Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Neuroimage Clin. 2021;30:102570. doi: 10.1016/j.nicl.2021.102570. Epub 2021 Jan 18.
Resting-state functional connectivity changes in the default mode network (DMN) of patients with major depressive disorder (MDD) have been linked to rumination. The DMN is divided into three subsystems: a midline Core, a dorsal medial prefrontal cortex (DMPFC) subsystem, and a medial temporal lobe (MTL) subsystem. We examined resting-state functional connectivity within and between DMN subsystems in MDD and its association with rumination. First, we conducted a meta-analysis on a large multi-site dataset of 618 MDD and 683 controls to quantify the differences in DMN subsystem functional connectivity between MDD and controls. Second, we tested the association of DMN subsystem functional connectivity and rumination in a sample of 115 unmedicated participants with symptoms of anxiety/depression and 48 controls. In our meta-analysis, only functional connectivity in the DMN Core was significantly reduced in MDD compared to controls (g = -0.246, CI = [-0.417; -0.074], pFDR = 0.048). Functional connectivity in the DMPFC subsystem and between the Core and DMPFC subsystems was slightly reduced but not significantly (g = -0.162, CI = [-0.310; -0.013], pFDR = 0.096; g = -0.249, CI = [-0.464; -0.034], pFDR = 0.084). Results were heterogeneous across sites for connectivity in the Core and between Core and DMPFC (I = 0.348 and I = 0.576 respectively). Prediction intervals consistently encompassed 0. In the independent sample we collected, functional connectivity within the DMN Core, DMPFC and between Core and DMPFC was not reduced in MDD compared to controls (all pFDR > 0.05). Trait rumination did not predict connectivity within and between DMN subsystems (all pFDR > 0.05). We conclude that MDD as a diagnostic category shows slightly reduced functional connectivity within the DMN Core, independent of illness duration, treatment, symptoms and trait rumination. However, this effect is small, highly variable and heterogeneous across samples, so that we could only detect it at the meta-analytic level, with a sample size of several hundreds. Our results indicate that reduced Core DMN connectivity has significant limitations as a potential clinical or prognostic marker for the diagnosis of MDD and might be more relevant to consider as a characteristic distinguishing a subgroup of individuals within this diagnostic category.
静息态功能连接变化在默认模式网络（DMN）的患者与重度抑郁症（MDD）已经与反刍。DMN 分为三个子系统：中线核心，背内侧前额叶皮质（DMPFC）子系统和内侧颞叶（MTL）子系统。我们研究了静息状态功能连接在 DMN 子系统内和子系统之间在 MDD 及其与反刍的关系。首先，我们进行了一项荟萃分析，对 618 例 MDD 和 683 例对照的大型多地点数据集进行了分析，以量化 MDD 与对照组之间 DMN 子系统功能连接的差异。其次，我们在 115 名未经治疗的有焦虑/抑郁症状的参与者和 48 名对照者的样本中测试了 DMN 子系统功能连接与反刍的关系。在我们的荟萃分析中，只有 DMN 核心的功能连接在 MDD 中与对照组相比明显降低（g=-0.246，CI=[-0.417；-0.074]，pFDR=0.048）。DMPFC 子系统和核心与 DMPFC 子系统之间的功能连接略有降低，但无统计学意义（g=-0.162，CI=[-0.310；-0.013]，pFDR=0.096；g=-0.249，CI=[-0.464；-0.034]，pFDR=0.084）。对于核心和核心与 DMPFC 之间的连接，站点之间的结果存在异质性（I=0.348 和 I=0.576）。预测区间一致地包含 0。在我们收集的独立样本中，与对照组相比，DMN 核心、DMPFC 以及核心与 DMPFC 之间的功能连接在 MDD 中没有降低（所有 pFDR>0.05）。特质反刍并不能预测 DMN 子系统内和子系统之间的连接（所有 pFDR>0.05）。我们得出结论，作为一个诊断类别，MDD 显示出在 DMN 核心内的功能连接略有降低，与疾病持续时间、治疗、症状和特质反刍无关。然而，这种效应很小，高度可变，在样本之间存在异质性，因此我们只能在荟萃分析水平上检测到它，样本量为几百个。我们的结果表明，核心 DMN 连接的减少作为 MDD 诊断的潜在临床或预后标志物具有显著的局限性，并且可能更相关的是将其作为区分该诊断类别中个体亚组的特征来考虑。
