Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Neurosci Biobehav Rev. 2011 Jun;35(7):1544-51. doi: 10.1016/j.neubiorev.2010.12.016. Epub 2011 Jan 18.
The impact that stressful encounters have upon long-lasting behavioural phenotypes is varied. Whereas a significant proportion of the population will develop "stress-related" conditions such as post-traumatic stress disorder or depression in later life, the majority are considered "resilient" and are able to cope with stress and avoid such psychopathologies. The reason for this heterogeneity is undoubtedly multi-factorial, involving a complex interplay between genetic and environmental factors. Both genes and environment are of critical importance when it comes to developmental processes, and it appears that subtle differences in either of these may be responsible for altering developmental trajectories that confer vulnerability or resilience. At the molecular level, developmental processes are regulated by epigenetic mechanisms, with recent clinical and pre-clinical data obtained by ourselves and others suggesting that epigenetic differences in various regions of the brain are associated with a range of psychiatric disorders, including many that are stress-related. Here we provide an overview of how these epigenetic differences, and hence susceptibility to psychiatric disorders, might arise through exposure to stress-related factors during critical periods of development.
压力事件对长期行为表型的影响是多种多样的。尽管相当一部分人群在以后的生活中会发展出“与压力相关”的疾病，如创伤后应激障碍或抑郁症，但大多数人被认为是“有韧性的”，能够应对压力并避免出现此类精神病理。造成这种异质性的原因无疑是多因素的，涉及遗传和环境因素之间的复杂相互作用。在发育过程中，基因和环境都至关重要，而这些因素中的细微差异可能导致改变易感性或韧性的发育轨迹。在分子水平上，发育过程受表观遗传机制的调控，我们和其他人最近获得的临床和临床前数据表明，大脑不同区域的表观遗传差异与一系列精神疾病有关，包括许多与压力相关的疾病。在这里，我们概述了在发育的关键时期暴露于与压力相关的因素后，这些表观遗传差异以及对精神疾病的易感性是如何产生的。
