BackgroundThe ability to control social-emotional actions is relevant for everyday social interaction and may be indicative of responsiveness to actual social stress situations. This is particularly relevant for predicting stress responsiveness of the hypothalamic-pituitary-adrenal axis, known to be dysregulated in various stress-related affective disorders. Here we tested, in a large sample, whether reduced frontal control over social approach-avoidance actions can indeed signal increased hypothalamic-pituitary-adrenal axis reactivity to subsequent social stress exposure. MethodsA total of 279 subjects (214 men) participated in a functional magnetic resonance imaging social-emotional approach-avoidance task that involved impulsive and controlled emotional actions. Subsequently, participants underwent a stress induction including a socially evaluated cold pressor task and a mental arithmetic task. Salivary cortisol and α-amylase levels, as well as self-reported negative affect, were measured before and after stress induction. ResultsEmotion control was successfully induced by the approach-avoidance task. Namely, instrumental overriding of automatic social approach-avoidance actions was associated with the typical increased bilateral anterior prefrontal cortex activation, longer reaction times, and more errors. Moreover, subsequent stress induction led to significant increases in all stress measures. Critically, bilateral anterior prefrontal cortex activation during emotion control was associated with reduced responses to the subsequent stressor in not only cortisol but also α-amylase and negative affect. ConclusionsThe ability to recruit prefrontal regions during social-emotion regulation predicts cortisol responses to an actual social stress situation. This finding provides the first evidence that instrumental control over social approach avoidance actions can signal stress responsiveness in major stress systems, providing a promising biomarker in stress vulnerability and resilience research relevant for affective disorders.