The Neurobiology of Mood Disorders

Depression and bipolar disorder are clinical disturbances of mood, which are common and serious conditions. The medical importance of mood disorders is often underestimated but the World Health Organisation has predicted that depression will be the second most important cause of disability worldwide by 2020. This global burden emphasises not only the frequency of mood disorders but also their under-treatment, their recurrent nature and the high risk of suicide. All these factors highlight the need for more effective and acceptable treatments and so one of the aims of our Group is directly to develop and evaluate therapies for mood disorder. However discovering better treatment really requires a greater understanding of the nature of mood disorders. Therefore another key aim of the Group is to use a wide range of state-of- the-art methods to investigate what goes wrong in the brain in depression and what changes when antidepressant treatments are used. Such research can help discover not only the best targets for treatment but also the factors that lead to the disorder in the first place and that might be amenable to preventative measures. Our group brings together researchers with a special interest in mood disorders with the aim of using our combined expertise (which ranges from experimental studies in animals to brain imaging in patients and clinical trials) to design and carry out research projects that would be difficult for any of us to perform working alone. In the present grant we will make particular use of new techniques of magnetic brain imaging to learn more about the brain circuits that regulate emotional experience and the way in which they are modified by clinical mood disorders and their treatment.

Mood disorders are common and associated with very considerable morbidity and excess mortality. At present they are only poorly understood and partially treatable. The overarching objective of the Co-operative Group is to integrate clinical and laboratory neurobiological research to better understand the pathophysiology of mood disorders and thereby improve treatment and prognosis. The present application for renewed Co-operative status aims to build on the progress achieved during the tenure of our previous Co-operative Group, particularly in the integration of psychopharmacology with neuropsychological models of emotional processing. This has led to new ways of thinking about the psychological mechanisms that translate changes in the activity of relevant brain circuitry into clinical symptomatology and the therapeutic effects of psychotropic drugs. Our aim in the present Co-operative is to make full use of University facilities for functional magnetic resonance imaging to identify the neural substrates involved in these critical psychobiological interactions. As before our Co-operative will allow us to continue the vertical integration of our individual research efforts which range from molecular studies in animal and human tissue through PET imaging of molecular targets in patients, to growing expertise in clinical trials methodology. A particularly interesting finding derived from our previous Co-operative is the persistence of relevant neurobiological abnormalities in patients fully recovered from mood disorder and withdrawn from medication. We now have evidence of similar abnormalities in subjects who are at high risk of depression but who have not been depressed themselves. These abnormalities could represent an exciting opportunity to identify those at risk of mood disorder as well providing targets for preventative pharmacological or psychological treatment strategies. The ultimate aim of the Co-operative group therefore will be to use our growing knowledge of the neurobiology of depression and its treatment to provide realistic and effective preventative strategies for those at risk of recurrent mood disorder with its attendant personal and economic burdens.