Use of biomarkers to detect pre-symptomatic medical co-morbidity in young people at familial risk of depression

Lead Research Organisation: University of Oxford
Department Name: Psychiatry


Clinical depression often develops in young people and can then recur over a lifetime. Once established, depression puts people at increased risk of other medical conditions such as diabetes, heart disease and memory problems. In our study we wish to explore the idea that depression and these other medical conditions are linked by increased secretion of a stress hormone called cortisol. We believe that the increase in cortisol secretion happens for many years before the illnesses actually occur. Increased cortisol secretion could theoretically account for why people become depressed and then develop the related medical conditions. If this is the case it might be possible to devise new methods of treatment which would prevent the development of both depression and its medical complications by lowering cortisol before the illnesses have become apparent.
We have recently found that young people at increased risk of depression through having a family history of the illness secrete too much cortisol before they have any evidence of depression or any other medical illness. If our idea is correct then we would expect the same young people to have evidence of abnormalities suggesting they are at risk of the medical conditions linked to depression. For example, they may show decreased efficiency of handling glucose (vulnerability to diabetes), changes in the elasticity of blood vessels (vulnerability to blood vessel disease) and smaller volume of a brain structure called the hippocampus (vulnerability to memory problems). This is what we will test in the present study.

Technical Summary

Recurrent depression is a common condition with high morbidity often beginning in young adulthood and extending over the lifespan. Established depression is associated with several co-morbid general medical conditions, particularly obesity, diabetes, cardiovascular disease and cognitive decline. Pathophysiologically both depression and many of its medical co-morbidities share a liability to increased activity of the hypothalamo-pituitary-adrenal (HPA) axis. Our group has recently shown that increased waking salivary cortisol secretion has trait characteristics in people vulnerable to depression and indeed young people at increased familial risk of the illness hypersecrete cortisol despite never having experienced significant depressive symptomatology. The aim of the current proposal is to test the hypothesis that young people at increased familial risk of depression will also demonstrate abnormal markers of the associated medical conditions, specifically decreases in insulin sensitivity, endothelial function, declarative memory and hippocampal volume. Positive findings from this study could lead to a reconceptualisation of depression and its co-morbidities as responses within individuals to many years of asymptomatic but persistently increased cortisol secretion. This could lead to early intervention strategies targeting the activity of the HPA axis which could help prevent the eventual development of several highly burdensome clinical disorders


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Mannie Z (2014) Decision making in young people at familial risk of depression in Psychological Medicine

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Mannie ZN (2013) Cardiovascular and metabolic risk profile in young people at familial risk of depression. in The British journal of psychiatry : the journal of mental science

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Norbury R (2011) Imaging vulnerability for depression. in Molecular psychiatry

Description Aldosterone in metabolic complications of depression 
Organisation University of Dundee
Department Division of Cardiovascular and Diabetes Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Identification of raised aldosterone levels in young people at familial risk of depression
Collaborator Contribution World leading expertise in aldosterone and medicine. Measurement of aldosterone
Impact Grant application to MRC EMM csheme
Start Year 2013
Description Oxford Biomedical Research Centre 
Organisation University of Oxford
Department Nuffield Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Study of the effect of interferon alpha on brain neurochemistry using MRS
Collaborator Contribution provision of patients and immunological expertise
Impact papers submitted fro publication
Start Year 2009
Description Oxford Cardiovascular Clinical Research Facility 
Organisation University of Oxford
Department Oxford Cardiovascular Clinical Research Facility (CCRF)
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration to study cardiovascular risk factors in young people at increased risk of depression
Collaborator Contribution Expertise in design of cardiovascular studies and their interpretation in young at-risk individuals
Impact Analysis of results in progress
Start Year 2009
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