Behavioral, cortical and autonomic effects of single-dose escitalopram on the induction and regulation of fear and disgust: Comparison with single-session psychological emotion regulation with reappraisal

Abstract

Introduction: Adaptive and successful emotion regulation, the ability to flexibly exert voluntary control over emotional experience and the ensuing behavior, is vital for optimal daily functioning and good mental health. In clinical settings, pharmacological and psychological interventions are widely employed to modify pathological emotion processing and ameliorate its deleterious consequences.

Methods: In this study, we investigated the acute effects of single-dose escitalopram on the induction and regulation of fear and disgust in healthy subjects. Furthermore, we compared these pharmacological effects with psychological emotion regulation that utilized a cognitive strategy with reappraisal. Emotion induction and regulation tasks were performed before and 4 h after ingestion of placebo or 10 mg escitalopram in a randomized, double-blind design. The International Affective Picture System (IAPS) was used as a source of images, with threat-related pictures selected for fear and disease and contamination-related pictures for disgust. Behavioral data, electrodermal activity (EDA), and functional near-infrared spectroscopy (fNIRS) recordings were collected.

Results: Escitalopram significantly reduced emotion intensity for both fear and disgust during emotion induction, albeit with differing electrodermal and hemodynamic activity patterns for the two negative emotions. At rest, i.e., in the absence of emotive stimuli, escitalopram increased sympathetic activity during the fear but not during the disgust experiments. For both fear and disgust, emotion regulation with reappraisal was more effective in reducing emotion intensity compared to pharmacological intervention with escitalopram or placebo.

Discussion: We concluded that emotion regulation with reappraisal and acute administration of escitalopram, but not placebo, reduce emotion intensity for both fear and disgust, with cognitive regulation being significantly more efficient compared to pharmacological regulation under the conditions of this study. Results from the fNIRS and EDA recordings support the concept of differential mechanisms of emotion regulation that could be emotion-specific.

Keywords: EDA; SSRI; disgust; emotion induction; emotion regulation; escitalopram; fNIRS; fear.

FIGURE 1

(A,B) Paradigm timing for each task (fear and disgust). Each task included six blocks of stimuli (IMG), each block was 40-s long and was preceded by a 30-s long period of REST (FS). In each block, five different visual emotive stimuli (pictures IMG1-5) were presented on the screen, each for six seconds, followed by a two-seconds long interval to separate them from each other. Immediately after viewing the pictures, the subjects were asked to score emotion intensity for every image in a scale ranging from 1 to 9 during emotion induction (EI) and emotion regulation (ER). The identical procedure was repeated four hours after the ingestion of escitalopram or placebo (intervention phase). The order of the images, conditions and tasks was randomized. (C) Shows the fNIRS channel locations on the PFC. The data were averaged over left (LPFC, channels 1-6), medial (MPFC, channels 7-10) and right (RPFC, channels 11-16) prefrontal regions to increase signal-to-noise ratio.

FIGURE 2

Behavioral measures (A) change of subjective rating of emotion intensity from baseline (control) after pharmacological intervention with escitalopram and placebo, respectively. For both fear and disgust, escitalopram significantly reduced emotion induction, whereas placebo had no significant effect (shown mean difference and SE in score in a scale 1-9, significance asterisk declare significance related to 0). (B) Change of subjective rating of emotion intensity while applying reappraisal before (control) and after pharmacological intervention with escitalopram and placebo, respectively. (C) Effortful emotion regulation with reappraisal (operationalized as psychological ER index) was associated with a mean decrease of ca 45% in emotion induction of both fear and disgust. This reduction was significantly larger than the one associated with one dose escitalopram (operationalized as pharmacological ER index) under the conditions of this study.

FIGURE 3

fNIRS recordings. Differences in Δoxy-Hb levels during emotion induction (EI) [EI – REST] for fear (A) and disgust (B); significantly greater activations compared to the control phase were seen in right PFC for fear after escitalopram was administered, whereas significantly less activation in medial and lateral PFC was seen in disgust. (C) Differences in Δoxy-Hb levels during EI [EI – REST] when comparing the two emotions after escitalopram administration show greater activation of lateral PFC in fear compared to disgust. (D) Direct contrast psychological emotion regulation (reappraisal) [ER contrast in control] with pharmacological emotion regulation (escitalopram) [EI contrast in Intervention phase, escitalopram] in fear demonstrated greater activation for the latter in right PFC, with no PFC areas found to be significantly more activated by reappraisal compared to escitalopram. No significant differences were found for disgust.

FIGURE 4

Autonomic measures (electrodermal activity – EDA frequency). (A) Fear, emotion induction. (B) Disgust, emotion induction. (C) Fear, emotion regulation. (D) Disgust, emotion regulation. The EDR labeling in the Y-axon includes both spontaneous NS-EDR (Rest columns) and stimulus-evoked EDR (EI and ER columns). (A,B) The dotted line comparisons in A (fear) and B (disgust) show that compared to control phase, after ingestion of escitalopram, a roughly 30% increase in electrodermal response frequency was measured at rest (absence of emotive stimuli) during the fear experiments but not the disgust ones. (A–D) The solid line comparisons show that, similarly to what was previously reported in a study without pharmacological intervention (61), placebo was associated with no difference between task EDA and rest in fear (A,C) but lower than rest in disgust (B,D). This pattern was reversed in the escitalopram arm, where task EDA was significantly lower than rest in fear (A,C) but not significantly different than rest in disgust (B,D). Shown mean EDA frequency, EDR per second, and SD. (E) Emotion regulation with reappraisal and escitalopram did not differ significantly regarding the effects on EDA. Shown mean change in EDA frequency (EDR per second) and SE of this difference. ***p < 0.001, **p < 0.01, and *p < 0.05. Pharmacological ER = (EDA EI in control – EDA EI in intervention phase)/EDA EI in control. Psychological ER = (EDA EI in control – EDA ER in control phase)/EDA EI in control (all adjusted to baseline/EDA rest).