The neural mechanisms by which testosterone acts on interpersonal trust

Recently, we demonstrated that the steroid-hormone testosterone reduces interpersonal trust in humans. The neural mechanism which underlies this effect is however unknown. It has been proposed that testosterone increases social vigilance via neuropeptide systems in the amygdala, augmenting communication between the amygdala and the brain stem. However, testosterone also affects connectivity between the orbitofrontal cortex (OFC) and the amygdala, which could subsequently lead to increased vigilance by reduced top-down control over the amygdala. Here, in a placebo-controlled testosterone administration study with 16 young women, we use functional magnetic resonance imaging to get more insights into neural mechanisms whereby testosterone acts on trust. Several cortical systems, among others the OFC, are involved in the evaluation of facial trustworthiness. Testosterone administration decreased functional connectivity between amygdala and the OFC during judgments of unfamiliar faces, and also increased amygdala responses specifically to the faces that were rated as untrustworthy. Finally, connectivity between the amygdala and the brain stem was not affected by testosterone administration. Although speculative, a neurobiological explanation for these findings is that in uncertain social situations, testosterone induces sustained decoupling between OFC and amygdala by a prefrontal-dopaminergic mechanism, subsequently resulting in more vigilant responses of the amygdala to signals of untrustworthiness. (c) 2012 Elsevier Inc. All rights reserved.