ReviewDepressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience
Section snippets
Properties of the DMN
In working to elucidate the role of the DMN in supporting ruminative processes in MDD, it is important to understand the nature of the operations carried out within the ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), two regions implicated most reliably in this network. Investigators have documented activation in vmPFC during valuation of goal-directed choices (13), while individuals are forming preference judgments (14), and as people are determining the financial
Resting-State Functional Magnetic Resonance Imaging
There are now a number of studies that have examined resting-state functional magnetic resonance imaging (fMRI) connectivity of the DMN in MDD. To identify the most robust findings in this literature, we conducted for this review a systematic meta-analysis of these studies. Briefly, we searched the Web of Science for articles with titles or topics matching the search phrase [depress* AND (fMRI OR “functional MRI” OR “functional magnetic”) AND default]. Among the articles that met these search
The Function of sgPFC
Most work examining the functioning of sgPFC has been conducted in the context of clinical depression and sad mood. Specifically, researchers frequently report elevated sgPFC activity associated with a state of depression (42, 43, 44) or with response to negative affective challenge in MDD (46) or, in nondepressed persons, with sad mood induced either through elaboration of sad autobiographical scripts (43) or through inflammation challenge (53). Although these are important findings, they beg
Limitations
It is important to acknowledge that while the current synthesis presents a plausible and integrative neural account of depressive rumination, it would benefit from elaboration in two ways. First, our model does not specify a mechanism underlying increased functional connectivity between sgPFC and the DMN in MDD. In this context, given findings that gamma-aminobutyric acid (GABA) deficits are prevalent in MDD (63) and that GABA concentrations in pericingulate cortex may control fluctuations of
Summary and Future Directions
In this review, we discussed findings suggesting that increased functional connectivity between sgPFC and the DMN in MDD is a neural substrate of depressive rumination. We demonstrated how this neural conceptualization of rumination in MDD can account both for the involvement of the DMN in ruminative responding in depression and for the lack of DMN rCBF abnormalities documented in MDD. We also described how our neural model of ruminative responding in MDD provides an explicit and intuitive
Acknowledgments and Disclosures
Preparation of this article was facilitated by National Institute of Mental Health Grant MH74849 to Ian Gotlib.
We thank Marc Berman for performing additional analyses on his functional neuroimaging data and sharing his findings with us. We thank Wayne Drevets for his insightful comments on an earlier version of this manuscript. We dedicate this article to the memory of Susan Nolen-Hoeksema and her pioneering work on rumination in depression.
Dr. Hamilton, Ms. Farmer, Ms. Fogelman, and Dr. Gotlib
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