Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing

Charles Masaki, Ann L Sharpley, Charlotte M Cooper, Beata R Godlewska, Nisha Singh, Sridhar R Vasudevan, Catherine J Harmer, Grant C Churchill, Trevor Sharp, Robert D Rogers, Philip J Cowen, Charles Masaki, Ann L Sharpley, Charlotte M Cooper, Beata R Godlewska, Nisha Singh, Sridhar R Vasudevan, Catherine J Harmer, Grant C Churchill, Trevor Sharp, Robert D Rogers, Philip J Cowen

Abstract

Rationale: Lithium remains the most effective treatment for bipolar disorder and also has important effects to lower suicidal behaviour, a property that may be linked to its ability to diminish impulsive, aggressive behaviour. The antioxidant drug, ebselen, has been proposed as a possible lithium-mimetic based on its ability in animals to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium.

Objectives: The aim of the study was to determine whether treatment with ebselen altered emotional processing and diminished measures of risk-taking behaviour.

Methods: We studied 20 healthy participants who were tested on two occasions receiving either ebselen (3600 mg over 24 h) or identical placebo in a double-blind, randomized, cross-over design. Three hours after the final dose of ebselen/placebo, participants completed the Cambridge Gambling Task (CGT) and a task that required the detection of emotional facial expressions (facial emotion recognition task (FERT)).

Results: On the CGT, relative to placebo, ebselen reduced delay aversion while on the FERT, it increased the recognition of positive vs negative facial expressions.

Conclusions: The study suggests that at the dosage used, ebselen can decrease impulsivity and produce a positive bias in emotional processing. These findings have implications for the possible use of ebselen in the disorders characterized by impulsive behaviour and dysphoric mood.

Keywords: Ebselen; Emotional processing; Impulsivity; Lithium-mimetic.

Figures

Fig. 1
Fig. 1
Results of the Cambridge Gambling Task. a Ebselen treatment was associated with a significant decrease in the mean delay aversion (main effect of treatment on ANOVA, F1, 18 = 8.208, p = 0.010). b The decrease in delay aversion following ebselen treatment was present irrespective of the token ratio presented
Fig. 2
Fig. 2
Results of the Facial Emotion Recognition Task. a There were significant interactions between treatment and emotion, for accuracy of recognition of positive and negative facial expressions (F1, 18 = 8.267, p = 0.010). Ebselen treatment was associated with a significant increase in the accuracy of recognition of positive expressions without significant effects in recognition of negative expressions. b Ebselen treatment was not associated with any significant differences in the misclassifications of emotional expressions. All data are plotted as mean ± standard error of mean, N = 20. Values represent the percentage of average total responses for positive (happy + surprise) and negative (angry + disgust + fear + sad) expressions. *p = 0.035

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Source: PubMed

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