Yu Meichen, Cullen Nicholas, Linn Kristin A, Oathes Desmond J, Seok Darsol, Cook Philip A, Duprat Romain, Aselcioglu Irem, Moore Tyler M, Davatzikos Christos, Oquendo Maria A, Weissman Myrna M, Shinohara Russell T, Sheline Yvette I
Center for Neuromodulation in Depression and Stress, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mol Psychiatry. 2021 Jul;26(7):2764-2775. doi: 10.1038/s41380-021-01039-8. Epub 2021 Feb 15.
Abnormalities in brain structural measures, such as cortical thickness and subcortical volumes, are observed in patients with major depressive disorder (MDD) who also often show heterogeneous clinical features. This study seeks to identify the multivariate associations between structural phenotypes and specific clinical symptoms, a novel area of investigation. T1-weighted magnetic resonance imaging measures were obtained using 3 T scanners for 178 unmedicated depressed patients at four academic medical centres. Cortical thickness and subcortical volumes were determined for the depressed patients and patients' clinical presentation was characterized by 213 item-level clinical measures, which were grouped into several large, homogeneous categories by K-means clustering. The multivariate correlations between structural and cluster-level clinical-feature measures were examined using canonical correlation analysis (CCA) and confirmed with both 5-fold and leave-one-site-out cross-validation. Four broad types of clinical measures were detected based on clustering: an anxious misery composite (composed of item-level depression, anxiety, anhedonia, neuroticism and suicidality scores); positive personality traits (extraversion, openness, agreeableness and conscientiousness); reported history of physical/emotional trauma; and a reported history of sexual abuse. Responses on the item-level anxious misery measures were negatively associated with cortical thickness/subcortical volumes in the limbic system and frontal lobe; reported childhood history of physical/emotional trauma and sexual abuse measures were negatively correlated with entorhinal thickness and left hippocampal volume, respectively. In contrast, the positive traits measures were positively associated with hippocampal and amygdala volumes and cortical thickness of the highly-connected precuneus and cingulate cortex. Our findings suggest that structural brain measures may reflect neurobiological mechanisms underlying MDD features.
在重度抑郁症（MDD）患者中观察到脑结构测量指标异常，如皮质厚度和皮质下体积，这些患者通常还表现出异质性临床特征。本研究旨在确定结构表型与特定临床症状之间的多变量关联，这是一个新的研究领域。在四个学术医疗中心，使用3T扫描仪对178名未接受药物治疗的抑郁症患者进行了T1加权磁共振成像测量。测定了抑郁症患者的皮质厚度和皮质下体积，并通过213项个体水平的临床测量对患者的临床表现进行了特征描述，这些测量通过K均值聚类被分为几个大的、同质的类别。使用典型相关分析（CCA）检查了结构与聚类水平临床特征测量之间的多变量相关性，并通过5折交叉验证和留一中心交叉验证进行了确认。基于聚类检测到四种广泛类型的临床测量：一种焦虑痛苦综合指标（由个体水平的抑郁、焦虑、快感缺失、神经质和自杀倾向得分组成）；积极的人格特质（外向性、开放性、宜人性和尽责性）；报告的身体/情感创伤史；以及报告的性虐待史。个体水平焦虑痛苦测量的反应与边缘系统和额叶的皮质厚度/皮质下体积呈负相关；报告的童年身体/情感创伤史和性虐待测量分别与内嗅皮质厚度和左侧海马体积呈负相关。相比之下，积极特质测量与海马体和杏仁核体积以及高度连接的楔前叶和扣带回皮质的皮质厚度呈正相关。我们的研究结果表明，脑结构测量可能反映了MDD特征背后的神经生物学机制。
