Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity

Harrison, Neil A., Brydon, Lena, Walker, Cicely, Gray, Marcus A., Steptoe, Andrew and Critchley, Hugo D. (2009) Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biological Psychiatry, 66 5: 407-414. doi:10.1016/j.biopsych.2009.03.015

Author Harrison, Neil A.
Brydon, Lena
Walker, Cicely
Gray, Marcus A.
Steptoe, Andrew
Critchley, Hugo D.
Title Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
Publication date 2009-09
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2009.03.015
Volume 66
Issue 5
Start page 407
End page 414
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Formatted abstract
Background: Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-α induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines.
Objectives: To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing.
Methods: In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Mood questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed an implicit emotional face perception task during functional magnetic resonance imaging. Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression.
Results: Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at 3 hours. Inflammation-associated mood deterioration correlated with enhanced activity within subgenual anterior cingulate cortex (sACC) (a region implicated in the etiology of depression) during emotional face processing. Furthermore, inflammation-associated mood change reduced connectivity of sACC to amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus, which was modulated by peripheral interleukin-6.
Conclusions: Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokines modulate this mood-dependent sACC connectivity, suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression.
Keyword Cytokines
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Advanced Imaging Publications
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Created: Tue, 23 Oct 2012, 16:51:01 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging