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
Date Published2010 Oct 15
KeywordsAdolescent, Adult, Basal Ganglia, Cytokines, Depression, Endotoxins, Female, Humans, Inflammation, Magnetic Resonance Imaging, Male, Placebos, Pleasure, Reward

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.

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