Bipolar symptoms and lithium treatment affect neural signatures of adaptation of risk-taking to past outcomes during reward-guided decision-making

Abstract

AbstractIntroductionMood instability in bipolar disorder (BD) is poorly understood. Here we examined cognitive and neural mechanisms related to these fluctuations and how they are changed with the mood stabilizer lithium.MethodsWe recruited volunteers with low (n=37) or high (n=40) risk of BD (using the Mood Disorder Questionnaire, MDQ). We also recruited patients with BD who were assigned (randomized, double-blind) to six weeks of lithium (n=19) or placebo (n=16) after a two-week baseline period. Participants completed mood ratings daily over 50 (healthy) or 42 (BD) days, as well as a risky decision-making task and one functional magnetic resonance imaging session. The task measured adaptation of risk taking to past outcomes (increased risk aversion after a previous win, ‘outcome history’).ResultsWhile the low MDQ group was risk averse after a win, this was less evident in the high MDQ group and least so in the patients with BD. Neurally, ‘outcome history’ was linked to medial frontal pole activation at the time of the decision. Corresponding to the behavioural effect, this activation was reduced in the high MDQ vs. the low MDQ group. While lithium did not reverse the pattern of BD in the task, it changed reward processing in the dorsolateral prefrontal cortex.DiscussionHealthy participants’ modulation of risk-taking in response to reward outcomes was reduced by risk of BD and BD. These results provide a model for how reward may prime escalation of risk-related behaviours in bipolar disorder and how mood stabilising treatments may work.