Abstract
Rationale Stress is associated with increased sensitivity to threat. Previous investigations examining how stress affects threat processing have largely focused on biomarker responses associated with either the sympathetic-nervous-system (SNS) or the hypothalamus-pituitary-adrenal (HPA) axis. Objectives We pharmacologically suppressed activations of SNS, HPA, or both, prior to stress and investigated how each stress system modulates social threat assessment. Methods One hundred sixty-one healthy men and women were randomized in a between-subject design, to one of four pharmacological or placebo conditions: dexamethasone–placebo, placebo–propranolol, dexamethasone–propranolol, or placebo–placebo. Participants provided threat assessments for angry and neutral human faces on a baseline day, and immediately after stress induction on a testing day. Results With both systems responding normally to stress (placebo–placebo), threat assessment was higher for neutral faces compared with angry. Compared with placebo, SNS suppression resulted in increased threat assessment for angry faces. HPA suppression resulted in decreased threat assessment for neutral and angry faces. When both systems were suppressed, there was an increase in threat assessment for angry faces, and no difference from placebo for neutral. Conclusion Our findings demonstrated that when intact, the biological stress systems adaptively support organisms during stress by focusing attention towards specific stimuli that are relevant to the threat. Dysregulations of the stress systems result in important system specific consequences on threat evaluation, such that suppression of either stress system alone resulted in reduced threat assessment for contextually relevant threatening stimuli, whereas when both systems were suppressed, individuals appear indiscriminately attentive to all potential threats in the environment, resulting in increased threat processing of both contextually relevant and irrelevant stimuli. Given that stress-related psychopathologies have been associated with dysregulations of the stress systems and biased responses to social threat, a systematic understanding of the mechanisms that underlie how stress systems modulate social threat assessment is needed, and can provide important insights into the cognitive processes that are involved in the development and maintenance of stress-related psychopathologies.