Molecular serum signature of treatment resistant depression

• Published in: Psychopharmacology 2016-08, Vol.233 (15-16), p.3051-3059
• Main Authors: Ruland, Tillmann, Chan, Man K., Stocki, Pawel, Grosse, Laura, Rothermundt, Matthias, Cooper, Jason D., Arolt, Volker, Bahn, Sabine
• Format: Article
• Language: English
• Subjects: Adult; Antidepressive Agents - therapeutic use; Biological markers; Biomarkers; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Blood Coagulation; Care and treatment; Chromatography, Liquid; Cohort Studies; Complement Activation; Cytokines - blood; Depressive Disorder, Major - blood; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Depressive Disorder, Treatment-Resistant - blood; Depressive Disorder, Treatment-Resistant - drug therapy; Depressive Disorder, Treatment-Resistant - metabolism; DNA Mismatch Repair; Female; Humans; Logistic Models; Major depressive disorder; Male; Mass Spectrometry; Mental depression; Middle Aged; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Proteomics; Psychiatry; Psychopharmacology; Severity of Illness Index; Tumor Necrosis Factor-alpha - blood
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-016-4348-0

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-MS E ) and selective reaction monitoring (SRM), as well as a multiplex bead based assay. Results In the LC-MS E 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.