Dataset Information

Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience.

ABSTRACT: The intuitive association between self-focused rumination in major depressive disorder (MDD) and the self-referential operations performed by the brain's default-mode network (DMN) has prompted interest in examining the role of the DMN in MDD. In this article, we present meta-analytic findings showing reliably increased functional connectivity between the DMN and subgenual prefrontal cortex (sgPFC)-connectivity that often predicts levels of depressive rumination. We also present meta-analytic findings that, while there is reliably increased regional cerebral blood flow in sgPFC in MDD, no such abnormality has been reliably observed in nodes of the DMN. We then detail a model that integrates the body of research presented. In this model, we propose that increased functional connectivity between sgPFC and the DMN in MDD represents an integration of the self-referential processes supported by the DMN with the affectively laden, behavioral withdrawal processes associated with sgPFC-an integration that produces a functional neural ensemble well suited for depressive rumination and that, in MDD, abnormally taxes only sgPFC and not the DMN. This synthesis explains a broad array of existing data concerning the neural substrates of depressive rumination and provides an explicit account of functional abnormalities in sgPFC in MDD.

SUBMITTER: Hamilton JP

PROVIDER: S-EPMC4524294 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience.

Hamilton J Paul JP Farmer Madison M Fogelman Phoebe P Gotlib Ian H IH

Biological psychiatry 20150224 4

The intuitive association between self-focused rumination in major depressive disorder (MDD) and the self-referential operations performed by the brain's default-mode network (DMN) has prompted interest in examining the role of the DMN in MDD. In this article, we present meta-analytic findings showing reliably increased functional connectivity between the DMN and subgenual prefrontal cortex (sgPFC)-connectivity that often predicts levels of depressive rumination. We also present meta-analytic fi ...[more]

PMID: 25861700

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Project description: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.

Dataset Information

Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience.

Publications

Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience.

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