The neurobiology of cognitive affective biases in depression and their role in antidepressant therapy

抑郁症认知情感偏差的神经生物学及其在抗抑郁治疗中的作用

• 批准号: MR/L011212/1
• 负责人: Emma Robinson
• 金额: $ 61.38万
• 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=MR%2FL011212%2F1
• 关键词: neurobiology; cognitive; affective; biases; depression

Depression is the most significant psychiatric illness affecting people in the UK. Costs to society were estimated at £8.6 billion in 2009 and the World Health Organisation predicts that depression will soon be the leading cause of years lived with a disability. Although drugs to treat 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. Because animals lack the ability to express emotional impairments in terms of the methods used to study these symptoms in patients, progress towards understanding the neurobiology of depressed mood and its treatment has been limited. Recent research has demonstrated the feasibility of measuring emotion-related behaviour in rats and this project will build on this using an assay developed in our laboratory, the affective bias test. In this project we will use our task to investigate a novel hypothesis about the cause and treatment of depression. We will also investigate whether these changes in cognition are correlated with changes in motivation to engage in social and environmental interactions. Individuals with depression report persistent negative mood which is associated with a tendency to remember things in a negative way. Thus, a patient with depression will have the same experiences as a non-depressed patient but when asked to recall those experiences, they will remember more negative things than the non-depressed individual. This is thought to arise from negative cognitive processing which in turn affects motivation to re-engage in those activities and results in the progressive social and environmental withdrawal associated with depression. It is also now thought that antidepressant drugs act to modify psychological processes so these negative processing biases are reversed and the patient gradually learns new positively biased memories which increase motivation to re-engage in social and environmental interactions. This hypothesis may also help to explain why either drug treatment or cognitive behavioural therapies are effective in some patients with depression.Using our animal experiments, we are able to test these ideas without the difficulties of controlling other factors encountered when studying patients with depression. We can also map the time course of change in emotional processing and behaviour and relate these to a possible mechanism of disease development and treatment reversal. We have also planned a series of experiments which will look at which part of the brain is most important in mediating these cognitive effects and whether targeting this region selectively can induce a rapid reversal of depressed symptoms. Together these experiments will provide new information about the role of cognitive mechanisms in the cause and treatment of depression.

抑郁症是影响英国人民的最重要的精神疾病，2009 年估计造成的社会损失为 86 亿英镑，世界卫生组织预测，尽管治疗抑郁症的药物众多，但抑郁症很快将成为导致残疾的主要原因。发现于 20 世纪 50 年代，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。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了问卷、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非常重要。对于新疗法的开发也非常重要，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，因为动物缺乏根据研究方法表达情绪障碍的能力。患者的这些症状，在理解抑郁情绪的神经生物学方面取得了进展，最近的研究证明了测量大鼠情绪相关行为的可行性，该项目将在此基础上使用我们实验室开发的情感偏差测试来研究分析。我们还将研究这些认知变化是否与参与社交和环境互动的动机变化相关，抑郁症患者报告持续的负面情绪，这与记住事物的倾向有关。因此，抑郁症患者也会有同样的情况。作为一个非抑郁症患者，他们会经历一些经历，但当被要求回忆这些经历时，他们会比非抑郁症患者记住更多消极的事情，这被认为是由消极的认知过程引起的，这反过来会影响重新参与这些活动的动机。导致与抑郁症相关的渐进性社交和环境退缩，现在人们还认为，抗抑郁药物可以改变心理过程，从而逆转这些消极处理偏差，患者逐渐学习新的积极偏见记忆，从而增加重新参与社交活动的动力。这个假设也可能有帮助。解释为什么药物治疗或认知行为疗法对某些抑郁症患者有效。通过我们的动物实验，我们能够测试这些想法，而无需控制研究抑郁症患者时遇到的其他因素。我们还可以绘制时间图。我们还计划了一系列实验，研究大脑的哪一部分在调节这些认知效应中最重要，以及是否有针对性。该区域选择性地可以引起快速逆转这些实验将共同提供有关认知机制在抑郁症的病因和治疗中的作用的新信息。

项目成果

Development of a novel rodent rapid serial visual presentation task reveals dissociable effects of stimulant versus nonstimulant treatments on attentional processes

• DOI: 10.3758/s13415-023-01152-x
• 发表时间: 2024-01-22
• 期刊: COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
• 影响因子: 2.9
• 作者: Benn，Abigail;Robinson，Emma S. J.
• 通讯作者: Robinson，Emma S. J.

sj-docx-1-bna-10.1177_23982128211015110 - Supplemental material for Evidence for deficits in behavioural and physiological responses in aged mice relevant to the psychiatric symptom of apathy

sj-docx-1-bna-10.1177_23982128211015110 - 与冷漠精神症状相关的老年小鼠行为和生理反应缺陷证据的补充材料

• DOI: 10.25384/sage.14684223
• 发表时间: 2021
• 作者: Jackson M

Evidence for deficits in behavioural and physiological responses in aged mice relevant to the psychiatric symptom of apathy.

• DOI: 10.1177/23982128211015110
• 发表时间: 2021-01
• 期刊: Brain and neuroscience advances
• 作者: Jackson MG;Lightman SL;Gilmour G;Marston H;Robinson ESJ
• 通讯作者: Robinson ESJ

Investigating neuropsychological and reward-related deficits in a chronic corticosterone-induced model of depression.

• DOI: 10.1016/j.psyneuen.2022.105953
• 发表时间: 2023-01
• 期刊: PSYCHONEUROENDOCRINOLOGY
• 影响因子: 3.7
• 作者: Hales, Claire A.;Stuart, Sarah A.;Griffiths, Jennifer;Bartlett, Julia;Arban, Roberto;Hengerer, Bastian;Robinson, Emma S. J.
• 通讯作者: Robinson, Emma S. J.

Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats.

• DOI: 10.1016/j.euroneuro.2017.09.008
• 发表时间: 2017-12
• 期刊: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
• 作者: Hales CA;Houghton CJ;Robinson ESJ
• 通讯作者: Robinson ESJ