Investigating the role of neuropsychological processes in stress induced negative affective states and assocaited behaviour

压力相关障碍是西方社会造成社会和经济损失的主要问题。压力与精神疾病的发展密切相关，超过20%的人直接受到焦虑或抑郁的影响。压力还与其他疾病有关，包括身心障碍（腰痛、胃肠疾病，如肠易激综合症）、成瘾和肥胖。尽管治疗压力相关疾病（如抑郁症）的药物早在20世纪50年代就被发现，但科学家们发现，很难解释这些药物是如何在大脑中发挥作用来治疗这种疾病的症状的，以及为什么患者需要几周时间才能开始感觉好转。研究大脑以及它如何控制我们的行为，包括我们的情绪行为，是复杂的，精神疾病是最大的挑战之一。虽然对患者的研究使用问卷调查、访谈、脑成像技术和心理学，但对动物的实验对于解开大脑的特定部分和涉及的脑化学非常重要。动物试验对于开发新的治疗方法也非常重要，对于确定一种药物是否可能对患者有效并因此适合进行临床试验至关重要。在这个项目中，我们的目标是将压力相关生物学的两个方面结合起来，并测试一个新的假设。我们感兴趣的两个领域是：1。大脑结构中与压力相关的变化与压力相关的行为改变，例如动机降低、快乐体验减少、冷漠和社交退缩。直到最近，对动物的研究主要集中在与压力相关的大脑结构变化上，而现有的行为测试几乎没有揭示这些变化与人类状况的关系。虽然对压力相关条件的基础生物学研究更多地集中在分子和细胞方面，但临床研究最近开始关注心理过程，试图为患者观察到的症状提供更好的解释。我们现在开发了一种新的方法来研究动物的情绪行为，这种方法利用了类似的心理过程。我们现在处于独特的位置，可以开展研究，直接评估压力如何影响大脑的行为和结构变化。我们预测，我们的研究将揭示认知情感过程是影响行为的关键机制，而不是作为结构适应的结果产生的。我们还预测，与压力有关的疾病的症状，如动机降低、快乐体验减少、冷漠和社交退缩，实际上会导致大脑的结构变化。我们的研究有可能揭示压力诱发的消极情绪行为和大脑结构变化所涉及的神经心理过程之间的重要因果关系。如果我们成功地实现了这一点，这项工作的结果将对我们未来如何针对人类的压力相关疾病产生重大影响。它还将为不同类型的压力的影响、持续时间以及它们对未来压力和情绪障碍的脆弱性的长期影响提供新的见解。因为我们的工作是在动物身上进行的，所以它也会影响我们在动物福利的背景下如何考虑压力。

Stress-related disorders are a major issue in western society contributing to both social and economic loss. Stress is strongly associated with development of psychiatric disorders with more than 20% of the population directly affected by either anxiety or depression. Stress is also associated with other conditions including psychosomatic disturbances (lower back pain, gastrointestinal diseases such as irritable bowl syndrome), addiction and obesity. Although drugs to treat stress-related conditions, such as depression, were discovered in the 1950s, scientists have found it difficult to explain how they act in the brain to treat the symptoms of the disease and why it takes several weeks before the patient starts to feel better. Studying the brain and how it controls our behaviour, including our emotional behaviour, is complicated and psychiatric disorders represent one of the biggest challenges. Whilst studies in patients use questionnaires, interviews, brain imaging techniques and psychology, experiments in animals are important to unlock the specific parts of the brain and brain chemistry involved. Animal tests are also very important for the development of new treatments and are essential to establishing whether a drug is likely to be effective in a patient and therefore suitable for clinical trials. In this project, we aim to bring together two aspects of stress-related biology and test a novel hypothesis. The two areas we are interested in are:1. Stress-related changes in brain structure2. Stress-related changes in behaviour e.g. reduced motivation, reduced experience of pleasure, apathy and social withdrawal.Until very recently, studies in animals have largely concentrated on stress-related changes in brain structure with the behavioural tests available revealing little about how these relate to the human conditions. Whilst research into the basic biology of stress-related conditions has focused on the more molecular and cellular aspects, clinical research has recently looked toward psychological processes to try to provide a better explanation for the symptoms observed in patients. We have now developed a new method to study emotional behaviour in animals which taps into similar psychological processes. We are now in the unique position to carryout studies to directly assess how stress impacts on both behavioural and structural changes in the brain. We predict that our studies will reveal that cognitive affective processes are the key mechanisms influencing behaviour rather than arising as a consequence of structural adaptation. We also predict that the symptoms of stress-related disorders, such as reduced motivation, reduced experience of pleasure, apathy and social withdrawal, in fact cause the structural changes in the brain.Our research has the potential to reveal an important causal relationship between neuropsychological processes implicated in stress-induced negative emotional behaviour and structural changes in the brain. If we are successful in achieving this, the results of this work will have a major impact on how we target stress-related conditions in man in the future. It will also provide new insights into the impact of different types of stress, their duration and their long term impact on vulnerability to future stress and emotional disorders. Because our work is in animals, it will also impact on how we consider stress in the context of animal welfare.