Křenek Pavel, Bartečková Eliška, Makarová Markéta, Pompa Tomáš, Fialová Kučerová Jana, Kučera Jan, Damborská Alena, Hořínková Jana, Bienertová-Vašků Julie
Department of Psychiatry, Faculty of Medicine, Masaryk University and University Hospital Brno, Brno, Czechia.
Department of Physical Activities and Health Sciences, Faculty of Sport Science, Masaryk University, Brno, Czechia.
Front Psychiatry. 2024 Sep 17;15:1425552. doi: 10.3389/fpsyt.2024.1425552. eCollection 2024.
This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode.
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).
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.
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.
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.
本研究旨在探讨急性发作期重度抑郁症（MDD）患者血浆蛋白质组与临床特征之间的关系。
在这项纵向观察性研究中，对26名因中度至重度MDD住院的患者进行了分析。该研究采用液相色谱串联质谱法（LC-MS/MS）以及临床指标，包括源自蒙哥马利-Åsberg抑郁评定量表（MADRS）的症状学。在急性抑郁发作时和治疗6周时进行血浆蛋白分析。分析方法包括微阵列数据线性模型（LIMMA）、加权相关网络分析（WGCNA）、广义线性模型、随机森林以及注释、可视化与整合发现数据库（DAVID）。
识别出五个不同的血浆蛋白模块，它们与特定的生物学过程相关，并与症状表现、疾病轨迹和治疗反应独特相关。一个富含与适应性免疫相关蛋白质的模块与躯体综合征的表现、治疗反应相关，且与实现缓解呈负相关。一个与细胞黏附相关的模块与情感症状和意志缺失有关，并在首发发作和治疗反应中起作用。另一个以参与血液凝固和脂质转运的蛋白质为特征的模块与多种MDD症状呈负相关，且主要与精神病性症状的表现相关。
本研究指出血浆蛋白质组与MDD临床表现之间存在复杂的相互作用，表明躯体、情感和精神病性症状可能代表MDD不同的内表型表现。这些见解为推进靶向治疗策略和诊断工具具有潜在意义。
该研究样本量有限且采用自然主义设计，涵盖多种治疗方式，存在方法学上的限制。此外，分析集中在外周血蛋白质上，可能对可解释性有影响。
