This study aimed to measure, using fMRI, the effect of diazepam on the haemodynamic response to emotional faces. Twelve healthy male volunteers (mean age = 24.83 ± 3.16 years), were evaluated in a randomized, balanced-order, double-blind, placebo-controlled crossover design. Diazepam (10 mg) or placebo was given 1 h before the neuroimaging acquisition. In a blocked design covert face emotional task, subjects were presented with neutral (A) and aversive (B) (angry or fearful) faces. Participants were also submitted to an explicit emotional face recognition task, and subjective anxiety was evaluated throughout the procedures. Diazepam attenuated the activation of right amygdala and right orbitofrontal cortex and enhanced the activation of right anterior cingulate cortex (ACC) to fearful faces. In contrast, diazepam enhanced the activation of posterior left insula and attenuated the activation of bilateral ACC to angry faces. In the behavioural task, diazepam impaired the recognition of fear in female faces. Under the action of diazepam, volunteers were less anxious at the end of the experimental session. These results suggest that benzodiazepines can differentially modulate brain activation to aversive stimuli, depending on the stimulus features and indicate a role of amygdala and insula in the anxiolytic action of benzodiazepines.

Facial expressions of basic emotions have been widely used to investigate the neural substrates of emotion processing, but little is known about the exact meaning of subjective changes provoked by perceiving facial expressions. Our assumption was that fearful faces would be related to the processing of potential threats, whereas angry faces would be related to the processing of proximal threats. Experimental studies have suggested that serotonin modulates the brain processes underlying defensive responses to environmental threats, facilitating risk assessment behavior elicited by potential threats and inhibiting fight or flight responses to proximal threats. In order to test these predictions about the relationship between fearful and angry faces and defensive behaviors, we carried out a review of the literature about the effects of pharmacological probes that affect 5-HTmediated neurotransmission on the perception of emotional faces. The hypothesis that angry faces would be processed as a proximal threat and that, as a consequence, their recognition would be impaired by an increase in 5-HT function was not supported by the results reviewed. In contrast, most of the studies that evaluated the behavioral effects of serotonin challenges showed that increased 5-HT neurotransmission facilitates the recognition of fearful faces, whereas its decrease impairs the same performance. These results agree with the hypothesis that fearful faces are processed as potential threats and that 5-HT enhances this brain processing.

Serotonin has been implicated in the neurobiology of depressive and anxiety disorders, but little is known about its role in the modulation of basic emotional processing. The aim of this study was to determine the effect of the selective serotonin reuptake inhibitor, escitalopram, on the perception of facial emotional expressions. Twelve healthy male volunteers completed two experimental sessions each, in a randomized, balanced order, double-blind design. A single oral dose of escitalopram (10 mg) or placebo was administered 3 h before the task. Participants were presented to a task composed of six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) that were morphed between neutral and each standard emotion in 10% steps. Escitalopram facilitated the recognition of sadness and inhibited the recognition of happiness in male, but not female faces. No drug effect on subjective measures was detected. These results confirm that serotonin modulates the recognition of emotional faces, and suggest that the gender of the face can have a role in this modulation. Further studies including female volunteers are needed.

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Background and Aims:The aim of this study was to verify the effects of the selective serotonin reuptake inhibitor escitalopram on the recognition of facial emotional expressions.Method:Twelve healthy males completed two experimental sessions each, separated by at least 2 weeks, in a randomized, balanced order, double-blind design. An oral dose of escitalopram (10 mg) or placebo was given 3 hours before the task. Face recognition task: Subjects were presented with pictures of faces from the Pictures of Facial Affect Series (Ekman and Friesen, 1976). Faces with six basic emotions (anger, disgust, fear, happiness, sadness and surprise) had been morphed between neutral (0%) and each standard emotion (100%), in 10% steps. Accuracy was analyzed through MANOVA with repeated measures. Values of p < 0.05 were considered significant.Results:Volunteers recognized more accurately negative emotions in female faces than in male faces, whereas happiness was identified more easily in male faces. In general, the acute administration of a single dose of escitalopram increased the accuracy of the recognition of angry and sad faces. When the gender of the faces was analyzed, escitalopram facilitated the recognition of sad expressions and impaired the recognition of happy faces in male, but not in female faces. A global order effect has also been found; the administration of escitalopram in the second experimental session facilitated the recognition of emotional expressions.Conclusions:These results indicate that serotonin modulates the recognition of emotional faces. Previous experience and gender of the emotional face interact with this modulation.