Department of Psychiatry, Dalhousie University, Halifax, NS.
J Psychiatry Neurosci. 2012 May;37(3):185-92. doi: 10.1503/jpn.110097.
Neuroprotective effects of lithium (Li) have been well documented in tissue cultures and animal models, whereas human data continue to be limited. Previous studies investigating the association between Li treatment and brain N-acetylaspartate (NAA), a putative neuronal marker, showed mixed results because of methodological heterogeneity.
To investigate the effects of Li on prefrontal cortex NAA levels, we compared patients with bipolar disorder from specialized Li clinics in Berlin and Halifax with at least 2 years of ongoing Li treatment (Li group), patients with lifetime Li exposure of less than 3 months more than 2 years ago (non-Li group) and healthy controls. Participants in both patient groups had at least 10 years of illness and 5 episodes. We measured left prefrontal NAA levels using 1.5-T magnetic resonance spectroscopy.
We enrolled 27 participants in the Li, 16 in the non-Li and 21 in the healthy control groups. The non-Li group had lower prefrontal NAA levels than the Li group (t41 = -3.44, corrected p < 0.01) or control participants (t35 = -2.91, corrected p < 0.05), who did not differ from the Li group (t46 = -0.14, p = 0.89). The same pattern of prefrontal NAA differences was replicated in both sites. In addition, there was a negative correlation between prefrontal NAA and duration of illness in the non-Li group (r = -0.60, p = 0.019) but not in the Li group (r = 0.07, p = 0.74).
Study limitations include the crosssectional design and exposure to other medications.
Whereas patients with bipolar disorder, substantial illness burden and limited lifetime Li exposure had significantly lower prefrontal NAA levels than controls, Li-treated patients with similar illness burden showed prefrontal NAA levels comparable to those of healthy controls. These findings provide indirect support for neuroprotective effects of Li and for negative effects of illness burden on prefrontal NAA levels in patients with bipolar disorder.
锂（Li）的神经保护作用在组织培养和动物模型中得到了充分证实，而人类数据仍然有限。先前的研究调查了 Li 治疗与脑 N-乙酰天冬氨酸（NAA）之间的关联，NAA 是一种假定的神经元标志物，但由于方法学的异质性，研究结果喜忧参半。
为了研究 Li 对前额叶皮层 NAA 水平的影响，我们比较了来自柏林和哈利法克斯专门 Li 诊所的有双相障碍的患者，这些患者接受了至少 2 年的 Li 治疗（Li 组），以及一生中 Li 暴露少于 3 个月但超过 2 年的患者（非 Li 组）和健康对照组。两组患者均至少有 10 年的病史和 5 次发作。我们使用 1.5-T 磁共振波谱测量左侧前额叶 NAA 水平。
我们纳入了 27 名 Li 组、16 名非 Li 组和 21 名健康对照组的参与者。非 Li 组的前额叶 NAA 水平低于 Li 组（t41 = -3.44，校正后 p < 0.01）或健康对照组（t35 = -2.91，校正后 p < 0.05），但 Li 组与非 Li 组之间无差异（t46 = -0.14，p = 0.89）。这一前额叶 NAA 差异模式在两个地点均得到了复制。此外，非 Li 组的前额叶 NAA 与病程呈负相关（r = -0.60，p = 0.019），但 Li 组无此相关性（r = 0.07，p = 0.74）。
研究的局限性包括横断面设计和暴露于其他药物。
与具有相似疾病负担的健康对照组相比，有双相障碍、疾病负担较重且 Li 暴露时间有限的患者的前额叶 NAA 水平明显较低，而 Li 治疗的患者则表现出类似的前额叶 NAA 水平。这些发现为 Li 的神经保护作用以及双相障碍患者的疾病负担对前额叶 NAA 水平的负面影响提供了间接支持。
