Effects of lamotrigine on hippocampal activation in corticosteroid-treated patients

Background: An extensive animal literature suggests that stress or excessive corticosteroid exposure is associated with changes in hippocampal function and memory. These findings are pertinent to psychiatric disorders with elevated cortisol, Cushing's disease and the millions of patients receiving prescription corticosteroids. In animals, agents that decrease glutamate release attenuate the effects of corticosteroids on the hippocampus. Minimal data are available on preventing or reversing the effects of corticosteroids on the human hippocampus. We previously reported improvement in memory in corticosteroid-treated patients given lamotrigine. In this report, we examined the impact of lamotrigine on task-related hippocampal activation in patients taking prescription corticosteroids. Methods: A total of 28 outpatients taking long-term oral prednisone for medical conditions, such as renal transplant rejection, were randomized to lamotrigine or placebo for 24 weeks. Hippocampal activation in response to a visual memory task was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). Results: Consistent with a reduction in glutamate release, the right posterior hippocampus showed a significant decrease in task-related activation in the lamotrigine group as compared to the placebo group. Limitations: The modest sample size and an assessment period of only 24 weeks are study limitations. Conclusions: Between-group differences in hippocampal activation were observed. The results suggest that an agent that modulates glutamate may modify the effects of long-term corticosteroid exposure on the human hippocampus.