Open Access

Frieder Haenisch, Jason D. Cooper, Andreas Reif, Sarah Kittel-Schneider, Johann Steiner, F. Markus Leweke, Matthias Rothermundt, Nico J. M. van Beveren, Benedicto Crespo-Facorro, David W. Niebuhr, David N. Cowan, Natalya S. Weber, Robert H. Yolken, Brenda W. J. H. Penninx, Sabine Bahn

• Highlights • A panel of 20 biomarkers was identified capable of differentiating BD patients from controls. • Excellent discrimination between established BD patients and controls. • Good to excellent discrimination between misdiagnosed BD patients and first onset MDD patients. • Fair to good discrimination between pre-diagnostic BD patients and controls. • Study demonstrates the potential utility of a protein biomarker panel as a diagnostic test for BD. 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.