Silverstone Peter H, Wu Ren H, O'Donnell Tina, Ulrich Michele, Asghar Sheila J, Hanstock Christopher C
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Int Clin Psychopharmacol. 2003 Mar;18(2):73-9. doi: 10.1097/00004850-200303000-00002.
Previous studies have found that treatment with lithium over a 4-week period may increase the concentration of N-acetyl-aspartate (NAA) in both bipolar patients and controls. In view of other findings indicating that NAA concentrations may be a good marker for neuronal viability and/or functioning, it has been further suggested that some of the long term benefits of lithium may therefore be due to actions to improve these neuronal properties. The aim of the present study was to utilize H magnetic resonance spectroscopy ( H MRS) to further examine the effects of both lithium and sodium valproate upon NAA concentrations in treated euthymic bipolar patients. In the first part of the study, healthy controls (n =18) were compared with euthymic bipolar patients (type I and type II) who were taking either lithium (n =14) or sodium valproate (n =11), and NAA : creatine ratios were determined. In the second part, we examined a separate group of euthymic bipolar disorder patients taking sodium valproate (n =9) and compared these to age- and sex-matched healthy controls (n =11), and we quantified the exact concentrations of NAA using an external solution. The results from the first part of the study showed that bipolar patients chronically treated with lithium had a significant increase in NAA concentrations but, in contrast, there were no significant increases in the sodium valproate-treated patients compared to controls. The second part of the study also found no effects of sodium valproate on NAA concentrations. These findings are the first to compare NAA concentrations in euthymic bipolar patients being treated with lithium or sodium valproate. The results support suggestions that longer-term administration of lithium to bipolar patients may increase NAA concentrations. However, the study suggests that chronic administration of sodium valproate to patients does not lead to similar changes in NAA concentrations. These findings suggest that sodium valproate and lithium may not share a common mechanism of action in bipolar disorder involving neurotrophic or neuroprotective effects.
以往的研究发现，在4周的时间内使用锂进行治疗，可能会使双相情感障碍患者和对照组的N-乙酰天门冬氨酸（NAA）浓度升高。鉴于其他研究结果表明，NAA浓度可能是神经元活力和/或功能的良好标志物，因此进一步有人提出，锂的一些长期益处可能归因于其改善这些神经元特性的作用。本研究的目的是利用氢磁共振波谱（1H MRS）进一步研究锂和丙戊酸钠对处于缓解期的双相情感障碍患者NAA浓度的影响。在研究的第一部分，将健康对照组（n = 18）与正在服用锂盐（n = 14）或丙戊酸钠（n = 11）的处于缓解期的双相I型和II型情感障碍患者进行比较，并测定NAA与肌酸的比率。在第二部分中，我们研究了另一组服用丙戊酸钠的处于缓解期的双相情感障碍患者（n = 9），并将他们与年龄和性别匹配的健康对照组（n = 11）进行比较，我们使用外部溶液对NAA的精确浓度进行了量化。研究第一部分的结果表明，长期接受锂治疗的双相情感障碍患者的NAA浓度显著升高，但相比之下，与对照组相比，丙戊酸钠治疗的患者NAA浓度没有显著升高。研究的第二部分也发现丙戊酸钠对NAA浓度没有影响。这些发现首次比较了接受锂或丙戊酸钠治疗的处于缓解期的双相情感障碍患者的NAA浓度。结果支持了对双相情感障碍患者长期服用锂可能会增加NAA浓度的建议。然而，该研究表明，对患者长期服用丙戊酸钠不会导致NAA浓度发生类似变化。这些发现表明，丙戊酸钠和锂在双相情感障碍中可能不存在涉及神经营养或神经保护作用的共同作用机制。
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