Correlating plasma protein profiles with symptomatology and treatment response in acute phase and early remission of major depressive disorder

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Authors

KŘENEK Pavel BARTEČKOVÁ Eliška MAKAROVÁ Markéta POMPA Tomáš FIALOVÁ KUČEROVÁ Jana KUČERA Jan DAMBORSKÁ Alena HOŘÍNKOVÁ Jana DOBROVOLNÁ Julie

Year of publication 2024
Type Article in Periodical
Magazine / Source Frontiers in Psychiatry
MU Faculty or unit

Faculty of Medicine

Citation
web https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1425552/full
Doi http://dx.doi.org/10.3389/fpsyt.2024.1425552
Keywords major depressive disorder; plasma proteomics; LC-MS/MS; immune response; symptom presentation; treatment response; biomarker in depression
Description Objectives This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode.Methods In this longitudinal observational study, 26 patients hospitalized for moderate to severe MDD were analyzed. The study utilized Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) alongside clinical metrics, including symptomatology derived from the Montgomery-& Aring;sberg Depression Rating Scale (MADRS). Plasma protein analysis was conducted at the onset of acute depression and 6 weeks into treatment. Analytical methods comprised of Linear Models for Microarray Data (LIMMA), Weighted Correlation Network Analysis (WGCNA), Generalized Linear Models, Random Forests, and The Database for Annotation, Visualization and Integrated Discovery (DAVID).Results Five distinct plasma protein modules were identified, correlating with specific biological processes, and uniquely associated with symptom presentation, the disorder's trajectory, and treatment response. A module rich in proteins related to adaptive immunity was correlated with the manifestation of somatic syndrome, treatment response, and inversely associated with achieving remission. A module associated with cell adhesion was linked to affective symptoms and avolition, and played a role in the initial episodes and treatment response. Another module, characterized by proteins involved in blood coagulation and lipid transport, exhibited negative correlations with a variety of MDD symptoms and was predominantly associated with the manifestation of psychotic symptoms.Conclusion This research points to a complex interplay between the plasma proteome and MDD's clinical presentation, suggesting that somatic, affective, and psychotic symptoms may represent distinct endophenotypic manifestations of MDD. These insights hold potential for advancing targeted therapeutic strategies and diagnostic tools.Limitations The study's limited sample size and its naturalistic design, encompassing diverse treatment modalities, present methodological constraints. Furthermore, the analysis focused on peripheral blood proteins, with potential implications for interpretability.
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