A cognitive vaccine for depression: assessment using neurobiological outcomes in experimental medicine models

Lead Research Organisation: University of Oxford
Department Name: Psychiatry

Abstract

One of the most debilitating aspects of depression is that it tends to recur in the same people over and over again. In fact if you have had one episode of depression there is an 80% chance you?ll have at least one further episode in your life, and you may have many more. The recurrent nature of depression suggests that certain individuals have a constitutional tendency or ?vulnerability factor? to develop the illness. It?s crucial that we understand what these may be; as if we can treat them we should be able to prevent the depression from recurring. Such a treatment could be thought of as a ?vaccine? against depression.
A strong contender for a vulnerability factors for depression is the way peoples? brains handle emotional information. For example there is evidence that people who have been depressed pay more attention to negative information.
This processing style would be a particularly promising target for treatment as there is already a simple method for changing it; the ?cognitive bias modification of attention? task (CBMa). CBMa is a simple, computer based task that helps people get in the habit of ignoring negative information. We think that the CBMa task may work as a ?vaccine? against depression.
In this project we are going to assess whether it looks like CBMa will prevent recurrent depression. To do this we?re going to perform three studies. All three studies will compare the effects of CBMa with a similar, but inactive, control procedure in people who have previously been depressed. Study 1 will look at the basic effect of CBMa and will provide information about how often it should be carried out. Studies 2 and 3 will gauge how effective CBMa is likely to be in preventing depression by measuring how it affects a range of biological abnormalities which tend to occur in people who have repeated depression. Specifically we will measure the effects of CBMa on:

? How much of a hormone called cortisol participants have in their saliva

? Which areas of participants? brains are activated by negative pictures

? Whether participants? mood drops after the level of serotonin in their brain is reduced using the ?Acute Trypotophan Depletion? procedure.

All of these measures will give us information on whether CBMa is likely to reduce recurrence of depression and whether we?re ready to try it out in large scale clinical trials.

Technical Summary

Depression is overwhelmingly a recurrent disorder; a patient experiencing their first episode has an 80% chance of recurrence in their lifetime. This pattern of recurrence strongly suggests that certain individuals possess stable vulnerability factors that predispose them to develop the disorder. Treatments which target these vulnerability factors should act like a vaccine, reducing the chance of the illness recurring. The current application therefore considers whether a cognitive manipulation which targets dysfunctional attentional systems in patients vulnerable to depression is likely to represent an effective ?vaccine? against depression. The efficacy of the manipulation will be assessed using neurobiological surrogate markers of vulnerability to depression and the susceptibility of participants to pharmacological induction of depressed mood.

The procedure to be assessed is a novel, computer based intervention designed specifically to alter attentional bias, the cognitive bias modification of attention (CBMa) task. This will be achieved in a series of three studies. Study 1 will deploy and optimise the CBMa procedure in a previously depressed population. Studies 2 and 3 will assess the efficacy of CBMa in previously depressed participants using three well-validated neurobiological surrogate markers including amygdala responses to threat, early morning cortisol response and response to pharmacological induction of depression with tryptophan depletion. All studies will employ a randomised, between subjects design with participants being allocated to either an active CBMa or a control group.

By using sensitive biological markers in an experimental model of vulnerability to depression this project will provide proof of concept data on the CBMa procedure before deploying it in larger scale clinical trials. It will also provide the opportunity to explore the interaction of cognitive and biological vulnerability factors relevant to depression. The results from the proposed series of studies would therefore have implications both for the treatment of this debilitating disorder and for our understanding of the cognitive and biological processes underlying it.

Publications


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Browning M (2011) Using an experimental medicine model to explore combination effects of pharmacological and cognitive interventions for depression and anxiety. in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
 
Description Wellcome Trust Strategic Award
Amount £1,500,000 (GBP)
Organisation The Wellcome Trust Ltd 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2014 
End 06/2016
 
Description UWA 
Organisation University of Western Australia
Country Australia, Commonwealth of 
Sector Academic/University 
PI Contribution We are providing expertise and research experience in developing novel experiential (and possibly clinical) interventions
Collaborator Contribution The collaborators have obtained specific research funding to encourage collaboration between our department and theirs. This will be used to fund sabbatical visits with a view to developing the techniques used in this grant.
Impact An applicant on the grant is currently visiting the University of Western Australia on the first of these planned visits
Start Year 2011
 
Description Umea 
Organisation Umea University
Department Psychology Umea
Country Sweden, Kingdom of 
Sector Academic/University 
PI Contribution We have provided intellectual support in developing the clinical intervention used in the study.
Collaborator Contribution The collaborators have recently deployed a version of the intervention tested in this grant on patients with social anxiety
Impact Data have been collected from 130 patients with social phobia. This is currently being analysed
Start Year 2011
 
Description Greener Mental Health Summit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/parliamentarians
Results and Impact London, 2010: Using Attentional Training as a "Cognitive Vaccine" in Previously Depressed Patients.
Healthcare professionals, commissioners and third sector workers attended a series of talks about novel programs which had the potential to reduce the environmental impact of mental health care activities.

Published statement from attendees for "Strong support and 'seed funding' for research necessary to create environmentally sustainable mental health services" including the techniques used in the current grant.
Year(s) Of Engagement Activity 2010
 
Description Press Briefing 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Press Briefing in science media centre.

Article appeared in BBC news online http://news.bbc.co.uk/1/hi/health/8304782.stm
Year(s) Of Engagement Activity 2009
URL http://news.bbc.co.uk/1/hi/health/8304782.stm