Moderators for depressed mood and systemic and transcriptional inflammatory responses: a randomized controlled trial of endotoxin.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 30391995 · doi:10.1038/s41386-018-0259-6
What was done
In 115 healthy adults, baseline social, emotional, and behavioral factors were assessed before participants received a single infusion of either endotoxin (Escherichia coli; 0.8 ng/kg) or placebo (0.9% saline). Depressed mood and systemic proinflammatory cytokines (IL-6, TNF) were measured hourly. Inflammatory gene expression and transcription control pathways (AP-1, NF-κB) were evaluated from transcriptome profiles 30 minutes post-infusion.
What was found
Compared to placebo, endotoxin-induced increases in depressed mood were moderated by baseline perceived stress, trait sensitivity to social disconnection, anxiety symptoms, and depressive symptoms (all P < 0.05). Anxiety symptoms remained significant in multivariable analyses (P < 0.01). Early life stress, social status, social support, neuroticism, and sleep disturbance did not moderate mood responses. None of the socio-behavioral factors related to increases in circulating cytokines. Perceived stress, social disconnection sensitivity, and depressive symptoms were associated with increased activation of AP-1 and NF-κB transcription control pathways in response to endotoxin (all P < 0.05). Exact effect sizes and group breakdowns were not reported in the abstract.
Why it matters
This study indicates that specific psychological and social vulnerabilities amplify mood and inflammatory transcriptional reactivity following an acute inflammatory stimulus, helping explain differential susceptibility to inflammation-associated depression.
Limits
The study tested an acute, transient endotoxin challenge in healthy adults rather than chronic clinical depression or sustained systemic inflammation. Exact numerical values, confidence intervals, and group sample sizes were not provided in the abstract.
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