TY - JOUR
T1 - Towards a blood-based diagnostic panel for bipolar disorder
AU - Haenisch, Frieder
AU - Cooper, Jason D
AU - Reif, Andreas
AU - Kittel-Schneider, Sarah
AU - Steiner, Johann
AU - Leweke, F Markus
AU - Rothermundt, Matthias
AU - van Beveren, Nico J M
AU - Crespo-Facorro, Benedicto
AU - Niebuhr, David W
AU - Cowan, David N
AU - Weber, Natalya S
AU - Yolken, Robert H
AU - Penninx, Brenda W J H
AU - Bahn, Sabine
PY - 2016/2
Y1 - 2016/2
N2 - 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.
AB - 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.
KW - Adult
KW - Biomarkers
KW - Bipolar Disorder
KW - Case-Control Studies
KW - Depressive Disorder, Major
KW - Diagnosis, Differential
KW - Female
KW - Humans
KW - Journal Article
KW - Male
KW - Meta-Analysis
KW - Middle Aged
KW - Research Support, Non-U.S. Gov't
KW - Schizophrenia
KW - Sensitivity and Specificity
U2 - https://doi.org/10.1016/j.bbi.2015.10.001
DO - https://doi.org/10.1016/j.bbi.2015.10.001
M3 - Article
C2 - 26441135
SN - 0889-1591
VL - 52
SP - 49
EP - 57
JO - Brain Behavior and Immunity
JF - Brain Behavior and Immunity
ER -