The Neurobiology of Mood Disorders

Lead Research Organisation: University of Oxford
Department Name: Psychiatry

Abstract

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.

Technical Summary

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.

Publications

10 25 50
 
Description BAP guideline on bipolar disorder
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact Improvement in the pharmacological management of bipolar disorder at a national level
 
Description MRC strategic review on Mental Health Research
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description NICE Panel on GAD
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact An evidence-based guideline on the treatment of generalised anxiety disorder. Improvements in clinical practice and management.
 
Description MRC Strategic Research Grant
Amount £350,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2008 
End 09/2011
 
Description MRC Strategic Research Grant
Amount £360,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2009 
End 07/2012
 
Description Pharmacology 
Organisation University of Oxford
Department Department of Pharmacology
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration on clinical translation of a lithium-mimetic
Collaborator Contribution basic animal studies which act as platform for human work.
Impact Grant from BBSRC
Start Year 2010
 
Title Emotional Test Battery 
Description A psychological test battery for the detection of psychotropically active drugs 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2010
Licensed Yes
Impact Industrial support including funding
 
Title Ebselen 
Description Antioxidant drug repurposed as lithium mimetic 
Type Therapeutic Intervention - Drug
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2013
Development Status Under active development/distribution
Impact Principle of drug repurposing for psychiatry. basic to clinical collaboration. New drug development for area of great unmet clinical need. 
 
Company Name P1Vital 
Description Interface between Oxford University Dept of Psychiatry and Pharmaceutical Industry. Applying novel methods of drug discovery to screen for new antidperessants at phase 1-2; http://www.p1vital.com/ 
Year Established 2006 
Impact Income generation from Industry through take up of screening studies
Website http://www.p1vital.com
 
Description Newspaper interviews and reports 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Catherine Harmer gave interviews to newspapers about her work on emotional processing and antidepressants

Further articles in the press
Year(s) Of Engagement Activity 2006,2008