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

Harrison, Neil A., Brydon, L., Walker, C., Gray, M.A., Steptoe, A. and Critchley, Hugo D. (2009) Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biological Psychiatry, 66 (5). pp. 407-414. ISSN 0006-3223

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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-alpha 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

Item Type: Article
Keywords: Cytokines, depression, fMRI, mood, peripheral inflammation, subgenual cingulate
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
?? RC0435 ??
R Medicine > RJ Pediatrics > RJ0370 Diseases of children and adolescents > RJ0499 Mental disorders of children and adolescents. Child psychiatry. Child mental health services
Depositing User: Hazelle Woodhurst
Date Deposited: 22 Aug 2011 12:49
Last Modified: 07 Mar 2017 09:10
URI: http://sro.sussex.ac.uk/id/eprint/7049
Google Scholar:63 Citations

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