title: Towards a blood-based diagnostic panel for bipolar disorder.
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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Frieder
authors.initials: F
authors.lastname: Haenisch
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Hospital Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Hospital Frankfurt, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Magdeburg, Magdeburg, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.affiliation: Department of Psychiatry, University of Münster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothermundt
authors.affiliation: Department of Psychiatry, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Nico J M
authors.initials: NJM
authors.lastname: van Beveren
authors.affiliation: CIBERSAM, University Hospital Marqués de Valdecilla, University of Cantabria - IDIVAL, Department of Psychiatry, Santander, Spain.
authors.forename: Benedicto
authors.initials: B
authors.lastname: Crespo-Facorro
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Niebuhr
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Cowan
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Weber
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.affiliation: Department of Psychiatry, EMGO Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BWJH
authors.lastname: Penninx
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom. Electronic address: sb209@cam.ac.uk.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000175:diagnosis*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers
keywords: Biomarker; Bipolar disorder; Diagnostic test; Differential diagnosis; Multiplex immunoassay