Cognition and dorsolateral prefrontal cortex volume in corticosteroid- treated patients given lamotrigine

In addition to changes in declarative memory and the hippocampus, corticosteroid excess is associated with prefrontal cortex changes. We previously reported that patients receiving exogenous corticosteroid therapy had impaired performance on prefrontal cortex-related tasks, including working memory and executive functioning tasks. Glutamate release inhibitors attenuate corticosteroid-effects on the hippocampus in both animal and human models. Twenty-eight outpatients receiving chronic prednisone therapy for transplant rejection or other medical conditions were randomized to lamotrigine (a glutamate release inhibitor) or placebo for 24 weeks. Dorsolateral prefrontal cortex (DLPFC) volume was manually traced from MRI scans by trained staff members. Cognition was examined using the Stroop Color Word Test (SCWT), Delis-Kaplan Executive Function System (D-KEFS) and the Trail Making Test. Groups were compared using analysis of covariance. Consistent with prior findings in corticosteroid-treated patients, baseline cognitive function was in the low normal range. At baseline, prednisone duration showed a trend towards negative correlation with SCWT and D-KEFS inhibition switching time error scores, and DLPFC volume showed a trend towards a positive correlation with SCWT scores. No significant between-group differences in outcomes were observed following lamotrigine therapy. Thus, this study found lamotrigine to not be associated with either positive or negative effects on cognition or DLPFC volume.