ORIGINAL INVESTIGATION Escitalopram effects on insula and amygdala BOLD activation during emotional processing

Rationale The amygdala and insular cortex are integral to the processing of emotionally salient stimuli. We have shown in healthy volunteers that an anxiolytic agent, lorazepam, dose-dependently attenuates activation of limbic structures. Objective The current study investigated whether adminis-tration of a selective serotonin reuptake inhibitor (SSRI), escitalopram, alters the activation of limbic structures. We hypothesized that subchronic (21 days) SSRI treatment attenuates the activation of the amygdala and insula during processing of emotional faces. Materials and methods Thirteen healthy volunteers partic-ipated in a double-blind, placebo-controlled, crossover, randomized study. After 21 days of treatment with either escitalopram or placebo, participants underwent functional magnetic resonance imaging (fMRI) during which all subjects completed an emotion face assessment task, which has been shown to elicit amygdala and insula activation. Results Subjects activated the bilateral insula and amygdala after treatment with both escitalopram and placebo. In subjects who were adherent to the protocol (as evidenced by sufficiently high urine concentrations of escitalopram), a reduction in amygdala activation was seen in the escitalopram condition compared to placebo. Conclusion The current investigation provides further evidence for the mechanism of action of SSRIs through the attenuation of activation in brain regions responsible for emotion processing and provides support for the use of blood oxygenation level-dependent fMRI with pharmaco-logical probes to help identify the specific therapeutic effect of these agents in patients with anxiety and mood disorders