Mill J, Petronis A
The Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Mol Psychiatry. 2007 Sep;12(9):799-814. doi: 10.1038/sj.mp.4001992. Epub 2007 Apr 10.
Major depressive disorder (MDD) is a common and highly heterogeneous psychiatric disorder encompassing a spectrum of symptoms involving deficits to a range of cognitive, psychomotor and emotional processes. As is the norm for aetiological studies into the majority of psychiatric phenotypes, particular focus has fallen on the interplay between genetic and environmental factors. There are, however, several epidemiological, clinical and molecular peculiarities associated with MDD that are hard to explain using traditional gene- and environment-based approaches. Our goal in this study is to demonstrate the benefits of looking beyond conventional 'DNA+environment' and 'DNA x environment' aetiological paradigms. Epigenetic factors - inherited and acquired modifications of DNA and histones that regulate various genomic functions occurring without a change in nuclear DNA sequence - offer new insights about many of the non-Mendelian features of major depression, and provide a direct mechanistic route via which the environment can interact with the genome. The study of epigenetics, especially in complex diseases, is a relatively new field of research, and optimal laboratory techniques and analysis methods are still being developed. Incorporating epigenetic research into aetiological studies of MDD thus presents a number of methodological and interpretive challenges that need to be addressed. Despite these difficulties, the study of DNA methylation and histone modifications has the potential to transform our understanding about the molecular aetiology of complex diseases.
重度抑郁症（MDD）是一种常见且高度异质性的精神障碍，涵盖一系列症状，涉及多种认知、心理运动和情感过程的缺陷。正如大多数精神疾病表型病因学研究的常态一样，特别关注的是遗传因素与环境因素之间的相互作用。然而，与MDD相关的有几个流行病学、临床和分子方面的特性，用传统的基于基因和环境的方法很难解释。我们这项研究的目标是证明超越传统的“DNA+环境”和“DNA×环境”病因学范式的益处。表观遗传因素——DNA和组蛋白的遗传和获得性修饰，可调节各种基因组功能，且不改变核DNA序列——为重度抑郁症的许多非孟德尔特征提供了新的见解，并提供了一条环境与基因组相互作用的直接机制途径。表观遗传学研究，尤其是在复杂疾病中的研究，是一个相对较新的研究领域，最佳的实验室技术和分析方法仍在不断发展。因此，将表观遗传学研究纳入MDD的病因学研究中提出了一些需要解决的方法学和解释性挑战。尽管存在这些困难，但DNA甲基化和组蛋白修饰的研究有可能改变我们对复杂疾病分子病因的理解。
