Depression Therapeutics

Oxford with Universities of Birmingham and Reading

To use human neurocognitive models to identify and develop new and improved treatments for depression

Depression is a leading cause of disability. However, current treatments leave many patients facing incomplete recovery and there is an important need to increase the speed of development of novel therapies and support greater personalisation in their use.

The application of innovative neuroscience-based approaches to the treatment of depression has been limited by the inability of animal models to predict clinical effects. Human neurocognitive models of antidepressant action can bridge this translational gap allowing rapid study of novel compounds in both healthy participants and people with depression.

This Theme will help deliver the next-generation fast-acting antidepressant treatments and extend the approach to improve treatment for young people with depression and anxiety. This will involve work with industry (through an Experimental Medicine in Industry Partnership), clinical, academic and patient partners.

Mood disorders clinics will be set up, and protocols harmonised, in Oxford and Birmingham. This will facilitate clinical excellence and increase the opportunity for research participation across diverse populations.

The work has 5 Sub-Themes:

Sub-Theme 1 focuses on the neurocognitive changes of fact-acting antidepressants such as ketamine, particularly on key depressive symptoms such as anhedonia and persistent negative memories. We will use ketamine to generate experimental medicine models of fast acting antidepressant action in humans. These models will allow the rapid testing and roll out of next generation treatments.

Sub-Theme 2 will assess the therapeutic potential of repurposed anti-inflammatory immune modulators in human neurocognitive models, in conjunction with EMIP members and academic colleagues in the Inflammation Theme at the OUH BRC.

Sub-Theme 3 will use computational models to refine understanding to improve prediction of treatment effects for clinical anhedonia.

Sub-Theme 4 will develop human models to study the therapeutic mechanisms of antidepressant treatment in young people with depression.

Sub-Theme 5 will build on findings from the above themes to formulate and test novel approaches for depression focusing on combination approaches of different treatment modalities.

This Theme continues ongoing BRC work where PPIEP has been embedded in all stages of the research cycle including agenda setting, protocol design, data interpretation and dissemination.  The team is committed to increasing the representation of marginalised groups and have broadened participant recruitment methods and expanded geographical reach through the partnership with Birmingham.

For more information on PPIEP contact: amy.gillespie@psych.ox.ac.uk

Increasing the training of psychiatrists in research will be undertaken by establishing joint posts with Oxford Health NHS FT.  The Theme is committed to enhancing capacity building and career development as part of its work with early career researchers involved in the leadership of sub-Themes and mentored by senior clinical and academic staff.