Escitalopram effects on insula and amygdala BOLD activation during emotional processing

Abstract

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 administration 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 participated 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 pharmacological probes to help identify the specific therapeutic effect of these agents in patients with anxiety and mood disorders.

Figure 1

Flowchart of study participants.

Figure 2

Study design

Figure 3

Extraction of percent signal change in anatomically defined regions of interest during all faces types – all shape types, for each treatment condition.

Figure 4

Brain areas that significantly correlated with regions of interest related to urine concentration levels during escitalopram administration in 13 subjects.

Figure 5. Amygdala attenuation due to sub-chronic escitalopram administration in 10 subjects

Note: Brain regions depicted in the figure resulted from between-conditions (Placebo vs Escitalopram) Fearful-Oval Contrast in 10 subjects. Areas were masked onto Happy-Oval and Angry-Oval contrasts to obtain the above % signal change.