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

研究神经心理过程在压力引起的消极情感状态和相关行为中的作用

• 批准号: BB/L009137/1
• 负责人: Emma Robinson
• 金额: $ 31.03万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL009137%2F1
• 关键词: Investigating; role; neuropsychological; processes; stress

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.

压力相关障碍是西方社会的一个主要问题，造成社会和经济损失。压力与精神疾病的发展密切相关，超过20%的人口直接受到焦虑或抑郁的影响。压力也与其他疾病有关，包括心身障碍（下背痛，胃肠道疾病，如肠易激综合征），成瘾和肥胖。尽管在20世纪50年代就发现了治疗抑郁症等与压力有关的疾病的药物，但科学家们发现很难解释它们如何在大脑中发挥作用来治疗疾病的症状，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，大脑成像技术和心理学，但动物实验对于解开大脑的特定部分和所涉及的大脑化学物质非常重要。动物试验对于开发新的治疗方法也非常重要，并且对于确定药物是否可能对患者有效并因此适合临床试验至关重要。在这个项目中，我们的目标是汇集压力相关生物学的两个方面，并测试一个新的假设。我们感兴趣的两个领域是：1。压力相关的大脑结构变化2.与压力有关的行为变化，例如动力减少、快乐体验减少、冷漠和社交退缩。直到最近，动物研究主要集中在与压力有关的大脑结构变化上，现有的行为测试很少揭示这些变化与人类状况的关系。虽然对压力相关疾病的基础生物学研究集中在更多的分子和细胞方面，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。我们现在已经开发出一种研究动物情感行为的新方法，该方法利用了类似的心理过程。我们现在处于独特的地位，可以进行研究，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，而不是结构适应的结果。我们还预测，与压力相关的疾病的症状，例如动机降低、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与压力相关的神经心理过程之间的重要因果关系压力诱导的负面情绪行为和大脑结构变化。如果我们成功地实现了这一目标，这项工作的结果将对我们未来如何针对人类与压力相关的状况产生重大影响。它还将为不同类型的压力的影响、其持续时间及其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，它也将影响我们如何在动物福利的背景下考虑压力。

项目成果

Modelling cognitive affective biases in major depressive disorder using rodents.

• DOI: 10.1111/bph.12603
• 发表时间: 2014-10
• 期刊: British journal of pharmacology
• 影响因子: 7.3
• 作者: Hales CA;Stuart SA;Anderson MH;Robinson ES
• 通讯作者: Robinson ES

Rapid-acting antidepressant drugs modulate affective bias in rats.

• DOI: 10.1126/scitranslmed.adi2403
• 发表时间: 2024-01-10
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Hinchcliffe JK;Stuart SA;Wood CM;Bartlett J;Kamenish K;Arban R;Thomas CW;Selimbeyoglu A;Hurley S;Hengerer B;Gilmour G;Robinson ESJ
• 通讯作者: Robinson ESJ

Pharmacological characterisation of the effort for reward task as a measure of motivation for reward in male mice.

• DOI: 10.1007/s00213-023-06420-9
• 发表时间: 2023-11
• 期刊: PSYCHOPHARMACOLOGY
• 影响因子: 3.4
• 作者: Marangoni, Caterina;Tam, Melissa;Robinson, Emma S. J.;Jackson, Megan G.
• 通讯作者: Jackson, Megan G.

Investigating hormone-induced changes in affective state using the affective bias test in male and female rats.

使用雄性和雌性大鼠的情感偏差测试来研究激素引起的情感状态变化。

• DOI: 10.1016/j.psyneuen.2020.104647
• 发表时间: 2020
• 期刊: Psychoneuroendocrinology
• 影响因子: 3.7
• 作者: Hinchcliffe JK

Pavlovian influences on learning differ between rats and mice in a counter-balanced Go/NoGo judgement bias task.

• DOI: 10.1016/j.bbr.2017.05.044
• 发表时间: 2017-07-28
• 期刊: Behavioural brain research
• 影响因子: 2.7
• 作者: Jones S;Paul ES;Dayan P;Robinson ESJ;Mendl M
• 通讯作者: Mendl M