Cecil Charlotte A M, Smith Rebecca G, Walton Esther, Mill Jonathan, McCrory Eamon J, Viding Essi
Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK; University of Exeter Medical School, University of Exeter, Exeter, EX1 2LU, UK.
J Psychiatr Res. 2016 Dec;83:184-194. doi: 10.1016/j.jpsychires.2016.09.010. Epub 2016 Sep 13.
Childhood maltreatment is a key risk factor for poor mental and physical health. Recently, variation in epigenetic processes, such as DNA methylation, has emerged as a potential pathway mediating this association; yet, the extent to which different forms of maltreatment may be characterized by unique vs shared epigenetic signatures is currently unknown. In this study, we quantified DNA methylation across the genome in buccal epithelial cell samples from a high-risk sample of inner-city youth (n = 124; age = 16-24; 53% female), 68% of whom reported experiencing at least one form of maltreatment while growing up. Our analyses aimed to identify methylomic variation associated with exposure to five major types of childhood maltreatment. We found that: (i) maltreatment types differ in the extent to which they associate with methylomic variation, with physical exposures showing the strongest associations; (ii) many of the identified loci are annotated to genes previously implicated in stress-related outcomes, including psychiatric and physical disorders (e.g. GABBR1, GRIN2D, CACNA2D4, PSEN2); and (iii) based on gene ontology analyses, maltreatment types not only show unique methylation patterns enriched for specific biological processes (e.g. physical abuse and cardiovascular function), but also share a 'common' epigenetic signature enriched for biological processes related to neural development and organismal growth. A stringent set of sensitivity analyses were also run to identify high-confidence associations. Together, findings lend novel insights into epigenetic signatures of childhood abuse and neglect, point to novel potential biomarkers for future investigation and support a molecular link between maltreatment and poor health outcomes. Nevertheless, it will be important in future to replicate findings, as the use of cross-sectional data and high rates of polyvictimization in our study make it difficult to fully disentangle the shared vs unique epigenetic signatures of maltreatment types. Furthermore, studies will be needed to test the role of potential moderators in the identified associations, including age of onset and chronicity of maltreatment exposure.
童年期受虐是心理健康和身体健康不佳的关键风险因素。最近，诸如DNA甲基化等表观遗传过程的变化已成为介导这种关联的潜在途径；然而，目前尚不清楚不同形式的虐待在多大程度上可能具有独特的与共同的表观遗传特征。在本研究中，我们对来自市中心高危青年样本（n = 124；年龄 = 16 - 24岁；53%为女性）的颊上皮细胞样本中的全基因组DNA甲基化进行了定量，其中68%的人报告在成长过程中经历过至少一种形式的虐待。我们的分析旨在识别与暴露于五种主要类型童年期虐待相关的甲基化组变异。我们发现：（i）虐待类型在与甲基化组变异的关联程度上存在差异，身体虐待的关联最强；（ii）许多已识别的基因座被注释到先前与应激相关结果有关的基因，包括精神和身体疾病（如GABBR1、GRIN2D、CACNA2D4、PSEN2）；（iii）基于基因本体分析，虐待类型不仅显示出富含特定生物学过程（如身体虐待和心血管功能）的独特甲基化模式，而且还共享一种“共同的”表观遗传特征，该特征富含与神经发育和机体生长相关的生物学过程。我们还进行了一系列严格的敏感性分析以识别高可信度的关联。总之，这些发现为童年期虐待和忽视的表观遗传特征提供了新的见解，指出了未来研究的新潜在生物标志物，并支持了虐待与不良健康结果之间的分子联系。然而，未来重复这些发现将很重要，因为我们研究中使用的横断面数据和高多重受害率使得难以完全厘清虐待类型的共同与独特表观遗传特征。此外，还需要开展研究来测试潜在调节因素在已识别关联中的作用，包括虐待开始的年龄和虐待暴露的慢性程度。
