. A previous epigenome-wide DNA methylation (DNAm) study investigating human newborns and two animal models of ELS suggested that the epigenetic regulator MORC1 is differentially methylated following ELS. The ELS-induced DNAm alterations were long-lasting in the animal models. However, whether this finding is also transferable to humans experiencing ELS in childhood was not investigated. Further, MORC1 may provide a link between ELS and adult depression, as MORC1 DNAm and genetic variants were found to be associated with depressive symptoms in humans. In the present study, we investigated the validity of MORC1 DNAm as a biomarker of ELS in humans and its role in linking ELS to depression later in life by studying childhood maltreatment. We analyzed whole blood MORC1 DNAm in an adult cohort (N = 151) that was characterized for both the presence of depressive symptoms and childhood maltreatment. Further, we investigated the association between MORC1 DNAm, depressive symptoms and childhood maltreatment in two additional cohorts (N = 299, N = 310). Overall, our data do not indicate an association of MORC1 DNAm with childhood maltreatment. An association of MORC1 DNAm with depressive symptoms was present in all cohorts, but was inconsistent in the specific CpG sites associated and the direction of effect (Tuebingen cohort: standardized β = 0.16, unstandardized β = 0.01, 95% CI [-0.0004, -0.0179], p = 0.061, PReDICT cohort: standardized β = -0.12, unstandardized β = -0.01, 95% CI [-0.0258, -0.0003], p = 0.045), Grady cohort: standardized β = 0.16, unstandardized β = 0.008, 95% CI [0.0019, 0.0143], p = 0.01). Our study thus suggests that peripheral MORC1 DNAm cannot serve as biomarker of childhood maltreatment in adults, but does provide further indication for the association of MORC1 DNAm with depressive symptoms.
早期生活压力 (ELS) 与抑郁风险增加有关，这种关联可能是通过表观遗传机制介导的。一项先前的全基因组 DNA 甲基化 (DNAm) 研究调查了人类新生儿和两种 ELS 动物模型，表明 ELS 后表观遗传调节剂 MORC1 的甲基化程度不同。ELS 诱导的 DNAm 改变在动物模型中是持久的。然而，这一发现是否也适用于儿童时期经历 ELS 的人类尚未得到调查。此外，MORC1 可能在 ELS 与成人抑郁症之间提供了联系，因为在人类中发现 MORC1 DNAm 和遗传变异与抑郁症状有关。在本研究中，我们通过研究儿童期虐待，研究了 MORC1 DNAm 作为人类 ELS 生物标志物的有效性及其在将 ELS 与以后生活中的抑郁联系起来的作用。我们分析了一个成年队列（N=151）的全血 MORC1 DNAm，该队列的特征是存在抑郁症状和儿童期虐待。此外，我们在另外两个队列（N=299，N=310）中研究了 MORC1 DNAm、抑郁症状和儿童期虐待之间的关联。总体而言，我们的数据并未表明 MORC1 DNAm 与儿童期虐待有关。MORC1 DNAm 与抑郁症状的关联在所有队列中均存在，但在相关 CpG 位点和效应方向上不一致（图宾根队列：标准化β=0.16，未标准化β=0.01，95%CI[-0.0004，-0.0179]，p=0.061，PReDICT 队列：标准化β=-0.12，未标准化β=-0.01，95%CI[-0.0258，-0.0003]，p=0.045），Grady 队列：标准化β=0.16，未标准化β=0.008，95%CI[0.0019，0.0143]，p=0.01）。因此，我们的研究表明，外周 MORC1 DNAm 不能作为成人儿童期虐待的生物标志物，但进一步表明 MORC1 DNAm 与抑郁症状有关。
