Lithium Effects on Reward Processing and Reappraisal in Healthy Volunteers

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.