Wang Xinyi, Wei Xinruo, Shao Junneng, Xue Li, Chen Zhilu, Yao Zhijian, Lu Qing
School of Psychology, Nanjing Normal University, Nanjing, China.
School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, China.
Hum Brain Mapp. 2025 Jun 1;46(8):e70215. doi: 10.1002/hbm.70215.
The heterogeneity of major depressive disorder (MDD) complicates the selection of effective treatments. While more studies have identified cluster-based MDD subtypes, they often overlook individual variability within subtypes. To address this, we applied latent dirichlet allocation to decompose resting-state functional connectivity (FC) into latent factors. It allows patients to express varying degrees of FC across multiple factors, retaining inter-individual variability. We enrolled 226 patients and 100 healthy controls to identify latent factors and examine their distinct patterns of hyper- and hypo-connectivity. We investigated the association between these connectivity patterns and treatment preferences. Additionally, we compared demographic characteristics, clinical symptoms, and longitudinal symptom improvements across the identified factors. We identified three factors. Factor 1, characterized by inter-network hyperconnectivity of the default mode network (DMN), was associated with treatment response to antidepressant monotherapy. Additionally, factor 1 was more frequently expressed by younger and highly educated patients, with significant improvements in cognitive symptoms. Conversely, factor 3, characterized by inter-networks and intra-networks hypoconnectivity of DMN, was associated with treatment response when combining antidepressants with stimulation therapy. Factor 2, characterized by global hypoconnectivity without DMN, was associated with higher baseline depression severity and anxiety symptoms. These three factors showed distinct treatment preferences and clinical characteristics. Importantly, our results suggested that patients with DMN hyperconnectivity benefited from monotherapy, while those with DMN hypoconnectivity benefited from combined treatments. Our approach allows for a unique composition of factors in each individual, potentially facilitating the development of more personalized treatment-related biomarkers.
重度抑郁症(MDD)的异质性使有效治疗方法的选择变得复杂。虽然越来越多的研究已经确定了基于聚类的MDD亚型,但它们往往忽略了亚型内的个体差异。为了解决这个问题,我们应用潜在狄利克雷分配将静息态功能连接(FC)分解为潜在因素。它允许患者在多个因素上表现出不同程度的FC,保留个体间的变异性。我们招募了226名患者和100名健康对照,以识别潜在因素并检查它们独特的高连接性和低连接性模式。我们研究了这些连接模式与治疗偏好之间的关联。此外,我们比较了已识别因素之间的人口统计学特征、临床症状和纵向症状改善情况。我们识别出三个因素。因素1的特征是默认模式网络(DMN)的网络间高连接性,与抗抑郁单药治疗的反应相关。此外,年轻和高学历患者更常表现出因素1,认知症状有显著改善。相反,因素3的特征是DMN的网络间和网络内低连接性,与抗抑郁药与刺激疗法联合使用时的治疗反应相关。因素2的特征是没有DMN的整体低连接性,与更高的基线抑郁严重程度和焦虑症状相关。这三个因素表现出不同的治疗偏好和临床特征。重要的是,我们的结果表明,DMN高连接性的患者从单药治疗中获益,而DMN低连接性的患者从联合治疗中获益。我们的方法允许每个个体有独特的因素组合,可能有助于开发更个性化的治疗相关生物标志物。