Post-Traumatic Stress Disorder (PTSD) is a complex condition that develops after experiencing a severe emotional trauma, with or without physical trauma. There is no known cure and evidence-based treatments, which are effective in reducing symptoms, have low retention rates. It is therefore important, in addition to seeking new therapeutics, to identify ways to reduce the likelihood of developing PTSD. The fact that some, but not all, individuals exposed to the same traumatic event develop PTSD suggests that there is individual susceptibility. Investigating susceptibility and underlying factors will be better guided if there is a coherent framework for such investigations. In this review, we propose that susceptibility is a dynamic state that is comprised of susceptibility factors (before trauma) and sequalae factors (during or after trauma, but before PTSD diagnosis). We define key features of susceptibility and sequalae factors as: (1) they are detectable before trauma (susceptibility factors) or during/shortly after trauma (sequalae factors), (2) they can be manipulated, and (3) manipulation of these factors alters the likelihood of developing PTSD, thus affecting resilience. In this review we stress the importance of investigating susceptibility to PTSD with appropriate animal models, because prospective human studies are expensive and manipulation of susceptibility and sequalae factors for study purposes may not always be feasible. This review also provides a brief overview of a subset of animal models that study PTSD-related behaviors and related alterations in endocrine and brain systems that focus on individual differences, peri- and post-trauma. Attention is drawn to the RISP model (Revealing Individual Susceptibility to a PTSD-like Phenotype) which assesses susceptibility before trauma. Using the RISP model and expression of plasticity-associated immediate early genes, Arc and Homer1a, we have identified impaired hippocampal function as a potential susceptibility factor. We further discuss other putative susceptibility factors and approaches to mitigate them. We assert that this knowledge will guide successful strategies for interventions before, during or shortly after trauma that can decrease the probability of developing PTSD.

中文翻译：

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研究个体创伤前对动物 PTSD 样表型的易感性

创伤后应激障碍 (PTSD) 是一种复杂的疾病，在经历严重的情感创伤后发展，无论是否有身体创伤。没有已知的治愈方法和循证治疗，可有效减轻症状，保留率低。因此，除了寻求新的治疗方法外，重要的是要确定降低患 PTSD 可能性的方法。一些（但不是全部）暴露于相同创伤事件的个体发展为 PTSD 的事实表明存在个体易感性。如果此类调查有一个连贯的框架，那么对易感性和潜在因素的调查将得到更好的指导。在这篇综述中，我们提出易感性是一种动态状态，由易感因素（创伤前）和后遗症因素（创伤中或创伤后，但在 PTSD 诊断之前）。我们将易感性和后遗症因素的关键特征定义为：（1）它们在创伤前（易感性因素）或创伤期间/后不久（后遗症因素）是可检测到的，（2）它们可以被操纵，以及（3）对这些因素的操纵改变发生 PTSD 的可能性，从而影响恢复力。在这篇综述中，我们强调了用适当的动物模型研究 PTSD 易感性的重要性，因为前瞻性人体研究成本高昂，而且出于研究目的对易感性和后遗症因素进行操作可能并不总是可行的。本综述还简要概述了研究 PTSD 相关行为以及内分泌和大脑系统相关改变的动物模型子集，重点关注个体差异、创伤前后和创伤后。提请注意 RISP 模型（揭示个体对 PTSD 样表型的易感性），该模型在创伤前评估易感性。使用 RISP 模型和可塑性相关的即刻早期基因 Arc 和 Homer1a 的表达，我们已将受损的海马功能确定为潜在的易感因素。我们进一步讨论了其他假定的易感因素和减轻它们的方法。我们断言，这些知识将指导在创伤之前、之中或之后不久进行干预的成功策略，从而降低发生 PTSD 的可能性。我们已经确定海马功能受损是一个潜在的易感因素。我们进一步讨论了其他假定的易感因素和减轻它们的方法。我们断言，这些知识将指导在创伤之前、之中或之后不久进行干预的成功策略，从而降低发生 PTSD 的可能性。我们已经确定海马功能受损是一个潜在的易感因素。我们进一步讨论了其他假定的易感因素和减轻它们的方法。我们断言，这些知识将指导在创伤之前、之中或之后不久进行干预的成功策略，从而降低发生 PTSD 的可能性。