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Transl Psychiatry. 2015 Jul 14;5:e599. doi: 10.1038/tp.2015.88.

Serum proteomic profiling of major depressive disorder.

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Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
Department of Chemical Engineering and Biotechnology, Institute of Biotechnology, University of Cambridge, Cambridge, UK.
Department of Psychiatry, University of Magdeburg, Magdeburg, Germany.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
1] Department of Psychiatry, University of Münster, Münster, Germany [2] Evangelisches Klinikum Niederrhein, Oberhausen, Germany.
1] Department of Chemical Engineering and Biotechnology, Institute of Biotechnology, University of Cambridge, Cambridge, UK [2] Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.


Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P < 0.05), whereas 10 partly overlapping markers differed significantly between rMDD cases and controls. Antidepressant medication use and comorbid anxiety status did not substantially impact on these findings. Sixteen of the cMDD-related markers had been assayed in the pooled validation cohorts, of which seven were associated with MDD. The analytes prominently associated with cMDD related to diverse cell communication and signal transduction processes (pancreatic polypeptide, macrophage migration inhibitory factor, ENRAGE, interleukin-1 receptor antagonist and tenascin-C), immune response (growth-regulated alpha protein) and protein metabolism (von Willebrand factor). Several proteins were implicated in depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology.

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