Cortical GABA and emotional processing in young people at risk of depression

Lead Research Organisation: University of Oxford
Department Name: Medical Sciences Division

Abstract

Clinical depression is a common and often a life-long condition that causes much distress and incapacity for sufferers and their families. Although there are some helpful treatments for depression it would be better to design interventions that could act at an early stage of the illness to prevent depression becoming chronic and disabling. For this we need to understand more about the factors that make people vulnerable to recurrent depression in the first place.

We have made some progress in this area by taking advantage of a new method of brain imaging called magnetic resonance imaging, which can measure the chemistry and functional activity of the brain by using strong magnetic fields. We have found for example, that people recovered from depression continue to have exaggerated responses in the brain to fearful facial expressions and that they have lowered levels of an important brain chemical messenger called GABA. However, we do not know if these changes pre-date the onset of the depressive illness or instead might be a consequence of the depression and its treatment.

The present study aims to answer this question by carrying out the same investigations in young people (aged 16-19 years) who have not been depressed themselves but who are at increased risk of depression through having a parent with depression. Magnetic resonance imaging lends itself to studies in young people because it is regarded as safe and non-invasive. If we find that young people at risk of depression have low brain GABA levels and increased brain responses to fearful facial expressions it will mean that these changes might be important in predisposing to the development of depression. We would then plan to find treatments that could resolve these changes in the hope that we might be able prevent or at least lower the risk of clinical depression occurring subsequently.

Technical Summary

It is increasingly recognised that in many patients depression is a recurrent illness with a poor long-term prognosis. Improvements in treatment and prevention are most likely to come from a better knowledge of pathophysiology, particularly in relation to the factors predisposing individuals to recurrent illness. In previous work we have found several persistent neurobiological abnormalities in recovered depressed patients which appear likely to increase the risk of recurrent illness. However, it is not clear whether these abnormalities pre-date the development of depression or are a consequence of recurrent illness and its treatment.

The present study aims to answer this question by studying young people who have no personal history of depression but who are at increased risk of illness though their family history. In these subjects we will use magnetic resonance imaging to examine cortical levels of the amino acid neurotransmitter, GABA, (with magnetic resonance spectroscopy) and the neural response to presentation of fearful facial expressions (with functional magnetic resonance imaging). We predict that like recovered depressed patients, young people at increased risk of depression will have low cortical GABA levels and increased amygdala responses to fearful facial expressions. Our current model of vulnerability to depression suggests that increased neural responses to fear in high-risk subjects are in part a consequence of lowered cortical GABA activity. We therefore predict that the two abnormalities will be inversely correlated in high-risk subjects.

The discovery of neurobiological abnormalities that pre-date the development of clinical illness in subjects at increased risk of depression will aid attempts at prevention of illness through early intervention. In addition, better knowledge of the pathophysiology of depression in young people could lead to improved treatment for depressive conditions in this age group.

Publications

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Description Oxford Neuroscience Festival 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Keynote talk at Oxford Neuroscience Festival attended by several hundred undergraduates and graduates.

Approaches by medical students to carry out electives in our laboratory.
Year(s) Of Engagement Activity 2012