Lithium Effects on Reward Processing and Reappraisal in Healthy Volunteers
Condition: Healthy
Study type: Interventional

Summary: 
      Bipolar disorder has been associated with blunted activity in regions associated with
      emotional processing, such as striatal activity during reward anticipation as well as
      prefrontal activity during reappraisal. Lithium is the most effective treatment in bipolar
      disorder. Neurochemical and molecular basis of lithium is well known, but how this translates
      to mood stabilisation is not understood. This study is designed to address how lithium
      influences reward and emotion regulation processes in humans.
    

Detailed description: 
      Background:

      Bipolar disorder is a relatively common psychiatric disorder for which treatment options are
      limited. The so-called mood stabiliser, lithium (usually in the form of lithium carbonate) is
      one of the most commonly used treatments for the disorder, and is effective in treating both
      acute mania and as a long term maintenance treatment. The investigator's understanding of the
      pharmacological mechanisms by which lithium exerts its actions is fairly well developed,
      however there is a lack of understanding of the psychological mechanisms. Within this study
      the investigators will look at two different types of emotional processing, namely reward
      anticipation/feedback and emotion regulation, to gain more understanding on how lithium
      exerts its mood stabilising effects.

      Reward processing:

      The neural correlates underlying reward anticipation and feedback can be measured with the
      Monetary Incentive Delay (MID) task, a widely used task for different disorders. Reward
      anticipation during the MID task has been associated among others, with ventral and dorsal
      striatum activity. Most critically, bipolar disorder has been associated with blunted reward
      function of the medial caudate. Reward feedback has been associated with ventral striatum and
      OFC/vmPFC activity.

      Emotion regulation:

      One of the most prominent approaches of emotion regulation is reappraisal . Reappraisal has
      been shown to consistently activate cognitive control regions and to modulate the bilateral
      amygdala. Insufficient prefrontal control and reduced downregulation of those prefrontal
      regions of the amygdala while reappraising negative stimuli has been consistently found in
      bipolar disorder.

      Methods:

      Using a double-blind, parallel-group design, 37 healthy volunteers (male and female) are
      randomly allocated to a 11 (+/- 1) day lithium administration or a placebo condition. After
      the intervention period, all participants undergo fMRI testing with the MID task and the
      emotional suppression task to assess reward processing and reappraisal of negative stimuli.
      The participants also complete a visual control task (checkerboard task) and several
      behavioural tasks and questionnaires. Lithium levels are measured at the end of the
      intervention period.

      Hypothesis:

      Based on the literature on bipolar disorder and the mood stabilising effects of Lithium, the
      investigators expect lithium administration in healthy participants to:

        -  Increase caudate activity during reward anticipation

        -  Increase activation of prefrontal control regions as well as increase negative
           connectivity between those regions and the amygdala during reappraisal

      Fidelity check: significant increases in lithium levels in the lithium intervention group
      compared to the placebo group.
    

Intervention name(s): Lithium; Placebo - Rayotabs
Intervention type(s): Drug; Other
Other intervention name(s): Priadel; Lithium carbonate
Intervention MeSH terms: Lithium Carbonate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants were randomly assigned to the placebo or lithium group. The two groups were matched in terms of age and gender.
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Lithium; Reward; Caudate; Reappraisal; Prefrontal cortex; Amygdala