TY - JOUR

T1 - A multisystem composite biomarker as a preliminary diagnostic test in bipolar disorder

AU - Munkholm, K.

AU - Vinberg, M.

AU - Pedersen, B. K.

AU - Poulsen, H. E.

AU - Ekstrøm, C. T.

AU - Kessing, L. V.

PY - 2019

Y1 - 2019

N2 - Objective: Diagnosis and management of bipolar disorder (BD) are limited by the absence of available laboratory tests. We aimed to combine data from different molecular levels and tissues into a composite diagnostic and state biomarker. Methods: Expression levels of 19 candidate genes in peripheral blood, plasma levels of BDNF, NT-3, IL-6 and IL-18, leukocyte counts, and urinary markers of oxidative damage to DNA and RNA were measured in 37 adult rapid-cycling patients with BD in different affective states during a 6- to 12-month period and in 40 age- and gender-matched healthy individuals in a longitudinal, repeated measures design comprising a total of 211 samples. A composite biomarker was constructed using data-driven variable selection. Results: The composite biomarker discriminated between patients with BD and healthy control individuals with an area under the receiver operating characteristic curve (AUC) of 0.83 and a sensitivity of 73% and specificity of 71% corresponding with a moderately accurate test. Discrimination between manic and depressive states had a moderate accuracy, with an AUC of 0.82 and a sensitivity of 92% and a specificity of 40%. Conclusion: Combining individual biomarkers across tissues and molecular systems could be a promising avenue for research in biomarker models in BD.

AB - Objective: Diagnosis and management of bipolar disorder (BD) are limited by the absence of available laboratory tests. We aimed to combine data from different molecular levels and tissues into a composite diagnostic and state biomarker. Methods: Expression levels of 19 candidate genes in peripheral blood, plasma levels of BDNF, NT-3, IL-6 and IL-18, leukocyte counts, and urinary markers of oxidative damage to DNA and RNA were measured in 37 adult rapid-cycling patients with BD in different affective states during a 6- to 12-month period and in 40 age- and gender-matched healthy individuals in a longitudinal, repeated measures design comprising a total of 211 samples. A composite biomarker was constructed using data-driven variable selection. Results: The composite biomarker discriminated between patients with BD and healthy control individuals with an area under the receiver operating characteristic curve (AUC) of 0.83 and a sensitivity of 73% and specificity of 71% corresponding with a moderately accurate test. Discrimination between manic and depressive states had a moderate accuracy, with an AUC of 0.82 and a sensitivity of 92% and a specificity of 40%. Conclusion: Combining individual biomarkers across tissues and molecular systems could be a promising avenue for research in biomarker models in BD.

KW - biomarkers

KW - bipolar disorder

KW - blood

KW - gene expression

KW - urine

U2 - 10.1111/acps.12983

DO - 10.1111/acps.12983

M3 - Journal article

C2 - 30383306

AN - SCOPUS:85057553079

VL - 139

SP - 227

EP - 236

JO - Acta Psychiatrica Scandinavica

JF - Acta Psychiatrica Scandinavica

SN - 0001-690X

IS - 3

ER -