Neurobiology of resilience to depression

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences


Depression is the most common mental health problem, affecting as many as 1 in 5 people during their lives. It is a significant economic and social burden as well as causing distress to affected individuals and their families. Although a number of factors are involved in causing depression, we know that experiencing stressful life events triggers many depressive episodes. By contrast, there are individuals who can experience large amounts of life stress without becoming depressed, a trait called resilience. We know very little about the reasons why some people are more resilient than others. This research will use modern techniques to investigate whether there is an identifiable brain basis for resilience. If a distinct profile associated with resilience exists, this has potential implications for developing therapeutic approaches that could help prevent people with major life stress from developing depression.

Technical Summary

Resilience in the face of stressful life events is an important concept for understanding and managing depression. Promoting resilience in people at risk of depression has implications for prevention of depressive episodes. This proposal aims to use neuropsychological and neuroimaging techniques to characterise the neurobiological profile associated with resilient individuals. We will capitalise on our existing database of 2004 subjects recruited in the Manchester community with depression history and life stress information recorded. Using this database we will recruit groups of subjects with and without significant life stress and with and without depression. More detailed interviews will allow us to characterize five groups with differing degrees of resilience and vulnerability to life stress. 40 subjects in each group will complete a thorough neuropsychological assessment using tests specifically targeting putative resilience mechanisms identified in research at the University of Cambridge. A subset of 20 subjects from each group will be scanned using functional magnetic resonance imaging (fMRI) with cognitive challenge tasks. These tasks have been chosen to probe both specific cognitive processes and the functioning of specific brain regions (limbic system and medial prefrontal cortex). Finally we will perform a pharmacological challenge in resilient and vulnerable groups, using acute tryptophan depletion to lower brain serotonin. Following this manipulation, subjects will undergo the same neuropsychological and neuroimaging procedures to determine whether resilient responses are modulated by brain serotonin levels. Planned comparisons between the groups will allow us to test hypotheses about the cognitive mechanisms of resilience and determine whether there is a distinct neurobiological profile associated with this trait. This would represent a potential biomarker for pharmacological and psychological interventions in individuals at risk for depression due to significant life stress.
Description BBC Radio 4 interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Th interview will form part of two programmes to be broadcast on BBC radio 4 and BBC world service (with online podcast) in December 2011

Year(s) Of Engagement Activity 2011
Description MQ Mental Health meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact 2018 MQ Mental Health Science Meeting
Year(s) Of Engagement Activity 2018
Description School visits (Cheshire, Manchester and Bolton) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Six events, all using key examples from work supported by 2 MRC grants (as assigned).

In Manchester 120 year 11 pupils attended a talk on brain imaging and mental health and asked questions, discussed issues afterwards. The same talk to Bolton schools was attended by 60 year 11 students. In Cheshire, 20 A level Psychology students attended an hour long talk on this topic on three successive occasions and 16 of them subsequently visited me and post-docs working on these projects at work to hear more about the research on an individual basis.

Several A level students reported that the visit helped them decide to choose to apply to university to study psychology/neuroscience.
Year(s) Of Engagement Activity 2011,2012,2013,2014