Bipolar Disorder (BD) is associated with impairment in emotional self-regulation and verbal working memory. Lamotrigine (LTG) is effective in the clinical management of BD.

To investigate whether treatment with LTG is coupled with altered function within neural circuits subserving emotional processing and verbal working memory, in a BDI sample.

Functional Magnetic Resonance Imaging (MRI) was used to explore blood oxygenation level-dependent (BOLD) response across the whole brain in 12 stable BDI patients at baseline and following 12 weeks of LGT monotherapy. Stimuli were presented in a block-design while individuals performed a verbal working memory (N-back sequential letter) task and in an event-related fashion during an angry facial affect recognition task. Data was acquired using a 1.5-Tesla MRI scanner and analysed using SPM2. Group activation maps were generated for each task and for the drug-free and post-medication condition. A threshold of p < 0.001 was used. Effect of LGT on brain activation during tasks was explored using a random-effects, within-group comparison.

In both tasks, LGT monotherapy was associated with increased BOLD signal when compared to baseline in a number of brain regions, mostly within the prefrontal cortex and cingulate gyrus. All foci of increased activation with LTG monotherapy were observed within cortical regions normally engaged in verbal working memory and facial affect processing.

LTG monotherapy in BD patients may enhance cortical function within neural circuits involved in memory and emotional self-regulation.

This study was supported by an unrestricted GlaxoSmithKline grant.