Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers

Erin M. van Buel; Marcus J.M. Meddens; Eduard A. Arnoldussen; Edwin R. van den Heuvel; Willem C. Bohlmeijer; Johan A. den Boer; Anna Muller Kobold; Leandra J.M. Boonman-de Winter; Dirk van Rumpt; Lambertus F.J. Timmers; Mattheus F.A. Veerman; Johannes S. Kamphuis; Anatoliy V. Gladkevich; Robert A. Schoevers; Paul G.M. Luiten; Ulrich L.M. Eisel; Fokko J. Bosker; Hans C. Klein

doi:10.1016/j.jpsychores.2019.109796

Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers

Erin M. van Buel
, Marcus J.M. Meddens
, Eduard A. Arnoldussen
, Edwin R. van den Heuvel
, Willem C. Bohlmeijer
, Johan A. den Boer
, Anna Muller Kobold
, Leandra J.M. Boonman-de Winter
, Dirk van Rumpt
, Lambertus F.J. Timmers
, Mattheus F.A. Veerman
, Johannes S. Kamphuis
, Anatoliy V. Gladkevich
, Robert A. Schoevers (Corresponding author)
, Paul G.M. Luiten
, Ulrich L.M. Eisel
, Fokko J. Bosker
, Hans C. Klein

Research output: Contribution to journal › Article › Academic › peer-review

15 Citations (Scopus)

Abstract

Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the “bio depression score”). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P <.001), in serum (P =.02) and in the combined serum plus urine result (P <.001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.

Original language	English
Article number	109796
Number of pages	8
Journal	Journal of Psychosomatic Research
Volume	125
DOIs	https://doi.org/10.1016/j.jpsychores.2019.109796
Publication status	Published - 1 Oct 2019

Funding

This work is based on a grant called PIDON originating from Dutch governmental institutions (provinces Gelderland and Overijssel, registered under grant number PID_09_02/120329 ), in which Brainlabs, University of Groningen and University Medical Center Groningen participated. The PIDON grant covered the activities of literature search, study design, patient inclusions, laboratory analysis and data reduction. Appendix A

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Biomarker panel
Biomarkers
ELISA
Major depressive disorder
Permutation analysis
Urine

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10.1016/j.jpsychores.2019.109796

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van Buel, E. M., Meddens, M. J. M., Arnoldussen, E. A., van den Heuvel, E. R., Bohlmeijer, W. C., den Boer, J. A., Muller Kobold, A., Boonman-de Winter, L. J. M., van Rumpt, D., Timmers, L. F. J., Veerman, M. F. A., Kamphuis, J. S., Gladkevich, A. V., Schoevers, R. A., Luiten, P. G. M., Eisel, U. L. M., Bosker, F. J., & Klein, H. C. (2019). Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers. Journal of Psychosomatic Research, 125, Article 109796. https://doi.org/10.1016/j.jpsychores.2019.109796

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title = "Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers",

abstract = "Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the “bio depression score”). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P <.001), in serum (P =.02) and in the combined serum plus urine result (P <.001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.",

keywords = "Biomarker panel, Biomarkers, ELISA, Major depressive disorder, Permutation analysis, Urine",

author = "\{van Buel\}, \{Erin M.\} and Meddens, \{Marcus J.M.\} and Arnoldussen, \{Eduard A.\} and \{van den Heuvel\}, \{Edwin R.\} and Bohlmeijer, \{Willem C.\} and \{den Boer\}, \{Johan A.\} and \{Muller Kobold\}, Anna and \{Boonman-de Winter\}, \{Leandra J.M.\} and \{van Rumpt\}, Dirk and Timmers, \{Lambertus F.J.\} and Veerman, \{Mattheus F.A.\} and Kamphuis, \{Johannes S.\} and Gladkevich, \{Anatoliy V.\} and Schoevers, \{Robert A.\} and Luiten, \{Paul G.M.\} and Eisel, \{Ulrich L.M.\} and Bosker, \{Fokko J.\} and Klein, \{Hans C.\}",

year = "2019",

month = oct,

day = "1",

doi = "10.1016/j.jpsychores.2019.109796",

language = "English",

volume = "125",

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van Buel, EM, Meddens, MJM, Arnoldussen, EA, van den Heuvel, ER, Bohlmeijer, WC, den Boer, JA, Muller Kobold, A, Boonman-de Winter, LJM, van Rumpt, D, Timmers, LFJ, Veerman, MFA, Kamphuis, JS, Gladkevich, AV, Schoevers, RA, Luiten, PGM, Eisel, ULM, Bosker, FJ & Klein, HC 2019, 'Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers', Journal of Psychosomatic Research, vol. 125, 109796. https://doi.org/10.1016/j.jpsychores.2019.109796

TY - JOUR

T1 - Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers

AU - van Buel, Erin M.

AU - Meddens, Marcus J.M.

AU - Arnoldussen, Eduard A.

AU - van den Heuvel, Edwin R.

AU - Bohlmeijer, Willem C.

AU - den Boer, Johan A.

AU - Muller Kobold, Anna

AU - Boonman-de Winter, Leandra J.M.

AU - van Rumpt, Dirk

AU - Timmers, Lambertus F.J.

AU - Veerman, Mattheus F.A.

AU - Kamphuis, Johannes S.

AU - Gladkevich, Anatoliy V.

AU - Schoevers, Robert A.

AU - Luiten, Paul G.M.

AU - Eisel, Ulrich L.M.

AU - Bosker, Fokko J.

AU - Klein, Hans C.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the “bio depression score”). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P <.001), in serum (P =.02) and in the combined serum plus urine result (P <.001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.

AB - Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the “bio depression score”). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P <.001), in serum (P =.02) and in the combined serum plus urine result (P <.001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.

KW - Biomarker panel

KW - Biomarkers

KW - ELISA

KW - Major depressive disorder

KW - Permutation analysis

KW - Urine

UR - https://www.scopus.com/pages/publications/85071260987

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DO - 10.1016/j.jpsychores.2019.109796

M3 - Article

C2 - 31470255

AN - SCOPUS:85071260987

SN - 0022-3999

VL - 125

JO - Journal of Psychosomatic Research

JF - Journal of Psychosomatic Research

M1 - 109796

ER -

Major depressive disorder is associated with changes in a cluster of serum and urine biomarkers

Abstract

Funding

UN SDGs

Keywords

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