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Molecular serum signature of treatment resistant depression

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Abstract

Rationale

A substantial number of patients suffering from major depressive disorder (MDD) do not respond to multiple trials of anti-depressants, develop a chronic course of disease and become treatment resistant. Most of the studies investigating molecular changes in treatment-resistant depression (TRD) have only examined a limited number of molecules and genes. Consequently, biomarkers associated with TRD are still lacking.

Objectives

This study aimed to use recently advanced high-throughput proteomic platforms to identify peripheral biomarkers of TRD defined by two staging models, the Thase and Rush staging model (TRM) and the Maudsley Staging Model (MSM).

Methods

Serum collected from an inpatient cohort of 65 individuals suffering from MDD was analysed using two different mass spectrometric-based platforms, label-free liquid chromatography mass spectrometry (LC-MSE) and selective reaction monitoring (SRM), as well as a multiplex bead based assay.

Results

In the LC-MSE analysis, proteins involved in the acute phase response and complement activation and coagulation were significantly different between the staging groups in both models. In the multiplex bead-based assay analysis TNF-α levels (log(odds) = −4.95, p = 0.045) were significantly different in the TRM comparison.

Using SRM, significant changes of three apolipoproteins A–I (β = 0.029, p = 0.035), M (β = −0.017, p = 0.009) and F (β = −0.031, p = 0.024) were associated with the TRM but not the MSM.

Conclusion

Overall, our findings suggest that proteins, which are involved in immune and complement activation, may represent potential biomarkers that could be used by clinicians to identify high-risk patients. Nevertheless, given that the molecular changes between the staging groups were subtle, the results need to be interpreted cautiously.

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Acknowledgments

This study was supported by EU-FP7-HEALTH-F2-2008-222963 “MOODINFLAME” and by EU-FP7-PEOPLE-2009-IAPP “PSYCH-AID”. These supporters had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report and in the decision to submit the paper for publication.

Drs. Chan, Cooper and Prof. Bahn were also supported by grants from the Stanley Medical Research Institute (no. 07R-1888) and the EU-FP7 SchizDX.

Author contributions

TR and MKC designed the study and are responsible for the statistical analyses and the first draft of the manuscript. VA, MR, LS and TR were responsible for recruitment and clinical characterization of the patients; TR and PS performed the laboratory work. JC supervised the statistical analyses. VA and SB supervised the study and were involved in the design of the study. All authors contributed to and have approved the final manuscript.

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    Authors and Affiliations

    1. Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany

      Tillmann Ruland, Laura Grosse, Matthias Rothermundt & Volker Arolt

    2. Radiology Morphological Solutions, Rotterdam, The Netherlands

      Laura Grosse

    3. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK

      Tillmann Ruland, Man K. Chan, Pawel Stocki, Jason D. Cooper & Sabine Bahn

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    1. Tillmann Ruland
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    Correspondence to Tillmann Ruland.

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    Prof. Bahn is a director of Psynova Neurotech Ltd. Dr. Cooper is a consultant for Psynova Neurotech Ltd. No other authors report potential conflict of interest.

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    Tillmann Ruland and Man K. Chan contributed equally to this work.

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    Ruland, T., Chan, M.K., Stocki, P. et al. Molecular serum signature of treatment resistant depression. Psychopharmacology 233, 3051–3059 (2016). https://doi.org/10.1007/s00213-016-4348-0

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