Differential effects of chronic lithium and valproate on brain activation in healthy volunteers

Rationale Previous functional imaging studies have shown altered brain activity during cognitive task performance in bipolar patients. However, the fact that these patients are often on medication makes it unclear to what extent these changes reflect treatment effects. Objectives This study aims to identify regional brain activity changes occurring following lithium and valproate treatment in healthy volunteers. Methods This was a double‐blind, placebo‐controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9), or placebo (n = 12). Functional images were acquired using functional magnetic resonance imaging (fMRI) while subjects performed three cognitive tasks, a word generation paradigm, a spatial attention task and a working memory task. fMRI was carried out both before and after 14 days of treatment with valproate, lithium or placebo. The changes in the magnitude of the blood‐oxygen‐level‐dependent (BOLD) signal after treatment were compared between the groups using a one‐way ANOVA for each task followed by a post‐hoc multiple comparisons correction. Results A significant group effect was noted in the change in BOLD signal magnitude from baseline to post‐treatment, in all three tasks (working memory p