The neural basis of treatment-induced remission in depression: an fMRI and pharmacoMRI study

Lead Research Organisation: University of Manchester
Department Name: Life Sciences

Abstract

We are trying to find out why some people with depression get better when treated with antidepressant drugs and why some fail to improve. Understanding this will allow us to be better able to match people with treatments that work for them, and to design better treatments.
A major gap in our understanding is how an emotional disorder like depression can be due to physical changes in the working of the brain, and how drug treatments can work on the brain to improve feelings
This research will help to bridge the gap by using brain imaging to identify abnormalities in the way the brain processes emotional cues in depression together with visualising the working of a key brain chemical, serotonin, that we know is involved in mood and depression.
We will test people with depression to find out how their brains’ reaction to emotional cues is altered and, using a new technique, how the serotonin system is working in parts of the brain that are responsible for emotion. Following treatment with an antidepressant we will test them again to find out how their improvement is linked to changes in emotional processing, and what predicts who will respond to the antidepressant.

Technical Summary

Depressed patients show abnormalities in emotional processing demonstrable using functional magnetic resonance imaging (fMRI) tasks, evidence of reduced brain serotonin function and structural brain abnormalities compared with non-depressed controls. This research will use functional magnetic resonance imaging (fMRI), connectivity analysis, structural MRI and imaging of serotonergic drug challenge (direct pharmacoMRI) to investigate abnormal emotional processing, the effects of antidepressant drug treatment and predictors of remission. This research is a natural extension to our published track?record in using Blood Oxygen Level Dependent (BOLD) fMRI and includes new pharmacoMRI techniques developed in our unit.
48 unmedicated depressed patients and 24 matched controls will receive fMRI tasks to probe key emotional/motivational processes shown to be abnormal in depression (face emotion, reward and loss and social affiliation) followed by connectivity analysis, structural brain scans and direct citalopram pharmacoMRI to image serotonin function. Patients will be then receive citalopram 20-40mg daily and have repeat testing of fMRI tasks, connectivity and brain structure after 8 weeks treatment with half of the controls retested after 8 weeks without treatment to control for repetition effects.
Our aim is to test the following general hypothesis: that depressive symptoms result from abnormal emotional processing arising from disrupted cortico-limbic connectivity which has a basis in altered 5-HT modulation and possibly structural abnormalities. Specific hypotheses are 1) that before treatment depressed patients will show abnormal neural patterns of response to the tasks, disrupted cortico-limbic connectivity and reduced ventral prefrontal cortex 5-HT function, 2) task-related and connectivity abnormalities will be rectified by treatment in remitters after treatment and 3) increased task-related amygdala activation and relatively preserved serotonin function pre-treatment will predict remission after treatment.

Publications

10 25 50
 
Description P1Vital; Sunovion Ltd
Amount £450,000 (GBP)
Organisation P1vital Consortium 
Sector Private
Country United Kingdom
Start 08/2014 
End 03/2016
 
Description BBC New Magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed by BBC journalist, Tara McKelvey in context of Radio programme by Will Self on the treatment of Depression 'The Prozac Economy'

None direct
Year(s) Of Engagement Activity 2013
URL http://www.bbc.co.uk/news/magazine-22040733
 
Description Cheltenham Science festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presented as part of a general talk on imaging emotion by Dr Rebecca Elliott

None specific
Year(s) Of Engagement Activity 2010
 
Description Contribution to TV programme on depression (BBC NI) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I was interviewed by a TV team from NI and presented research findings that appeared in a film on the nature of Depression, screened in Northern Ireland

Strong anti-stigma message given
Year(s) Of Engagement Activity 2013
URL http://www.bbc.co.uk/programmes/p018r6wl