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

创伤后应激障碍（Post-Traumatic Stress Disorder，PTSD）是一种复杂的精神疾病，会给患者带来社交和职业上的困难。这种疾病是由一生中暴露于创伤性事件引发的，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暴露于创伤事件后患上PTSD的风险。然而，这些研究已经确定了许多基因，而关于这些基因中的每一个在PTSD中的确切作用的研究却很少。此外，我们对这种疾病的精确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中大脑中的哪些过程发生改变，以便找到有效的治疗方法。最近，一种参与突触传递（神经元之间的通信）的蛋白质，神经连接素1（nlgn 1），已与发生PTSD的风险有关。这种蛋白质以前与其他与PTSD相关的精神疾病有关，如焦虑和重度抑郁症以及精神分裂症。nlgn 1蛋白在PTSD发展中的作用尚不清楚，但最近的一些研究表明，它在PTSD和一般应激行为的调节中起着重要作用。该提案的目的是开发一个转化研究计划，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恢复力。我们建议为哥伦比亚塞萨尔省各城市受武装冲突影响的人口制定一项心理健康方案。在这里，我们将首先结合联合收割机流行病学，临床和生物学的方法来执行一个完整的评估风险因素，症状和结果的创伤后应激障碍的人暴露于哥伦比亚武装冲突。与此同时，我们将使用斑马鱼动物模型来操纵nlgn 1基因，并研究这种改变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，我们将联合收割机这两个组成部分的研究，通过评估有多少nlgn 1基因，和其他基因沿着其途径，在我们的研究队列中研究的创伤后应激障碍患者在哥伦比亚的塞萨尔。我们的工作将极大地有助于了解PTSD的分子基础，以及目前缺乏关于拉丁裔人群中PTSD风险和弹性因素的数据，同时为长期受暴力影响的人群提供心理健康计划。这项研究的结果可以转移和应用于改善公共卫生政策，以改善那些暴露在哥伦比亚武装冲突中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.