An fMRI study of cytokine-induced depressed mood and social pain: the role of sex differences

Naomi I Eisenberger, Tristen K Inagaki, Lian T Rameson, Nehjla M Mashal, Michael R Irwin, Naomi I Eisenberger, Tristen K Inagaki, Lian T Rameson, Nehjla M Mashal, Michael R Irwin

Abstract

Although research has demonstrated a relationship between proinflammatory cytokine activity and depressive symptoms, the neurocognitive processes underlying this relationship have remained largely unexplored. Here, we examined the effect of proinflammatory cytokine activation on the neural correlates of socially painful experience and associated depressed mood. Participants received either low-dose endotoxin or placebo through intravenous injection. Levels of the proinflammatory cytokine, IL-6, were repeatedly assessed through hourly blood draws; self-reported depressed mood was assessed hourly as well. Two hours post-injection, participants completed a neuroimaging session in which they were socially excluded during an online ball-tossing game. Replicating previous research, individuals exposed to endotoxin, compared to placebo, showed increases in IL-6 levels and depressed mood. Although there were no meaningful differences between the endotoxin and control groups in neural responses to social exclusion, there were sex differences in the relationships between IL-6 increases and neural responses to exclusion among subjects exposed to endotoxin. Among females, but not males, exposed to endotoxin, increases in IL-6 were associated with increases in social pain-related neural activity (dorsal anterior cingulate cortex, anterior insula) that mediated the relationship between IL-6 increases and depressed mood increases. Implications of these sex differences in the neural correlates of cytokine-associated depressed mood and social pain are discussed.

Figures

Figure 1
Figure 1
Changes over time in: A) plasma levels of IL-6 (these are raw values that have not been log-transformed) and B) self-reported depressed mood. Time points with asterisks indicate significant time X condition interactions. These figures are published separately and have been adapted from Eisenberger et al., (2009).
Figure 2
Figure 2
Neural activity that correlated positively with increases in IL-6 levels (from baseline to immediately prior to the neuroimaging session) during exclusion vs. inclusion for the endotoxin subjects: A) Activity in the bilateral insula and B) Activity in the medial prefrontal cortex (MPFC) and posterior superior temporal sulcus (pSTS).
Figure 3
Figure 3
Activity in the A) Dorsal anterior cingulate cortex (dACC; -8, 22, 46) and B) bilateral anterior insula (left: -22, 32, 4; right: 42, 22, -2) that correlated with increases in IL-6 levels from baseline to two-hours post-injection among females in the endotoxin group. Scatterplots showing the relationship between C) dACC activity and D) right anterior insula activity with increases in depressed mood from baseline to two-hours post-injection among females in the endotoxin group.

Source: PubMed

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