Anxiety, Fear and Human Defensive Reactions: Behavioural Differentiation of Generalised Anxiety Disorder and Panic Disorder

在这项研究中，我们试图通过使用一种翻译实验范式-操纵杆操作跑道任务(JORT)，在行为水平上分离恐惧和焦虑的原因机制。JORT是人类对啮齿动物任务的翻译，它允许测量简单回避(恐惧)和接近-撤退振荡(焦虑)的可分离行为成分。我们之前已经开发了JORT，并两次从药理学上验证了它，这表明这项任务可以测量人类防御行为的这两个组成部分。在这里，我们想应用这项任务来研究两种临床情况，广泛性焦虑症(GAD)和惊恐障碍(PD)。从防御行为的角度来看，这些障碍被假设为可分离的，GAD涉及目标冲突，反映在更多的接近-撤退行为上，PD涉及更多的恐惧，导致逃跑。在我们之前使用JORT的基础上，我们推测它是从一个已建立的动物模型发展而来的，这导致了一种新的、真正的翻译范式，这种范式可能对人类焦虑和恐惧倾向的行为测量有用。该任务具有表面效度，我们已经积累了结构效度的证据。总而言之，这些证据表明，JORT可能会利用GAD和PD背后的维度的重要差异。然而，两个重要的问题仍然存在。首先，我们需要确定焦虑症患者总体上是否表现出比健康对照组更强烈的防御行为。其次，我们需要确定JORT的两个组成部分是否如假设的那样映射到GAD和PD的临床诊断上。因此，在这项研究中，我们的目标是将JORT应用于GAD患者(N=30)、PD患者(N=30)和健康对照组(N=30)的样本。总体而言，这项拟议的研究旨在通过在神经行为水平上剖析这些障碍，从而为我们对GAD和PD的理解做出重大贡献，该研究使用了一个理论框架，该框架认为焦虑和恐惧作为哺乳动物固有防御能力的一部分具有功能意义。

In this study we attempt to dissociate, at a behavioural level, the causal mechanisms of fear and anxiety through the use of a translational experimental paradigm, the Joystick Operated Runway Task (JORT). The JORT is the human translation of a rodent task which allows the measurement of the separable behavioural components of simple avoidance (fear) and approach-withdrawal oscillations (anxiety). We have previously developed the JORT and twice validated it pharmacologically, suggesting the task allows the measurement of these two components of human defensive behaviour. Here we would like to apply the task in order to study two clinical conditions, generalised anxiety disorder (GAD) and panic disorder (PD). These disorders are hypothesised to be dissociable from the perspective of defensive behaviour, with GAD involving goal conflict, reflected in increased approach-withdrawal behaviour, and PD involving increased fear, resulting in flight. On the basis of our previous work using the JORT, we surmise that its development from an established animal model has led to a novel and truly translational paradigm that may be useful in the behavioural measurement of human anxiety- and fear-proneness. The task has face validity and we have accumulated evidence of construct validity. Together this evidence suggests that the JORT may tap important variance of the dimensions underlying GAD and PD. However, two important questions remain. First, we need to establish whether anxiety disorder patients, in general, show more intense defensive behaviour than healthy controls. Second we need to determine if the two component processes of the JORT map onto the clinical diagnoses of GAD and PD, as hypothesised. Therefore, in this study we aim to apply the JORT to samples of patients with GAD (N=30), patients with PD (N=30), and healthy controls (N=30). Overall, the proposed research intends to make a significant contribution to our understanding of GAD and PD by dissecting these disorders at the neurobehavioural level using a theoretical framework that maintains that anxiety and fear have functional significance as part of the innate mammalian defensive repertoire.