Frieder Haenisch1, Jason D Cooper1, Andreas Reif2, Sarah Kittel-Schneider2, Johann Steiner3, F Markus Leweke4, Matthias Rothermundt5, Nico J M van Beveren6, Benedicto Crespo-Facorro7, David W Niebuhr8, David N Cowan8, Natalya S Weber8, Robert H Yolken9, Brenda W J H Penninx10, Sabine Bahn11. 1. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom. 2. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Hospital Frankfurt, Germany. 3. Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Magdeburg, Magdeburg, Germany. 4. Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany. 5. Department of Psychiatry, University of Münster, Germany. 6. Department of Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands. 7. CIBERSAM, University Hospital Marqués de Valdecilla, University of Cantabria - IDIVAL, Department of Psychiatry, Santander, Spain. 8. Walter Reed Army Institute of Research, Silver Spring, MD, USA. 9. Johns Hopkins University School of Medicine, Baltimore, MD, USA. 10. Department of Psychiatry, EMGO Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 11. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom. Electronic address: sb209@cam.ac.uk.
Abstract
BACKGROUND: Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD. METHODS AND FINDINGS: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies. We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC)⩾0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel. CONCLUSIONS: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.
BACKGROUND:Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD. METHODS AND FINDINGS: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies. We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC)⩾0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDDpatients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel. CONCLUSIONS: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.
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