, Volume 233, Issue 15–16, pp 3051–3059 | Cite as

Molecular serum signature of treatment resistant depression

  • Tillmann Ruland
  • Man K. Chan
  • Pawel Stocki
  • Laura Grosse
  • Matthias Rothermundt
  • Jason D. Cooper
  • Volker Arolt
  • Sabine Bahn
Original Investigation



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.


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).


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.


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.


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.


Treatment resistant depression Mass spectrometry Staging Serum 



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.

Compliance with ethical standards

Conflict of interest

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.

Supplementary material

213_2016_4348_MOESM1_ESM.pdf (200 kb)
ESM 1 (PDF 199 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Tillmann Ruland
    • 1
    • 3
  • Man K. Chan
    • 3
  • Pawel Stocki
    • 3
  • Laura Grosse
    • 1
    • 2
  • Matthias Rothermundt
    • 1
  • Jason D. Cooper
    • 3
  • Volker Arolt
    • 1
  • Sabine Bahn
    • 3
  1. 1.Mood and Anxiety Disorders Research Unit, Department of Psychiatry and PsychotherapyUniversity of MuensterMuensterGermany
  2. 2.Radiology Morphological SolutionsRotterdamThe Netherlands
  3. 3.Department of Chemical Engineering and BiotechnologyUniversity of CambridgeCambridgeUK

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