Brown E Sherwood, Beard Laura, Frol Alan B, Rush A John
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-8849, USA.
Neurobiol Learn Mem. 2006 Jul;86(1):28-34. doi: 10.1016/j.nlm.2005.12.009. Epub 2006 Feb 3.
Corticosteroids are essential for life and an integral part of the stress response. However, in excess, corticosteroids can be associated with a variety of effects on the brain including hippocampal atrophy and even neuronal death, mood changes, and declarative memory impairment. The magnitude of mood change in patients receiving prednisone is reportedly associated with previous lifetime corticosteroid exposure, consistent with a sensitization or kindling process whereby greater effects are observed with repeated exposure. To our knowledge, the effect of multiple corticosteroid exposures on mood and memory has not been previously examined prospectively in animals or humans. In this study, 30 human volunteers, with no history of systemic prescription corticosteroid therapy, were given (in random order using a crossover design) two 3-day exposures of prednisone (60 mg/day) and one of identical placebo, with 11-day washouts between each medication exposure. Before and after each 3-day prednisone/placebo exposure, declarative memory was assessed using different versions of the Rey Auditory Verbal Learning Test (RAVLT) to minimize practice or learning effects, while mood was assessed with the 21-item Hamilton Rating Scale for Depression, Young Mania Rating Scale and Internal State Scale. No significant mood changes were found. However, a significant decrease in aspects of RAVLT performance was observed after the first prednisone exposure consistent with a decline in declarative memory performance. The decline in RAVLT performance was significantly smaller after the second prednisone exposure as compared to the initial prednisone exposure. Thus, a second prednisone exposure was associated with an attenuated prednisone-effect on declarative memory. These data suggest tolerance or habituation, rather than sensitization, to prednisone effects on declarative memory during a second exposure. Implications and possible explanations for the findings are discussed.
皮质类固醇对生命至关重要，是应激反应不可或缺的一部分。然而，过量的皮质类固醇可能会对大脑产生多种影响，包括海马萎缩甚至神经元死亡、情绪变化和陈述性记忆损害。据报道，接受泼尼松治疗的患者情绪变化的程度与既往一生的皮质类固醇暴露有关，这与一种致敏或点燃过程一致，即反复暴露会观察到更大的影响。据我们所知，此前尚未在动物或人类中对多次皮质类固醇暴露对情绪和记忆的影响进行前瞻性研究。在本研究中，30名无全身性处方皮质类固醇治疗史的人类志愿者（采用交叉设计随机排序）接受了两次为期3天的泼尼松（60毫克/天）暴露和一次相同安慰剂暴露，每次药物暴露之间有11天的洗脱期。在每次为期3天的泼尼松/安慰剂暴露前后，使用不同版本的雷伊听觉词语学习测试（RAVLT）评估陈述性记忆，以尽量减少练习或学习效应，同时使用21项汉密尔顿抑郁评定量表、青年躁狂评定量表和内部状态量表评估情绪。未发现显著的情绪变化。然而，在首次泼尼松暴露后，观察到RAVLT表现的多个方面显著下降，这与陈述性记忆表现的下降一致。与首次泼尼松暴露相比，第二次泼尼松暴露后RAVLT表现的下降显著更小。因此，第二次泼尼松暴露与泼尼松对陈述性记忆的作用减弱有关。这些数据表明，在第二次暴露期间，对泼尼松对陈述性记忆的作用产生了耐受或习惯化，而不是致敏。本文讨论了这些发现的意义和可能的解释。
