What are the chances? - The search for biomarkers in bipolar disorders

A simple test based on a dried-blood-spot (DBS) sample to help diagnose or predict risk for bipolar disorder (BD). That’s what the research of Professor Sabine Bahn of the Centre for Neuropsychiatric Research at The University of Cambridge, UK hopes will become a reality to help reduce the misdiagnosis of BP.

Extensive research looking for neuroimaging biomarkers and genetic risk factors for BP has not, to date, produced anything akin to a diagnostic test for use in clinical practice. Such a test would be extremely useful. As Professor Bahn reminded delegates, BD is a condition that typically presents in ways that parallel the presentation of depression and is often misdiagnosed. Sometimes it can then take years before patients receive a correct diagnosis of BD  - during which time they may receive inappropriate treatments that can worsen outcomes and outlook. Given this state of affairs, Professor Bahn said the need for diagnostic aids and better biomarkers for BD is high.

Spot me

Blood biomarkers may not seem an obvious avenue for exploration in mental health disorders, but Professor Bahn described painstaking, targeted, proteomic research that is helping to uncover, discover and validate a diagnostic biomarker blood test panel for BD. Professor Bahn and her coworkers defined a mood-state-independent diagnostic biomarker panel for BD through a meta-analysis of case control studies from a number of centres, and then validated and applied the biomarker panel to test its pre-diagnostic utility in controls, people with BD and people with first-onset MDD. This exercise found that this 20-protein multiplex assay of serum samples had good predictive performance, able to differentiate misdiagnosed BD from first onset major depressive disorder (MDD).

Professor Bahn said the biomarker-based test also appears to work as a means of assaying and testing patient DBS samples – something that could make the test even simpler to use in clinical practice. She said that the study of DBS samples is linked with an initiative and study looking at DBS as a means to detect depression. According to Professor Bahn, DBS testing for BD, coupled with a 15 minute on-line questionnaire designed to elicit information relating to potential BD may offer a means to screen for and identify risks for both BD and MDD. She said that there are plans underway to develop an app based on the screening questionnaire that could also become a clinically useful tool for predicting future BD and finding undiagnosed BD.

Biomarker hurdles

Other speakers at the symposium, including Professor Marquis Vawter, Research Professor of Psychiatry, Psychiatry & Human Behaviour at the School of Medicine University of California, Irvine, USA, spoke of on-going endeavours in transcriptomics – looking at whole blood RNA biomarkers of BD. He said that such research is still only at the point of describing or finding potential biomarkers but is some way off being able to say what the pathophysiological relevance of such biomarkers may be.

Dr Tim Hahn, of the University of Frankfurt, Germany also highlighted the many hurdles and potential pitfalls in trying to find, study, validate and apply biomarkers as part of clinical practice. He reminded delegates that the ultimate goal in biomarker research would be to use biomarkers to provide truly individualized patient management -  to be able to match patients to the ‘perfect’ interventions to suit their own covariants. He also said that in BP the matter of differential diagnosis could be supported by finding suitable biomarkers. Dr Hahn said that medicine often relies on group data and in psychiatry descriptive data are also used to give hindsight and insight into the nature of a clinical condition. He said that ideally biomarkers should offer hindsight, insight and foresight. He described the complexities of developing predictive models for clinical diseases but said that machine algorithms can help in the construction, validation and clinical application and construction of useful biomarkers – be those based on imaging markers, proteomics and or neuropsychological markers.

The final presentation of the symposium by Dr Michèle Wessa, Johannes Gutenberg University Mainz in Germany described how refinements in neuropsychological testing may provide ways to follow, track and predict mood swings in BD. Dr Wessa said that automated approaches to neuropsychological testing could allow improved reliability.