Correlating Plasma Protein Profiles with Symptomatology and Treatment Response in Acute Phase and Early Remission of Major Depressive Disorder

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 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.Conclusions: 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.研究目的：本研究旨在探讨急性发作期治疗期间，血浆蛋白质组与重度抑郁症（Major Depressive Disorder, MDD）的临床特征之间的关联。 研究方法：本项纵向观察性研究共纳入26例因中重度抑郁症住院的患者进行分析。本研究采用液相色谱-串联质谱（Liquid Chromatography with Tandem Mass Spectrometry, LC-MS/MS）结合临床指标开展分析，临床指标包括基于蒙哥马利-阿斯伯格抑郁量表（Montgomery-Åsberg Depression Rating Scale, MADRS）评估的症状学数据。分别在急性抑郁发作初期及治疗6周后采集血浆样本进行蛋白质组分析。分析方法涵盖微阵列数据线性模型（Linear Models for Microarray Data, LIMMA）、加权基因共表达网络分析（Weighted Correlation Network Analysis, WGCNA）、广义线性模型、随机森林，以及注释、可视化和整合发现数据库（The Database for Annotation, Visualization and Integrated Discovery, DAVID）。 研究结果：本研究共鉴定出5个独特的血浆蛋白质共表达模块，这些模块与特定生物学过程相关，并分别与症状表现、疾病病程及治疗应答存在特异性关联。其中一个富含适应性免疫相关蛋白的模块与躯体综合征的发生、治疗应答相关，且与症状缓解的实现呈负相关。另一个与细胞黏附相关的模块与情感症状及意志缺乏相关，且在初始发作及治疗应答中发挥作用。另有一个以凝血及脂质转运相关蛋白为特征的模块与多种重度抑郁症症状呈负相关，且主要与精神病性症状的出现相关。 研究结论：本研究揭示了血浆蛋白质组与重度抑郁症临床表型之间存在复杂的相互作用，提示躯体、情感及精神病性症状可能分别代表重度抑郁症不同的内表型表现形式。上述研究结果有望为开发针对性治疗策略及诊断工具提供理论依据。 研究局限性：本研究样本量有限，且采用自然主义研究设计，涵盖了多种治疗方式，因此存在方法学局限。此外，本分析仅聚焦于外周血蛋白质，这可能对结果的解读产生一定影响。