Dissection of the clinical phenome of major depressive disorder into subdomains and subgroups in relation to activated immune-inflammatory profiles

作者：Mengqi Niu, Yingqian Zhang, Xu Zhang, Chenkai Yangyang, Xiaoman Zhuang, Jing Li, Michael Maes · 发表于：medRxiv · 年份：2025 · DOI：10.1101/2025.10.21.25338439 · 被引用次数：9 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol

Abstract Background Major depressive disorder (MDD) is a prevalent mood disorder characterized by low remission rates and a high risk of suicide. It encompasses various clinical domains, including depression, anxiety, vegetative, physiosomatic and melancholic symptoms, and suicidal behaviors. Aims To dissect the clinical phenome of MDD, identify potential constructs within the symptom domains, delineate MDD subclasses, investigate the predictive role of recurrence of illness (ROI) on the phenome, and analyze the relationship between those clinical features and immune activation biomarkers. Methods A total of 125 MDD patients and 40 healthy controls were recruited for this study. Assays included serum immunological features (M1, Th1, Th2, Th17, IRS, CIRS, and TNF signaling), negative acute phase proteins (APPs; transferrin, albumin), sCD40L, EGF, and Flt-3L. Results Bifactor analysis integrated multiple clinical domains into a general factor, labeled “OSOD” (overall severity of depression), while extracting a single group factor of physiosomatic symptoms. Cluster analysis identified two subgroups of MDD: major dysmood disorder (MDMD) and simple dysmood disorder (SDMD). ROI mediates the impact of adverse childhood experiences on OSOD and correlates with enhanced immune activation (increased Th17). Downregulation of negative APPs and Flt-3L alongside increased EGF and TNF signaling distinguish MDMD versus SDMD or MDD from controls with great accuracy. Up to 60% of MDD patients s...