Molecular serum signature of treatment resistant depression.
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-MS(E)) and selective reaction monitoring (SRM), as well as a multiplex bead based assay.



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.



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.
Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany. Tillmann.Ruland@ukmuenster.de.|Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK. Tillmann.Ruland@ukmuenster.de.
Tillmann
T
Ruland
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
Man K
MK
Chan
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
Pawel
P
Stocki
Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.|Radiology Morphological Solutions, Rotterdam, The Netherlands.
Laura
L
Grosse
Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
Matthias
M
Rothermundt
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
Jason D
JD
Cooper
Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
Volker
V
Arolt
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
Sabine
S
Bahn
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003167:Complement Activation; D016207:Cytokines / Q000097:blood; D053843:DNA Mismatch Repair; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D061218:Depressive Disorder, Treatment-Resistant / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000928:Antidepressive Agents; D015415:Biomarkers; D016207:Cytokines; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
Mass spectrometry; Serum; Staging; Treatment resistant depression