QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 15, 2007, 27(33):8877-8884; doi:10.1523/JNEUROSCI.2063-07.2007

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Johnstone, T. Articles by Davidson, R. J. Search for Related Content PubMed PubMed Citation Articles by Johnstone, T. Articles by Davidson, R. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB OXYGEN

 Previous Article  |  Next Article 

Neurobiology of Disease
Failure to Regulate: Counterproductive Recruitment of Top-Down Prefrontal-Subcortical Circuitry in Major Depression

Tom Johnstone,¹ Carien M. van Reekum,² Heather L. Urry,^1,4 Ned H. Kalin,^2,3 and Richard J. Davidson^1,2,3

¹Waisman Laboratory for Brain Imaging and Behavior, ²Department of Psychology, and ³Department of Psychiatry, University of Wisconsin–Madison, Madison, Wisconsin 53705, and ⁴Department of Psychology, Tufts University, Medford, Massachusetts 02155

Correspondence should be addressed to Tom Johnstone, Waisman Laboratory for Brain Imaging and Behavior, 1500 Highland Avenue, Madison, WI 53705. Email: itjohnstone{at}wisc.edu

Although depressed mood is a normal occurrence in response to adversity in all individuals, what distinguishes those who are vulnerable to major depressive disorder (MDD) is their inability to effectively regulate negative mood when it arises. Investigating the neural underpinnings of adaptive emotion regulation and the extent to which such processes are compromised in MDD may be helpful in understanding the pathophysiology of depression. We report results from a functional magnetic resonance imaging study demonstrating left-lateralized activation in the prefrontal cortex (PFC) when downregulating negative affect in nondepressed individuals, whereas depressed individuals showed bilateral PFC activation. Furthermore, during an effortful affective reappraisal task, nondepressed individuals showed an inverse relationship between activation in left ventrolateral PFC and the amygdala that is mediated by the ventromedial PFC (VMPFC). No such relationship was found for depressed individuals, who instead show a positive association between VMPFC and amygdala. Pupil dilation data suggest that those depressed patients who expend more effort to reappraise negative stimuli are characterized by accentuated activation in the amygdala, insula, and thalamus, whereas nondepressed individuals exhibit the opposite pattern. These findings indicate that a key feature underlying the pathophysiology of major depression is the counterproductive engagement of right prefrontal cortex and the lack of engagement of left lateral-ventromedial prefrontal circuitry important for the downregulation of amygdala responses to negative stimuli.

Key words: depression; prefrontal cortex; amygdala; emotion; regulation; fMRI

---

Received May 5, 2007; revised June 16, 2007; accepted July 5, 2007.

Correspondence should be addressed to Tom Johnstone, Waisman Laboratory for Brain Imaging and Behavior, 1500 Highland Avenue, Madison, WI 53705. Email: itjohnstone{at}wisc.edu

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2007 27: i. [Full Text]  

This article has been cited by other articles:

				A. Hermann, A. Schafer, B. Walter, R. Stark, D. Vaitl, and A. Schienle Emotion regulation in spider phobia: role of the medial prefrontal cortex Soc Cogn Affect Neurosci, April 27, 2009; (2009) nsp013v1. [Abstract] [Full Text] [PDF]

				P. M. Fisher, C. C. Meltzer, J. C. Price, R. L. Coleman, S. K. Ziolko, C. Becker, E. L. Moses-Kolko, S. L. Berga, and A. R. Hariri Medial Prefrontal Cortex 5-HT2A Density Is Correlated with Amygdala Reactivity, Response Habituation, and Functional Coupling Cereb Cortex, March 25, 2009; (2009) bhp022v1. [Abstract] [Full Text] [PDF]

				C. Lemogne, G. le Bastard, H. Mayberg, E. Volle, L. Bergouignan, S. Lehericy, J.-F. Allilaire, and P. Fossati In search of the depressive self: extended medial prefrontal network during self-referential processing in major depression Soc Cogn Affect Neurosci, March 23, 2009; (2009) nsp008v1. [Abstract] [Full Text] [PDF]

				M. Desseilles, E. Balteau, V. Sterpenich, T. T. Dang-Vu, A. Darsaud, G. Vandewalle, G. Albouy, E. Salmon, F. Peters, C. Schmidt, et al. Abnormal Neural Filtering of Irrelevant Visual Information in Depression J. Neurosci., February 4, 2009; 29(5): 1395 - 1403. [Abstract] [Full Text] [PDF]

				C. F. Geier, K. Garver, R. Terwilliger, and B. Luna Development of Working Memory Maintenance J Neurophysiol, January 1, 2009; 101(1): 84 - 99. [Abstract] [Full Text] [PDF]

				A. T. Beck The Evolution of the Cognitive Model of Depression and Its Neurobiological Correlates Am J Psychiatry, August 1, 2008; 165(8): 969 - 977. [Abstract] [Full Text] [PDF]

				S. Whittle, M. B. H. Yap, M. Yucel, A. Fornito, J. G. Simmons, A. Barrett, L. Sheeber, and N. B. Allen Prefrontal and amygdala volumes are related to adolescents' affective behaviors during parent-adolescent interactions PNAS, March 4, 2008; 105(9): 3652 - 3657. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help