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Biomarkers for depression – light at the end of the tunnel?

18 Feb, 2014

Depression: Nanette Hoogslag, Wellcome Images New research published this week focuses on an issue central to mental health research – the identification of a physiological biomarker for depression. Scientists in Cambridge looked at teenagers and found that boys with a particular marker were at a significantly greater risk of developing depression later in life than those without it. Cynthia Joyce, Chief Executive of the mental health charity MQ: Transforming Mental Health gives us some context to the research and explains why biomarkers for depression are so sought after.

It is sobering to realise that major research efforts around the world have been unsuccessful in their search for genetic or body fluid measures that might tell us who might be at risk of, much less confirm the presence of depression.  The lack of good diagnostic and prognostic markers has stymied efforts to find better treatments and preventive interventions, as well as hindering work to refine our definitions of depression.  Our lack of success in this area undoubtedly reflects the complexity of the disorder as well as a deficiency of tools and technologies to help solve the problem.

Owens and colleagues have demonstrated that when measures of self-reported symptoms of depression and early morning cortisol (stress hormone) levels are considered together in adolescents, the combination can be more sensitive than the individual items alone.  This finding sets the stage for conducting new kinds of depression studies in the future.

This finding is important because while any number of candidate biomarkers (genes, proteins, physical traits, symptoms) have been identified for depression, the associations have proven difficult to pin down and validate as bona fide markers. A systematic approach to the challenge is much needed and is becoming more feasible thanks to collaborative efforts at the regional, national and global level.  Collaborations like the Psychiatric Genetics Consortium for example, are compiling ever-larger sample sizes of genetic data in a brute force effort to uncover genes associated with the spectrum of mental health disorders.  Meanwhile the search for biomarkers in body fluids is now being coordinated, albeit at a smaller level through efforts like the UK Biobank (supported by the Wellcome Trust and other funders), where markers of depression and bipolar disorder as well as other co-morbid conditions are under study.

This proof of concept study represents a real advance for the study of depression.  The combined “bio-behavioural” marker will enable more comprehensive study of how depression evolves over time, and perhaps even how we might prevent it.

The markers will allow sophisticated clinical trial designs where participants can be stratified by the presence of the biomarker to allow a closer look at treatment effects, in the same way cancer studies are now conducted.  This could mean smaller, shorter trials in the future – and perhaps lead to even better treatments.  Of course there is more work to be done to better understand this new biomarker combination.  For instance, it will be helpful to know if there is a threshold for cortisol levels associated with risk – and whether or not there are discrete questions in the standard mood and feeling questionnaire that may predict risk even better.  But these are good questions to have at a time when the need for biomarkers is so great.

It is important to note that the newly reported biomarker is actually a combination of behavioural and biological measures, as this approach may be key to the discovery and confirmation of other new markers for mental illness.  There is increasing evidence that depression and other mental illnesses may share underlying biological and psychological mechanisms – suggesting that we may want to consider combinations of markers as inevitable too.

What is clearly important at this stage of the game is to use all the resources in our power to get our markers right so that we can truly advance both care and our understanding of depression.   One way we might be able to do this is by asking biological and psychological scientists to work more closely together toward this goal, and indeed the new charity MQ is preparing to launch a funding call precisely along these lines.

Cynthia Joyce, Chief Executive, MQ: Transforming Mental Health

(Owens et al; 18 Feb PNAS 2014)

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