Serotonergic Modulation of Cognition, Emotion and Brain Activation in Healthy Volunteers
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this project is:

        -  To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT
           system) reuptake inhibition in healthy humans. Specifically:

        -  To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive
           performance ('cold' cognition) and social-emotional functioning ('hot' cognition)
           compared with placebo; and

        -  To investigate how sub-chronic administration of 20 mg of escitalopram affects
           functional brain activation during a paradigm of reinforcement learning following drug
           administration compared with placebo, and how activation relates to cognitive
           performance and social-emotional functioning.
    

Detailed description: 
      The aim of this project is:

        -  To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT
           system) reuptake inhibition in healthy humans. Specifically:

        -  To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive
           performance ('cold' cognition) and social-emotional functioning ('hot' cognition)
           compared with placebo; and

        -  To investigate how sub-chronic administration of 20 mg of escitalopram affects
           functional brain activation during a paradigm of reinforcement learning following drug
           administration compared with placebo, and how activation relates to cognitive
           performance and social-emotional functioning.

      Serotonin is a monoamine neurotransmitter implicated in diverse cognitive and affective brain
      functions. Serotonin has a significant role in the regulation of cognition and mood,
      including emotional appraisal, perception and flexible behaviour, with 5-HT receptors found
      in the cortex, amygdala and hippocampus. The investigators have previously shown that in
      healthy human experimental studies, acute dietary tryptophan depletion induces 'waiting'
      impulsivity and impulsive behaviours, impairs goal-directed behaviour and shifts behavioural
      control toward habitual responding when appetitive, but goal-directed when aversive. Reduced
      availability of forebrain serotonin has also shown to impair a range of cognitive processes,
      such as psychomotor processing, episodic memory, attention and executive function. Recently,
      the research team have shown that using an acute and clinically relevant dose (20 mg) of
      escitalopram impaired learning and cognitive flexibility, but improved response inhibition in
      healthy humans, suggesting a dissociation of effects possibly mediated by differential
      modulation of brain serotonin levels in distinct functional neural circuits.

      The investigators now aim to investigate the effects of sub-chronic administration of 20 mg
      of escitalopram (i.e. three weeks) in healthy volunteers using sophisticated
      neuropsychological testing (Cambridge Neuropsychological Test Automated Battery and EMOTICOM)
      and functional magnetic resonance imaging (fMRI). Whereas 'cold' cognition refers to the use
      of non-emotional processing (e.g. episodic memory; spatial working memory), 'hot' cognition
      is emotion-laden and used in response to stimuli with affective salience (e.g.
      decision-making under high levels of risk of uncertainty). It has been suggested that
      cognitive-emotional effects, such as the re-appraisal and re-evaluation of emotions
      underlying learning mechanisms, may mediate improvements in mood associated with SSRI
      treatment. This project will help further the understanding of the role of serotonin in the
      regulation of cognitive and emotional processes, as well the neural correlates underlying
      reinforcement learning, in healthy humans.
    

Intervention name(s): Escitalopram 20 mg; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 20mg daily for approximately 3 weeks.; Placebo daily for approximately 3 weeks.
Intervention MeSH terms: Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Serotonin; Cognition; Emotion; Neural Activation