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-Åsberg 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.

• Klíčová slova
• LC-MS/MS, biomarker in depression, immune response, major depressive disorder, plasma proteomics, symptom presentation, treatment response,
• Publikační typ
• časopisecké články MeSH

AIMS: Statins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta-analysis of controlled trials. METHODS: A systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed- or random-effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD -0.48, 95% CI -0.87, -0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy. CONCLUSIONS: The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.

• Klíčová slova
• adipose tissue, cytokine, ezetimibe, pleiotropic, statin, tumour necrosis factor α,
• MeSH
• adiponektin krev   MeSH
• anticholesteremika farmakologie   terapeutické užití   MeSH
• ateroskleróza krev   farmakoterapie   MeSH
• ezetimib farmakologie   terapeutické užití   MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• interleukin-6 krev   MeSH
• kombinovaná farmakoterapie metody   MeSH
• leptin krev   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• statiny farmakologie   terapeutické užití   MeSH
• TNF-alfa krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• srovnávací studie MeSH
• systematický přehled MeSH
• Názvy látek
• adiponektin MeSH
• ADIPOQ protein, human MeSH Prohlížeč
• anticholesteremika MeSH
• ezetimib MeSH
• IL6 protein, human MeSH Prohlížeč
• inhibitor aktivátoru plazminogenu 1 MeSH
• interleukin-6 MeSH
• leptin MeSH
• SERPINE1 protein, human MeSH Prohlížeč
• statiny MeSH
• TNF-alfa MeSH