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Molecular serum signature of treatment resistant depression
Tillmann Ruland1,2, Man K Chan3, Pawel Stocki3
1Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany. Tillmann.Ruland@ukmuenster.de.
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.
Insights
This study identified immune and complement activation proteins as potential biomarkers for treatment-resistant depression (TRD). These findings may help clinicians identify high-risk patients, though results require cautious interpretation due to subtle molecular changes.
Area of Science:
- Neuroscience
- Biochemistry
- Clinical Medicine
Background:
- Major depressive disorder (MDD) often leads to treatment resistance, with limited understanding of underlying molecular mechanisms.
- Current research on treatment-resistant depression (TRD) has focused on a narrow range of molecules and genes, highlighting a need for novel biomarkers.
Purpose of the Study:
- To identify peripheral biomarkers for TRD using advanced high-throughput proteomic platforms.
- To evaluate TRD biomarkers based on the Thase and Rush staging model (TRM) and the Maudsley Staging Model (MSM).
Main Methods:
- Serum samples from 65 MDD inpatients were analyzed using label-free liquid chromatography mass spectrometry (LC-MS(E)) and selective reaction monitoring (SRM).
- A multiplex bead-based assay was also employed to analyze protein levels.
Main Results:
- LC-MS(E) revealed significant differences in proteins related to acute phase response, complement activation, and coagulation between staging groups.
- Multiplex assay indicated TNF-α levels differed significantly in the TRM comparison (p=0.045).
- SRM analysis associated changes in apolipoproteins A-I, M, and F with TRM, but not MSM.
Conclusions:
- Proteins involved in immune and complement activation pathways show potential as peripheral biomarkers for identifying high-risk TRD patients.
- The subtle nature of observed molecular changes necessitates cautious interpretation of these findings.
