Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.

TitleInflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.
Publication TypeJournal Article
Year of Publication2010
AuthorsEisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR
JournalBiol Psychiatry
Volume68
Issue8
Pagination748-54
Date Published2010 Oct 15
ISSN1873-2402
KeywordsAdolescent, Adult, Basal Ganglia, Cytokines, Depression, Endotoxins, Female, Humans, Inflammation, Magnetic Resonance Imaging, Male, Placebos, Pleasure, Reward
Abstract

BACKGROUND: Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood.

METHODS: Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards.

RESULTS: Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward.

CONCLUSIONS: The data reported here show, for the first time, that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood. As such, these findings have implications for understanding risk of depression in persons with underlying inflammation.

DOI10.1016/j.biopsych.2010.06.010
Alternate JournalBiol. Psychiatry
PubMed ID20719303
PubMed Central IDPMC3025604
Grant ListAG-026364 / AG / NIA NIH HHS / United States
CA-10014152 / CA / NCI NIH HHS / United States
CA-116778 / CA / NCI NIH HHS / United States
F31 DA024904 / DA / NIDA NIH HHS / United States
F31 DA024904-02 / DA / NIDA NIH HHS / United States
HL-079955 / HL / NHLBI NIH HHS / United States
M01-RR00865 / RR / NCRR NIH HHS / United States
P30 AG028748 / AG / NIA NIH HHS / United States
P30-AG028748 / AG / NIA NIH HHS / United States
T32-MH19925 / MH / NIMH NIH HHS / United States