Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to 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.
Eisenberger
Naomi I
NI
Department of Psychology, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, California 90095-1563, USA. neisenbe@ucla.edu
Berkman
Elliot T
ET
Inagaki
Tristen K
TK
Rameson
Lian T
LT
Mashal
Nehjla M
NM
Irwin
Michael R
MR
D000293:Adolescent; D000328:Adult; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood; D003863:Depression / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000523:psychology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010919:Placebos; D057181:Pleasure / Q000187:drug effects / Q000502:physiology*; D012201:Reward
D016207:Cytokines; D004731:Endotoxins; D010919:Placebos; C044101:endotoxin, Escherichia coli