Enhancement of serotonin neurotransmission plays an important role in the antidepressant response to agents presently available to treat depression. This response forms the major evidence for the role of serotonin in affective and social behaviour in humans. The present study investigated the effects of acute administration of the selective serotonin reuptake inhibitor (SSR1), citalopram (10 mg, i.v.) upon a measure of emotional processing in healthy female volunteers. Subjects completed a facial expression recognition task following infusion of citalopram or saline (between-subjects design, double-blind). Facial expressions associated with five basic emotionsFhappiness, sadness, fearfulness, anger and disgustFwere displayed. Each face had been 'morphed' between neutral (0%) and each emotional standard (100%) in 10% steps, leading to a range of emotional intensities. Mood and subjective experience were also monitored throughout the testing session. Volunteers receiving citalopram detected a higher number of facial expressions of fear and happiness, with reduced response times, relative to those given the placebo. By contrast, changes in the recognition of other basic emotions were not observed following citalopram. Notable differences in mood were also not apparent in these volunteers. These results suggest that acute administration of antidepressant drugs may affect neural processes involved in the processing of social information. This effect may represent an early acute effect of SSRIs on social and emotional processing that is relevant to their therapeutic actions.

These results confirm a role for serotonin in the processing of fear related cues, and in line with previous findings also suggest greater effects of tryptophan depletion in female volunteers. Although acute tryptophan depletion does not typically affect mood in healthy subjects, the present results suggest that subtle changes in the processing of emotional material may occur with this manipulation of serotonin function.

Depression is a leading cause of disability worldwide and improving its treatment is a core research priority for future programmes. A change in the view of psychological and biological processes, from seeing them as separate to complementing one another, has introduced new perspectives on pathological mechanisms of depression and treatment mode of action. This review presents a theoretical model that incorporated this novel approach, the cognitive neuropsychological hypothesis of antidepressant action. This model proposes that antidepressant treatments decrease the negative bias in the processing of emotionally salient information early in the course of antidepressant treatment, which leads to the clinically significant mood improvement later in treatment. The paper discusses the role of negative affective biases in the development of depression and response to antidepressant treatments. It also discusses whether the model can be applied to other antidepressant interventions and its potential translational value, including treatment choice, prediction of response and drug development.