Development of a biopsychosocial translational research programme in post-traumatic stress disorder.

创伤后应激障碍(PTSD)是一种复杂的精神障碍，会给患有创伤后应激障碍的人带来社会和职业上的困难。这种障碍是由一生中暴露在创伤性事件中引发的，其特征是侵入性记忆和回避行为等症状。多项研究已经确定了多种遗传因素，这些因素会增加一个人在经历创伤事件后患上创伤后应激障碍的风险。然而，这些研究已经确定了许多基因，而关于这些遗传因素在创伤后应激障碍中的确切作用的研究很少。此外，我们对这种疾病的确切神经生物学基础以及这些基础如何与社会和心理结构相互作用知之甚少，因此需要更多的研究来了解创伤后应激障碍患者大脑中的哪些过程发生变化，以便找到有效的治疗方法。最近，一种与突触传递(神经元之间的通讯)有关的蛋白质--神经连接素1(NLGN1)--被认为与PTSD的发病风险有关。这种蛋白以前曾被认为与其他与创伤后应激障碍相关的精神障碍有关，如焦虑和严重抑郁障碍，以及精神分裂症。NLGN1蛋白在创伤后应激障碍的发生发展中的作用尚不清楚，但最近的一些研究表明，它在创伤后应激障碍和应激行为的调节中发挥着重要作用。这项建议的目的是开发一个转化性研究计划，整合实验室和临床研究，以更好地了解创伤后应激障碍的脆弱性和复原力。我们建议为哥伦比亚塞萨尔部门市政当局暴露在武装冲突中的人群制定一项心理健康计划。在这里，我们首先将流行病学、临床和生物学方法结合起来，对暴露在哥伦比亚武装冲突中的人的创伤后应激障碍的风险因素、症状和结果进行全面评估。同时，我们将使用斑马鱼动物模型来操纵NLGN1基因，并研究这种变化如何影响斑马鱼对压力、焦虑和大脑中基因表达模式的反应。最后，我们将结合这项研究的两个组成部分，通过评估NLGN1基因及其途径上的其他基因在我们在哥伦比亚塞萨尔的研究队列中研究的PTSD患者中的差异程度。我们的工作将极大地有助于理解创伤后应激障碍的分子基础，以及目前缺乏关于拉美裔人群创伤后应激障碍风险和复原力因素的数据，同时为长期受到暴力影响的人群提供心理健康计划的机会。这项研究的结果可以转让并应用于改善公共卫生政策，以改善哥伦比亚武装冲突受害者的心理健康和生活质量。

Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric disorder that generates social and profesional difficulties for those who suffer from it. This disorder is triggered by exposure to traumatic events throughout life and characterized by symptoms such as intrusive memories and avoidance behaviors. Multiple studies have identified multiple genetic factors that increase a person's risk of developing PTSD after exposure to a traumatic event. However, these studies have identified many genes and research on the precise role of each of these genetic elements in PTSD is scarce. Moreover, we know very little about the precise neurobiological bases of this disorder and how these interact with social and psychological constructs, and thus more research is needed to understand which processes in the brain become altered in PTSD in order to find an efficient treatment. Recently, a protein involved in synaptic transmission (communication between neurons), neuroligin 1 (nlgn1), has been linked to the risk of developing PTSD. This protein has been previously linked to other psychiatric disorders associated with PTSD, such as anxiety and major depressive disorder, and schizophrenia. The role of the nlgn1 protein in the development of PTSD is unknown, but a number of recent studies suggest it plays an important role in PTSD and the modulation of stress behavior in general. The aim of this proposal is to develop a translational research program, integrating laboratory and clinical research to better understand vulnerability and resilience for PTSD. We propose to develop a mental health program for populations exposed to the armed conflict in municipalities of the department of Cesar, Colombia. Here, we will initially combine epidemiological, clinical and biological approaches to perform a complete evaluation of risk factors, symptoms and outcomes of PTSD in people exposed to the Colombian armed conflict. In parallel we will use a zebrafish animal model to manipulate the nlgn1 gene and study how this alteration affects zebrafish response to stress, anxiety and patterns of gene expression in the brain. Finally, we will combine both components of this study by evaluating how much the nlgn1 gene, and other genes along its pathway, vary across the studied PTSD patients in our study cohort in Cesar, Colombia. Our work will greatly contribute to understanding the molecular underpinnings of PTSD, as well as currently lacking data on PTSD risk and resilience factors among Latino populations, while providing access to a mental health program in a population long affected by violence. Findings of this study could be transferred and applied to the improvement of public health policies to improve the psychological wellbeing and quality of life of those exposed to armed conflict in Colombia.