52. Dose-dependent effects of lipopolysaccharide on memory and social cognition in humans

Abstract

Clinical and experimental studies demonstrate that inflammation and increased concentrations of pro-inflammatory cytokines are associated with depression-like symptoms and neuropsychological impairments in humans. However, it has not been satisfactorily elucidated to what extent cognitive functions such as memory, attention or social cognition are affected during systemic immune activation. Thus, in a double-blind, randomized, placebo-controlled crossover study, healthy male subjects received intravenous injections of either lipopolysaccharide (low-dose LPS: 0.4 ng/kg, n = 18; high-dose LPS: 0.8 ng/kg, n = 16) or placebo (0.9% saline) on two different study days. Memory (n-back; visual long-term memory task) and social cognition performance (MASC; Reading-the-Mind-in-the-Eyes-Test) were assessed 2–4 h after LPS or saline injection. LPS administration dose-dependently elevated body temperature and plasma concentrations of TNF-alpha, IL-6, IL-10, and IL-1ra and increased negative mood and state anxiety. However, endotoxin administration did not affect accuracy in a working memory paradigm but improved reaction time after high-dose LPS administration. In contrast, long-term memory performance was impaired selectively for emotional stimuli after administration of low-dose LPS only. Finally, there was a significant, albeit relatively small, effect on social cognition after injection of the high-dose LPS. Taken together, this study demonstrates that acute systemic inflammation mildly affects but not necessarily impairs cognitive functions in humans.