Mood disturbance during experimental endotoxemia: Predictors of state anxiety as a psychological component of sickness behavior

•LPS administration is well-established to assess behavioral aspects of inflammation.•We analyzed predictors of LPS-induced state anxiety in a large pooled sample.•LPS-induced state anxiety increase was predicted by greater cytokine responses.•Pre-existing anxiety symptoms predicted a lower increase in state anxiety.•Our findings support a role of inflammation in the pathophysiology of anxiety.

Lipopolysaccharide (LPS) administration is a well-established model to assess afferent immune-to-brain communication and behavioral aspects of inflammation. Nevertheless, only few studies in comparatively small samples have assessed state anxiety as a psychological component of sickness behavior despite possible clinical implications for the pathophysiology of neuropsychiatric conditions. Thus, the goal of the present analyses carried out in a large, pooled dataset from two independent study sites was to analyze the state anxiety response to LPS administration and to investigate predictors (i.e., cytokine changes; pre-existing anxiety and depression symptoms assessed with the Hospital Anxiety and Depression Scale) of the LPS-induced state anxiety changes at different time points after LPS administration. Data from 186 healthy volunteers who participated in one of six randomized, placebo-controlled human studies involving intravenous administration of LPS at doses of 0.4-0.8 ng/kg body weight were combined. State anxiety as well as circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 concentrations were significantly increased 2 h and 3 h after LPS administration, with a peak at 2 h, and returned to baseline 6 h after administration. Greater changes in IL-6 from baseline to 3 h after LPS administration significantly and independently predicted a more pronounced LPS-induced state anxiety response. In addition, higher pre-existing subclinical anxiety symptoms significantly predicted a lower increase in state anxiety 3 h and 6 h after LPS-administration, which was mediated by TNF-α changes. In conclusion, our findings give additional support for a putative role of inflammatory mechanisms in the pathophysiology of stress-related and anxiety disorders and give new insight on the potential role of pre-existing subclinical affective symptoms.