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

点击翻译按钮获取中文摘要

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.