Hannon Kayla, Easley Ty, Zhang Wei, Lew Daphne, Sotiras Aristeidis, Sheline Yvette I, Marquand Andre, Barch Deanna M, Bijsterbosch Janine D
Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri.
Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri.
Biol Psychiatry. 2025 Oct 1;98(7):558-567. doi: 10.1016/j.biopsych.2025.04.025. Epub 2025 May 8.
Patients with depression vary from one another in their clinical and neuroimaging presentation, but the relationship between clinical and neuroimaging sources of variation is poorly understood. Determining sources of heterogeneity in depression is important to gain insights into its diverse and complex neural etiology. In this study, we aimed to test whether depression heterogeneity is characterized by subgroups that differ both clinically and neurobiologically and/or whether multiple neuroimaging profiles give rise to the same clinical presentation.
This study utilized population-based data from the UK Biobank over multiple imaging sites. Clinically dissociated groups were selected to isolate clinical characteristics of depression (symptoms of anhedonia, depressed mood, and somatic disturbance; severity indices of lifetime chronicity and acute impairment; and late onset). Residual neuroimaging heterogeneity within each group was assessed using neuroimaging-driven clustering.
The clinically dissociated subgroups had significantly larger neuroimaging normative deviations than a comparison heterogeneous group and had distinct neuroimaging profiles from each other. Imaging-driven clustering within each clinically dissociated group identified 2 stable subtypes within the acute impairment group that differed significantly in cognitive ability despite identical clinical profiles.
The study identified distinct neuroimaging profiles related to particular clinical depression features that may explain inconsistencies in the literature and subclusters within the acute impairment group with cognitive differences that were only differentiable by neuroimaging. Our results provide evidence that multiple neuroimaging profiles may give rise to the same clinical presentation, emphasizing the presence of complex interactions between clinical and neuroimaging sources of heterogeneity.
抑郁症患者在临床和神经影像学表现上各不相同，但临床和神经影像学变异来源之间的关系却知之甚少。确定抑郁症异质性的来源对于深入了解其多样且复杂的神经病因至关重要。在本研究中，我们旨在测试抑郁症的异质性是否以临床和神经生物学上均存在差异的亚组为特征，以及/或者多种神经影像学特征是否会导致相同的临床表现。
本研究利用了来自英国生物银行多个成像站点的基于人群的数据。选择临床解离组以分离抑郁症的临床特征（快感缺失、情绪低落和躯体障碍症状；终生慢性和急性损伤的严重程度指数；以及晚发性）。使用神经影像学驱动的聚类评估每组内残留的神经影像学异质性。
与一个比较异质性组相比，临床解离亚组的神经影像学规范偏差显著更大，且彼此具有不同的神经影像学特征。每个临床解离组内的成像驱动聚类在急性损伤组中识别出2个稳定亚型，尽管临床特征相同，但认知能力存在显著差异。
该研究确定了与特定临床抑郁症特征相关的不同神经影像学特征，这可能解释了文献中的不一致性，以及急性损伤组内具有认知差异的亚群，这些差异只能通过神经影像学来区分。我们的结果提供了证据，表明多种神经影像学特征可能导致相同的临床表现，强调了临床和神经影像学异质性来源之间存在复杂的相互作用。
