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

• Published in: NeuroImage (Orlando, Fla.) Vol. 47; no. 3; pp. 881 - 890
• Main Authors: Eisenberger, Naomi I., Inagaki, Tristen K., Rameson, Lian T., Mashal, Nehjla M., Irwin, Michael R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2009; Elsevier Limited
• Subjects: Adolescent; Adult; Blood-brain barrier; Brain Mapping; Brain research; Correlation; Cytokines; Cytokines - blood; Depression - blood; Depression - immunology; Depression - physiopathology; Endotoxins; Endotoxins - immunology; Estradiol - blood; Exposure; Female; Games; Humans; Hydrocortisone - blood; Image Processing, Computer-Assisted; Interleukin-6 - blood; Magnetic Resonance Imaging; Male; Mental depression; Moods; Pain; Progesterone - blood; Rodents; Sex; Sex Characteristics; Social exclusion; Social Isolation; Studies; Young Adult
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2009.04.040

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.