Institute for Brain Research and Rehabilitation, South China Normal University, 510631 Guangzhou, China; School of Psychology, South China Normal University, Guangzhou, China.
Department of Radiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong 510405, China; Department of Radiology, Guangzhou First People's Hospital, Guangdong 510180, China.
J Affect Disord. 2022 May 15;305:159-172. doi: 10.1016/j.jad.2022.02.052. Epub 2022 Feb 24.
Despite accumulating evidence for the hippocampus as a key dysfunctional node in major depressive disorder (MDD), previous findings are controversial possibly due to heterogeneous and small clinical samples, complicated hippocampal structure, and different imaging modalities and analytical methods.
We collected structural and resting-state functional MRI data from 100 first-episode, drug-naïve MDD patients and 99 healthy controls. A subset of the participants (34 patients and 33 controls) also completed a battery of neuropsychological tests and childhood trauma questionnaires. Seed-based morphological and functional (static and dynamic) connectivity were calculated for ten hippocampal subregions, followed by analyses of dynamic functional connectivity states (k-means clustering), connectivity cross-modality relationships (cosine similarity), and connectivity associations with clinical and neuropsychological variables (Spearman correlation).
Between-group comparisons revealed abnormal hippocampal connectivity in the patients that depended on 1) hippocampal subdivisions: the cornu ammonis (CA) was the most seriously affected subregion, in particular the right CA1 for functional connectivity alterations; 2) imaging modality: morphological connectivity revealed seldom and sporadic alterations with different lobes, while functional connectivity identified numerous and convergent alterations with prefrontal regions; and 3) time scale: dynamic functional connectivity was more sensitive than static functional connectivity, in particular in revealing alterations between the right CA1 and contralateral prefrontal cortex. Among the 34 patients, functional connectivity alterations of the CA1 were related to the history of childhood trauma in the patients.
Only a subset of the patients completed the neuropsychological tests, which may cause underestimation of cognitive relevance of hippocampal connectivity alterations.
Disrupted hippocampal CA1 functional connectivity plays key roles in the pathophysiology of MDD and may act as a potential diagnostic biomarker for the disease.
尽管越来越多的证据表明海马体是重度抑郁症（MDD）的关键功能障碍节点，但由于临床样本的异质性和小样本量、复杂的海马体结构以及不同的成像方式和分析方法，先前的研究结果存在争议。
我们从 100 名首发、未经药物治疗的 MDD 患者和 99 名健康对照者中收集了结构和静息状态功能 MRI 数据。部分参与者（34 名患者和 33 名对照者）还完成了一系列神经心理学测试和童年创伤问卷。我们计算了十个海马亚区的基于种子的形态学和功能（静态和动态）连接，然后分析了动态功能连接状态（k-均值聚类）、连接跨模态关系（余弦相似性）以及连接与临床和神经心理学变量的相关性（Spearman 相关性）。
组间比较显示，患者存在异常的海马连接，这种异常取决于 1）海马亚区：齿状回（CA）是受影响最严重的亚区，特别是右侧 CA1 的功能连接改变；2）成像方式：形态连接变化少见且分散于不同的脑叶，而功能连接则确定了与前额叶区域大量且趋同的变化；3）时间尺度：动态功能连接比静态功能连接更敏感，特别是在揭示右侧 CA1 和对侧前额叶皮质之间的变化时。在 34 名患者中，CA1 的功能连接变化与患者的童年创伤史有关。
只有一部分患者完成了神经心理学测试，这可能导致低估了海马连接改变的认知相关性。
受损的海马 CA1 功能连接在 MDD 的病理生理学中起关键作用，可能作为该疾病的潜在诊断生物标志物。
