Department of Psychology, University of Montreal, Montreal, Quebec, Canada.
Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
PLoS One. 2023 Jan 12;18(1):e0280203. doi: 10.1371/journal.pone.0280203. eCollection 2023.
Prospective studies suggest that child maltreatment substantially increases the risk for depression in adulthood. However, the mechanisms underlying this association require further elucidation. In recent years, DNA methylation has emerged as a potential mechanism by which maltreatment experiences (a) could partly explain the emergence or aggravation of depressive symptoms (i.e., mediation) and/or (b) could increase (or decrease) the risk for depressive symptoms (i.e., moderation). The present study tested whether the methylation levels of nine candidate genes mediated and/or moderated the association between maltreatment experiences in childhood and depressive symptoms in emerging adulthood. The sample comprised 156 men aged between 18 and 35 years. Maltreatment experiences and depressive symptoms were assessed retrospectively using self-reported questionnaires. Methylation levels of nine candidate genes (COMT, FKBP5, IL6, IL10, MAOA, NR3C1, OXTR, SLC6A3 and SLC6A4), previously reported to be sensitive to early-life stress, were quantified from saliva samples. Maltreatment experiences in childhood were significantly associated with depressive symptoms in emerging adulthood. Both maltreatment experiences and depressive symptoms were associated with the methylation levels of two genomic sites, which cumulatively, but not individually, explained 16% of the association between maltreatment experiences in childhood and depressive symptoms in emerging adulthood. Moreover, maltreatment experiences in childhood interacted with the methylation levels of fourteen genomic sites, which cumulatively, but not individually, modulated the level of depressive symptoms in young male adults who were maltreated as children. However, none of these effects survived multiple testing correction. These findings bring attention to the cumulative effects of DNA methylation measured in several candidate genes on the risk of reporting depressive symptoms following maltreatment experiences in childhood. Nonetheless, future studies need to clarify the robustness of these putative cumulative effects in larger samples and longitudinal cohorts.
前瞻性研究表明，儿童虐待会大大增加成年后患抑郁症的风险。然而，这种关联的机制仍需要进一步阐明。近年来，DNA 甲基化已成为一种潜在的机制，通过这种机制，虐待经历（a）可以部分解释抑郁症状的出现或加重（即中介作用），和/或（b）可以增加（或降低）抑郁症状的风险（即调节作用）。本研究测试了九个候选基因的甲基化水平是否介导和/或调节了儿童期虐待经历与成年早期抑郁症状之间的关联。样本包括 156 名年龄在 18 至 35 岁之间的男性。使用自我报告的问卷回顾性评估了虐待经历和抑郁症状。从唾液样本中定量测定了九个候选基因（COMT、FKBP5、IL6、IL10、MAOA、NR3C1、OXTR、SLC6A3 和 SLC6A4）的甲基化水平，这些基因先前被报道对早期生活压力敏感。儿童期的虐待经历与成年早期的抑郁症状显著相关。虐待经历和抑郁症状都与两个基因组位点的甲基化水平相关，这两个位点的总和，但不是单独的，解释了儿童期虐待经历与成年早期抑郁症状之间 16%的关联。此外，儿童期的虐待经历与 14 个基因组位点的甲基化水平相互作用，这些位点的总和，但不是单独的，调节了那些在儿童时期遭受虐待的年轻男性成年人的抑郁症状水平。然而，这些影响在多重测试校正后都没有幸存下来。这些发现引起了人们对在几个候选基因中测量的 DNA 甲基化的累积效应在儿童期虐待经历后报告抑郁症状风险的关注。然而，未来的研究需要在更大的样本和纵向队列中阐明这些潜在的累积效应的稳健性。
