Silverstone Peter H, Asghar Sheila J, O'Donnell Tina, Ulrich Michele, Hanstock Christopher C
Department of Psychiatry, University of Alberta, 1E1.07 Mackenzie Center, 8440 - 112 Street, Edmonton AB, Canada.
World J Biol Psychiatry. 2004 Jan;5(1):38-44. doi: 10.1080/15622970410029906.
Lithium may affect brain choline concentrations, and this effect has been proposed to potentially explain its clinical efficacy. Since dextro-amphetamine is a useful human model of mania, we were interested in determining firstly whether dextro-amphetamine would alter brain choline concentrations, and secondly to determine if lithium would protect against any such changes in bipolar patients. In addition, we wanted to determine if valproate would also have any effects upon choline levels.
Healthy controls (n=18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking lithium (n=14) or valproate (n=11). We utilized (1)H-magnetic resonance spectroscopy ((1)H-MRS) in a 3.0T scanner to examine brain choline/phosphocholine+creatine (Cho/Cr) ratios. Changes in this ratio were measured to determine any changes in choline concentrations in the temporal lobe.
The results showed that administration of dextro-amphetamine decreased the Cho/Cr ratios. In contrast, in both the lithium-treated and valproate-treated patients this decrease was not seen; this attenuation in the change in Cho/Cr ratio changes was statistically significant. It should be noted that Cho/Cr ratios were significantly higher at baseline in the controls compared to both groups of patients, which may have influenced the results.
These findings are the first to examine the effects of dextro-amphetamine on brain choline concentrations. They show that while in controls dextro-amphetamine decreases choline concentrations, lithium and valproate both appear to protect against this effect in bipolar patients. However, as brain ratios were measured rather than the absolute concentration of choline, and these ratios were lowered in patients at baseline, these results must be regarded as preliminary and require replication in future studies.
锂可能会影响大脑胆碱浓度，有人提出这种影响可能解释其临床疗效。由于右旋苯丙胺是一种有用的人类躁狂症模型，我们首先感兴趣的是确定右旋苯丙胺是否会改变大脑胆碱浓度，其次是确定锂是否能预防双相情感障碍患者出现的此类变化。此外，我们想确定丙戊酸盐是否也会对胆碱水平产生影响。
将健康对照组（n = 18）与服用锂盐（n = 14）或丙戊酸盐（n = 11）的双相情感障碍I型和II型缓解期患者进行比较。我们在3.0T扫描仪中利用氢磁共振波谱（1H-MRS）检查大脑胆碱/磷酸胆碱+肌酸（Cho/Cr）比值。测量该比值的变化以确定颞叶胆碱浓度的任何变化。
结果显示，服用右旋苯丙胺会降低Cho/Cr比值。相比之下，在服用锂盐和丙戊酸盐的患者中均未观察到这种降低；Cho/Cr比值变化的这种减弱具有统计学意义。需要注意的是，与两组患者相比，对照组的基线Cho/Cr比值显著更高，这可能影响了结果。
这些发现首次研究了右旋苯丙胺对大脑胆碱浓度的影响。结果表明，在对照组中右旋苯丙胺会降低胆碱浓度，而锂盐和丙戊酸盐似乎都能预防双相情感障碍患者出现这种效应。然而，由于测量的是大脑比值而非胆碱的绝对浓度，且患者的基线比值较低，这些结果必须被视为初步结果，需要在未来的研究中进行重复验证。
