Facilitation of emotion regulation with a single dose of escitalopram: A randomized fMRI study

• Behavioral evidence suggests that effective antidepressants facilitate reappraisal.
• We examine the neural mechanism underpinning antidepressant effects on reappraisal.
• Escitalopram facilitated a key neural pathway during reappraisal.
• Neural changes were associated with decreased emotional intensity ratings.
• Findings provide important leads for models of antidepressant action.

Acute antidepressant administration modulates neural activity consistent with decreases in negative emotion processing bias. However, studies are yet to examine whether treatment facilitates neural activity during reappraisal, an adaptive emotion regulation strategy associated with behavioral treatment response. Here we examine the impact of acute administration on reappraisal of negative stimuli using pharmaco-fMRI. Thirty-six healthy female participants completed two sessions of fMRI scanning, separated by a one-week washout period. A single dose of the selective serotonin reuptake inhibitor, escitalopram (20 mg) was administered to participants using a double-blind, randomized, placebo-controlled crossover design. When participants were administered escitalopram (relative to a placebo) and asked to reappraise negative emotional stimuli, left amygdala activation was decreased and right inferior frontal gyrus (R IFG) activation was increased. Also observed was a greater negative left amygdala-R IFG functional connectivity when participants were administered escitalopram relative to placebo, and this change in connectivity was associated with reductions in subjective ratings of valence and arousal of negative stimuli. Further analysis revealed connectivity modulation across multiple frontal regions. Results suggest that the acute effect of a commonly prescribed antidepressant may include facilitating the regulation of negative emotional stimuli, providing new important leads for models of antidepressant action.