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 (I² = 0.348 and I² = 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.

重度抑郁症（MDD）患者默认模式网络（DMN）静息态功能连接的变化与沉思有关。DMN 分为三个子系统：中线核心、背侧内侧前额叶皮层 (DMPFC) 子系统和内侧颞叶 (MTL) 子系统。我们检查了 MDD 中 DMN 子系统内部和之间的静息态功能连接及其与沉思的关联。首先，我们对 618 个 MDD 和 683 个对照的大型多站点数据集进行了荟萃分析，以量化 MDD 和对照之间 DMN 子系统功能连接的差异。其次，我们在 115 名具有焦虑/抑郁症状的未用药参与者和 48 名对照样本中测试了 DMN 子系统功能连接和沉思的关联。

在我们的荟萃分析中，与对照组相比，MDD 中只有 DMN 核心中的功能连接显着降低（g = -0.246，CI = [-0.417；-0.074]，pFDR = 0.048）。DMPFC 子系统以及核心和 DMPFC 子系统之间的功能连接略有减少，但并不显着（g = -0.162，CI = [-0.310；-0.013]，pFDR = 0.096；g = -0.249，CI = [-0.464； −0.034]，pFDR = 0.084）。核心内以及核心与 DMPFC 之间的连接性在各个站点之间存在异质性（分别为 I ²  = 0.348 和 I ²  = 0.576）。预测区间始终包含 0。在我们收集的独立样本中，与对照组相比，MDN 核心、DMPFC 内以及核心和 DMPFC 之间的功能连接在 MDD 中并未降低（所有 pFDR > 0.05）。特质反思并不能预测 DMN 子系统内部和之间的连接性（所有 pFDR > 0.05）。

我们得出的结论是，MDD 作为一种诊断类别，显示 DMN 核心内的功能连接略有减少，与病程、治疗、症状和特质思考无关。然而，这种效应很小，样本间差异很大且异质，因此我们只能在样本量为数百的荟萃分析水平上检测到它。我们的结果表明，核心 DMN 连接性的降低作为 MDD 诊断的潜在临床或预后标志物具有显着的局限性，并且可能更适合考虑作为区分该诊断类别中的个体亚组的特征。