Moderators for depressed mood and systemic and transcriptional inflammatory responses: a randomized controlled trial of endotoxin.

Activation of the innate immune system is thought to contribute to depression. Multiple social and behavioral factors are also known to instigate depression. Whether these socio-behavioral factors interact with inflammatory stimuli to alter proinflammatory responses and depressed mood is not known. In 115 healthy adults, social, emotional, and behavioral factors were assessed at baseline. A single infusion of endotoxin (Escherichia coli; 0.8 ng/kg of body weight) or placebo (0.9% saline) was administered with hourly assessment of depressed mood and proinflammatory cytokines (interleukin-6 (IL-6); tumor necrosis factor-α (TNF)). Inflammatory gene expression was examined at 30 min after infusion, prior to increase of inflammatory cytokines. As compared to placebo, endotoxin-induced increases of depressed mood were moderated by baseline levels of perceived stress, trait sensitivity to social disconnection, and severity of symptoms of anxiety and depression (all Ps < 0.05) but not early life stress, social status, social support, neuroticism, or sleep disturbance. Anxiety symptoms remained significant in multivariable analyses (P < 0.01). None of these socio-behavioral factors were related to increases in proinflammatory cytokines. Transcriptome profiling analyses indicated that perceived stress, sensitivity to social disconnection, and depressive symptoms were associated with increased activation of pro-inflammatory transcription control pathways (i.e., activator protein-1, nuclear factor-κB) in response to endotoxin (all Ps < 0.05). These results indicate that an array of socio-behavioral factors, which are associated with depression risk, modify vulnerability to inflammation-induced depressed mood. Together, these observations may be used to help target therapeutic interventions to mitigate occurrence of the inflammatory biotype of depression.

RCT Entities:   Population Interventions Outcomes