The default mode network and self-referential processes in depression
- Yvette I. Shelinea,b,c,1,
- Deanna M. Barcha,b,d,
- Joseph L. Pricee,
- Melissa M. Rundleb,
- S. Neil Vaishnavib,
- Abraham Z. Snyderb,c,
- Mark A. Mintuna,b,
- Suzhi Wanga,
- Rebecca S. Coalsonb,c,2 and
- Marcus E. Raichleb,c,2
- Departments of aPsychiatry
- bRadiology
- cNeurology
- dPsychology
- eAnatomy and NeurobiologyWashington UniversitySt. LouisMO 63110
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Contributed by Marcus E. RaichleDecember 12, 2008 (received for review August 26, 2008)
Abstract
The recently discovered default mode network (DMN) is a group of areas in the human brain characterized, collectively, by functions of a self-referential nature. In normal individuals, activity in the DMN is reduced during nonself-referential goal-directed tasks, in keeping with the folk-psychological notion of losing one's self in one's work. Imaging and anatomical studies in major depression have found alterations in both the structure and function in some regions that belong to the DMN, thus, suggesting a basis for the disordered self-referential thought of depression. Here, we sought to examine DMN functionality as a network in patients with major depression, asking whether the ability to regulate its activity and, hence, its role in self-referential processing, was impaired. To do so, we asked patients and controls to examine negative pictures passively and also to reappraise them actively. In widely distributed elements of the DMN [ventromedial prefrontal cortex prefrontal cortex (BA 10), anterior cingulate (BA 24/32), lateral parietal cortex (BA 39), and lateral temporal cortex (BA 21)], depressed, but not control subjects, exhibited a failure to reduce activity while both looking at negative pictures and reappraising them. Furthermore, looking at negative pictures elicited a significantly greater increase in activity in other DMN regions (amygdala, parahippocampus, and hippocampus) in depressed than in control subjects. These data suggest depression is characterized by both stimulus-induced heightened activity and a failure to normally down-regulate activity broadly within the DMN. These findings provide a brain network framework within which to consider the pathophysiology of depression.
Footnotes
- 1To whom correspondence may be addressed at: Washington University School of Medicine, Department of Psychiatry, 660 South Euclid Avenue St. Louis, MO 63110. E-mail: yvette{at}npg.wustl.edu
- 2To whom correspondence may be addressed. E-mail: marc{at}npg.wustl.edu
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Author contributions: Y.I.S., D.M.B., and M.A.M. designed research; Y.I.S., M.M.R., and S.W. performed research; S.N.V. contributed new reagents/analytic tools; Y.I.S., D.M.B., J.L.P., M.M.R., S.N.V., A.Z.S., S.W., and R.S.C. analyzed data; and Y.I.S., D.M.B., J.L.P., and M.E.R. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0812686106/DCSupplemental.
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Freely available online through the PNAS open access option.
- © 2009 by The National Academy of Sciences of the USA




