Ruland, T;
Chan, MK;
Stocki, P;
Grosse, L;
Rothermundt, M;
Cooper, JD;
Arolt, V;
(2016)
Molecular serum signature of treatment resistant depression.
Psychopharmacology
, 233
(15-16)
pp. 3051-3059.
10.1007/s00213-016-4348-0.
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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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