Brown E Sherwood, Wolfshohl Justin, Shad Mujeeb U, Vazquez Miguel, Osuji I Julian
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-8849, USA.
Neuropsychopharmacology. 2008 Sep;33(10):2376-83. doi: 10.1038/sj.npp.1301627. Epub 2007 Nov 14.
An extensive animal literature suggests that excessive corticosteroid exposure is associated with changes in memory and the hippocampus. Agents that decrease glutamate attenuate corticosteroid effects on the hippocampus. Minimal data are available on preventing or reversing corticosteroid effects on the human hippocampus. We previously reported that open-label lamotrigine was associated with significant improvement in declarative memory in corticosteroid-treated patients. We now examine the impact of 24 weeks of randomized, placebo-controlled lamotrigine therapy on declarative memory (primary aim) and hippocampal volume (secondary aim) in 28 patients (n=16 for lamotrigine, n=12 for placebo) taking prescription corticosteroids. All participants with data from at least one postbaseline assessment (n=9 for lamotrigine, n=11 for placebo) were included in the analysis. Declarative memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT) at baseline and weeks 12 and 24. Hippocampal and total brain volumes were manually traced from MRI scans obtained at baseline and week 24. On the basis of an ANCOVA analysis, total words learned on the RAVLT at exit were significantly greater in the lamotrigine group (n=8, missing data or dropouts n=8) compared to the placebo group (n=11, dropout n=1). RAVLT scores in the lamotrigine group increased from mildly impaired to average range. Hippocampal volume changes were small in both lamotrigine (n=7) and placebo (n=7) groups during the 24-week assessment period and between-group differences were not significant. Results suggest that lamotrigine may improve declarative memory in patients taking prescription corticosteroids although differential dropout rate in the two groups is a concern.
大量动物研究文献表明，皮质类固醇暴露过多与记忆及海马体变化有关。降低谷氨酸水平的药物可减轻皮质类固醇对海马体的影响。关于预防或逆转皮质类固醇对人类海马体影响的数据极少。我们之前报告过，开放标签的拉莫三嗪与接受皮质类固醇治疗患者的陈述性记忆显著改善有关。我们现在研究24周随机、安慰剂对照的拉莫三嗪治疗对28例服用处方皮质类固醇患者（拉莫三嗪组n = 16，安慰剂组n = 12）的陈述性记忆（主要目标）和海马体体积（次要目标）的影响。所有至少有一次基线后评估数据的参与者（拉莫三嗪组n = 9，安慰剂组n = 11）都纳入了分析。在基线、第12周和第24周用雷伊听觉词语学习测验（RAVLT）评估陈述性记忆。从基线和第24周获得的MRI扫描中手动描绘海马体和全脑体积。基于协方差分析，与安慰剂组（n = 11，退出1例）相比，拉莫三嗪组（n = 8，缺失数据或退出8例）在试验结束时RAVLT上学习的总单词数显著更多。拉莫三嗪组的RAVLT分数从轻度受损提高到平均范围。在24周评估期内，拉莫三嗪组（n = 7）和安慰剂组（n = 7）的海马体体积变化都很小，组间差异不显著。结果表明，拉莫三嗪可能改善服用处方皮质类固醇患者的陈述性记忆，尽管两组不同的退出率令人担忧。
