Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression

Johnstone, T., Van Reekum, C. M. ORCID: https://orcid.org/0000-0002-1516-1101, Urry, H. L., Kalin, N. H. and Davidson, R. J. (2007) Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience, 27 (33). pp. 8877-8884. ISSN 0270-6474 doi: 10.1523/JNEUROSCI.2063-07.2007

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/4367
Identification Number/DOI	10.1523/JNEUROSCI.2063-07.2007
Refereed	Yes
Divisions	Interdisciplinary Research Centres (IDRCs) > Centre for Integrative Neuroscience and Neurodynamics (CINN) Life Sciences > School of Psychology and Clinical Language Sciences > Psychopathology and Affective Neuroscience No Reading authors. Back catalogue items
Uncontrolled Keywords	depression; prefrontal cortex; amygdala; emotion; regulation; fMRI
Publisher	Society for Neuroscience
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