Abstract

The ability to interpret someone’s mental state such as their emotions and intentions (denoted Theory of Mind, ToM), is key to human social interaction. This ability is impaired in several psychopathologies including major depression, and inflammation has been proposed as a candidate mechanism of such impairments. Experimental studies using LPS injection support a role of inflammation, but LPS-induced symptoms of sickness could themselves cause the observed reductions in ToM behaviors. Here we experimentally replicated these effects using a manipulation that minimized these potentially confounding side-effects. Forty healthy male participants (mean age = 25, SD= 5) completed the Reading the Mind in the Eyes Test (a measure of ToM) in this double-blind placebo-controlled within-subjects crossover triaI. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur) and saline-injection was used as a control. IL-6 was used as a marker of inflammation. Vaccination increased IL-6 levels (+419%, p .001), without inducing fever or sickness symptoms (e.g., nausea), or mood changes (all p > .10). The results showed that typhoid vaccination significantly reduced ToM performance compared to placebo (M = 71%, SD = 13%’ placebo M = 65%, SD = 13%; p .05). The present findings provide further support for the idea that emotion recognition is impaired during immune activation. Inflammation may in part drive social-cognitive deficits in pathologies that exhibit enhanced inflammation, such as major depression.

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