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.
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.
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.