University of Wisconsin-Madison.
Max Planck Institute of Psychiatry.
Dev Psychopathol. 2017 Dec;29(5):1895-1903. doi: 10.1017/S095457941700147X.
Individuals who have experienced high levels of childhood stress are at increased risk for a wide range of behavioral problems that persist into adulthood, yet the neurobiological and molecular mechanisms underlying these associations remain poorly understood. Many of the difficulties observed in stress-exposed children involve problems with learning and inhibitory control. This experiment was designed to test individuals' ability to learn to inhibit responding during a laboratory task. To do so, we measured stress exposure among a community sample of school-aged children, and then followed these children for a decade. Those from the highest and lowest quintiles of childhood stress exposure were invited to return to our laboratory as young adults. At that time, we reassessed their life stress exposure, acquired functional magnetic resonance imaging data during an inhibitory control task, and assayed these individuals' levels of methylation in the FK506 binding protein 5 (FKBP5) gene. We found that individuals who experienced high levels of stress in childhood showed less differentiation in the dorsolateral prefrontal cortex between error and correct trials during inhibition. This effect was associated only with childhood stress exposure and not by current levels of stress in adulthood. In addition, FKBP5 methylation mediated the association between early life stress and inhibition-related prefrontal activity. These findings are discussed in terms of using multiple levels of analyses to understand the ways in which adversity in early development may affect adult behavioral adaptation.
经历过高水平童年压力的个体，发生广泛行为问题的风险增加，这些行为问题会持续到成年期，但其潜在的神经生物学和分子机制仍知之甚少。许多在压力暴露儿童中观察到的困难都涉及学习和抑制控制问题。本实验旨在测试个体在实验室任务中学习抑制反应的能力。为此，我们测量了学龄儿童社区样本中的压力暴露情况，然后对这些儿童进行了长达十年的随访。那些童年压力暴露最高和最低五分位数的个体被邀请作为年轻成年人回到我们的实验室。那时，我们重新评估了他们的生活压力暴露情况，在抑制控制任务期间获取了功能磁共振成像数据，并检测了这些个体的 FK506 结合蛋白 5（FKBP5）基因的甲基化水平。我们发现，在童年经历高水平压力的个体在抑制期间，背外侧前额叶皮层在错误和正确试验之间的分化较小。这种效应仅与童年期的压力暴露有关，而与成年期的当前压力无关。此外，FKBP5 甲基化介导了早期生活压力与抑制相关前额叶活动之间的关联。这些发现是从使用多个分析水平来理解逆境在早期发育中可能影响成年行为适应的方式的角度进行讨论的。
