Direct effects of diazepam on emotional processing in healthy volunteers

Abstract

Rationale: Pharmacological agents used in the treatment of anxiety have been reported to decrease threat relevant processing in patients and healthy controls, suggesting a potentially relevant mechanism of action. However, the effects of the anxiolytic diazepam have typically been examined at sedative doses, which do not allow the direct actions on emotional processing to be fully separated from global effects of the drug on cognition and alertness.

Objectives: The aim of this study was to investigate the effect of a lower, but still clinically effective, dose of diazepam on emotional processing in healthy volunteers.

Materials and methods: Twenty-four participants were randomised to receive a single dose of diazepam (5 mg) or placebo. Sixty minutes later, participants completed a battery of psychological tests, including measures of non-emotional cognitive performance (reaction time and sustained attention) and emotional processing (affective modulation of the startle reflex, attentional dot probe, facial expression recognition, and emotional memory). Mood and subjective experience were also measured.

Results: Diazepam significantly modulated attentional vigilance to masked emotional faces and significantly decreased overall startle reactivity. Diazepam did not significantly affect mood, alertness, response times, facial expression recognition, or sustained attention.

Conclusions: At non-sedating doses, diazepam produces effects on attentional vigilance and startle responsivity that are consistent with its anxiolytic action. This may be an underlying mechanism through which benzodiazepines exert their therapeutic effects in clinical anxiety.

Fig. 1

Attentional vigilance in the attentional probe task in the masked condition (upper) and the unmasked condition (lower). Vigilance is calculated by subtracting mean reaction time to respond when probe replaces emotional face (fearful or happy) from the reaction time when the probe replaces the neutral face. Thus, the higher the vigilance score, the greater the attentional bias towards the emotional face. Error bars represent standard error of mean. Only values from correct trials are displayed. *p < 0.05

Fig. 2

Startle eye-blink responses to a burst of white noise presented during the presentation of neutral (light grey), pleasant (black) and unpleasant (dark grey) pictures. Both groups demonstrated increased startle amplitude in the unpleasant condition relative to the pleasant and neutral conditions. Startle responses were significantly reduced in the diazepam group compared to the placebo group, irrespective of the picture stimuli presented. Error bars represent standard error of mean. *p < 0.05