The effect of cortisol on emotional responses depends on order of cortisol and placebo administration in a within-subject design.

Cortisol does not exhibit a straightforward relationship with mood states; administration of glucocorticoids to human subjects has produced mixed effects on mood and emotional processing. In this study, participants (N=46) received intravenous hydrocortisone (synthetic cortisol; 0.1mg/kg body weight) and placebo in randomized order over two sessions 48h apart. Following the infusion, participants rated neutral and unpleasant pictures. In Session 1, participants reported elevated negative affect (NA) following the picture-rating task, regardless of treatment. In Session 2, however, only participants who received cortisol (and thus who had received placebo in Session 1) reported elevated NA. Arousal ratings for unpleasant pictures followed a similar pattern. These findings suggest that the effects of cortisol on emotion vary based on situational factors, such as drug administration order or familiarity with the tasks and setting. Such factors can influence cortisol's effects on emotion in two ways: (A) cortisol may only potentiate NA and arousal ratings in the absence of other, overwhelming influences on affect, such as the novelty of the setting and tasks in Session 1; and (B) cortisol in Session 1 may facilitate learning processes (e.g., habituation to the stimuli and setting; extinction of aversive responses) such that emotional responses to the pictures are lessened in Session 2. This interpretation is compatible with a body of literature on the effects of glucocorticoids on learning and memory processes.