MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
J Psychiatr Res. 2013 Aug;47(8):1032-5. doi: 10.1016/j.jpsychires.2013.03.017. Epub 2013 Apr 22.
Both childhood maltreatment and adult stressful life events are established risk factors for the onset of depression in adulthood. However, the interaction between them can be viewed through two conflicting frameworks. Under a mismatch hypothesis stressful childhoods allow 'adaptive programming' for a stressful adulthood and so can be protective. Only when childhood and adulthood do not match is there a risk of behavioural problems. Alternatively, under the cumulative stress hypothesis we expect increased risk with each additional stressor. It has also been suggested that an individual's genetic background may determine the extent they undergo adaptive programming, and so which of these two hypotheses is relevant. In this study we test for an interaction between exposure to childhood maltreatment and adult stressful life events in a retrospective sample of 455 individuals, using major depression as the outcome. We also test whether this interaction differs by genotype at the 5-HTTLPR, a candidate for an individual's plasticity to adaptive programming. Early maltreatment and stressful life events in adulthood interacted to produce increased risk for depression over each individually (p = 0.055). This supports the cumulative stress hypothesis over the mismatch hypothesis, at least with respect to severe environmental risk factors. This effect was not altered by 5-HTTLPR allele, suggesting there was no difference by genotype in adaptive programming to these events. We suggest that the apparent additional vulnerability to stressful events of those who have experienced maltreatment has clinical relevance, highlighting the importance of providing support beyond the immediate aftermath of maltreatment into adulthood.
儿童期虐待和成年期压力性生活事件都是成年期抑郁症发病的既定风险因素。然而，它们之间的相互作用可以通过两种相互冲突的框架来看待。在不匹配假设下，压力大的童年期允许为成年期的压力做好“适应性编程”，从而起到保护作用。只有当童年期和成年期不匹配时，才会有行为问题的风险。或者，在累积性应激假说下，我们预计每个额外的应激源都会增加风险。有人还提出，个体的遗传背景可能决定了他们进行适应性编程的程度，因此这两个假设中的哪一个更为相关。在这项研究中，我们使用回顾性样本中的 455 个人，以重度抑郁症为结果，检验了儿童期虐待和成年期压力性生活事件之间的相互作用。我们还测试了这种相互作用是否因 5-HTTLPR 的基因型而有所不同，5-HTTLPR 是个体对适应性编程的可塑性的候选基因。早期的虐待和成年期的压力性生活事件相互作用，使每种情况下的抑郁风险增加（p=0.055）。这至少在严重的环境风险因素方面支持了累积性应激假说，而不是不匹配假说。这种效应不受 5-HTTLPR 等位基因的影响，这表明在对这些事件进行适应性编程方面，基因型没有差异。我们认为，那些经历过虐待的人对压力事件的明显额外脆弱性具有临床意义，这凸显了在虐待事件发生后，为成年期提供支持的重要性。
