Brown E Sherwood, Jeon-Slaughter Haekyung, Lu Hanzhang, Jamadar Rhoda, Issac Sruthy, Shad Mujeeb, Denniston Daren, Tamminga Carol, Nakamura Alyson, Thomas Binu P
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
The Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Neuropsychopharmacology. 2015 Mar 13;40(5):1216-21. doi: 10.1038/npp.2014.307.
In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=-0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids.
在动物模型中，皮质酮水平升高与海马体变化相关，而苯妥英可以预防这些变化。在人类中，库欣综合征和长期使用处方皮质类固醇与海马体体积减小有关。然而，关于短期给予皮质类固醇对海马体的影响，人们知之甚少。本报告研究了短期氢化可的松暴露期间海马体体积的变化，以及体积变化是否能被苯妥英阻断。对17名健康成年人进行了一项随机、双盲、安慰剂对照的受试者内交叉研究。参与者接受氢化可的松（160毫克/天）/安慰剂、苯妥英/安慰剂、两种药物联合使用或安慰剂/安慰剂，每种用药情况之间有21天的洗脱期。在每种用药情况后进行结构磁共振成像扫描并检测皮质醇水平。氢化可的松对全脑体积无显著影响。然而，与安慰剂相比，氢化可的松使海马体总体积显著减少了1.69%。苯妥英阻断了与氢化可的松相关的体积减小。海马体体积的减小与皮质醇水平的变化相关（r=-0.58，P=0.03）。据我们所知，这是首次报道短期暴露于皮质类固醇后海马体结构的变化。海马体体积变化与皮质醇水平之间的相关性表明，体积变化与皮质醇升高有关。尽管这项初步研究的结果需要重复验证，但它们表明，即使在短期暴露于皮质类固醇期间，海马体体积也会减小，并且与动物模型一样，海马体的变化可以被苯妥英阻断。这些结果可能对理解海马体对应激的反应以及接受处方皮质类固醇治疗的患者都有意义。
