Prednisolone increases neural reactivity to negative socio-emotional stimuli in healthy young men

• Prednisolone increased amygdala reactivity to emotional scenes, and this was related to lower fatigue and higher irritability.
• Prednisolone also heightened reactivity to negative emotional stimuli in inferior frontal gyrus, somatosensory cortex, caudate, and supplementary motor area.
• Prednisolone decreased inferior frontal and amygdala connectivity with other emotion-processing areas when watching negative scenes.

Exogenous glucocorticoids are known to trigger affective changes, but these are highly variable across individuals. A better understanding of how synthetic glucocorticoids impact the processing of negative emotions in the human brain might help to predict such changes. In the present functional magnetic resonance imaging (fMRI) study, we sought to uncover the slow effects of a synthetic glucocorticoid infusion on the neural response to socio-emotional scenes using a within-participant, double-blind, placebo-controlled design. In two separate sessions, 20 young males were given either an intravenous prednisolone dose (250 mg) or placebo in a cross-over, randomized order. Four hours later, they were scanned while viewing drawings of persons in a neutral or negative emotional situation. On the next morning participants provided a blood sample for serum cortisol measurement, which served as a manipulation check. Prednisolone strongly suppressed morning cortisol, and heightened brain reactivity to emotional stimuli in left amygdala, left caudate head, right inferior frontal gyrus, bilateral supplementary motor area, and right somatosensory cortex. Amygdala reactivity was related to lower self-reported fatigue and higher irritability in the prednisolone condition. Moreover, prednisolone blunted inferior frontal and amygdala connectivity with other regions of the emotion-processing neural circuitry. Our results suggest specific brain pathways through which exogenous glucocorticoids may labilize affect.