Biological Psychiatry Laboratory, McLean Hospital, Belmont, MA 02478, USA.
Neuropsychopharmacology. 2010 Feb;35(3):834-46. doi: 10.1038/npp.2009.191. Epub 2009 Dec 2.
Glutamatergic abnormalities may underlie bipolar disorder (BD). The glutamate-modulating drug riluzole may be efficacious in bipolar depression, but few in vivo studies have examined its effect on glutamatergic neurotransmission. We conducted an exploratory study of the effect of riluzole on brain glutamine/glutamate (Gln/Glu) ratios and levels of N-acetylaspartate (NAA). We administered open-label riluzole 100-200 mg daily for 6 weeks to 14 patients with bipolar depression and obtained imaging data from 8-cm(3) voxels in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) at baseline, day 2, and week 6 of treatment, using two-dimensional J-resolved proton magnetic resonance spectroscopy at 4 T. Imaging data were analyzed using the spectral-fitting package, LCModel; statistical analysis used random effects mixed models. Riluzole significantly reduced Hamilton Depression Rating Scale (HAM-D) scores (d=3.4; p<0.001). Gln/Glu ratios increased significantly by day 2 of riluzole treatment (Cohen's d=1.2; p=0.023). NAA levels increased significantly from baseline to week 6 (d=1.2; p=0.035). Reduction in HAM-D scores was positively associated with increases in NAA from baseline to week 6 in the ACC (d=1.4; p=0.053), but was negatively associated in the POC (d=9.6; p<0.001). Riluzole seems to rapidly increase Gln/Glu ratios-suggesting increased glutamate-glutamine cycling, which may subsequently enhance neuronal plasticity and reduce depressive symptoms. Further investigation of the Gln/Glu ratio as a possible early biomarker of response to glutamate-modulating therapies is warranted.
谷氨酸能异常可能是双相情感障碍（BD）的基础。谷氨酸调节药物利鲁唑可能对双相抑郁有效，但很少有体内研究检查其对谷氨酸能神经传递的影响。我们进行了一项探索性研究，研究利鲁唑对脑谷氨酰胺/谷氨酸（Gln/Glu）比值和 N-乙酰天冬氨酸（NAA）水平的影响。我们对 14 名双相抑郁患者给予利鲁唑 100-200mg 每日一次，共 6 周，并在基线、治疗第 2 天和第 6 周，使用 4T 上的二维 J 分辨质子磁共振波谱，从扣带前皮质（ACC）和顶枕叶皮质（POC）的 8cm(3)体素中获得成像数据。使用 LCModel 软件包对成像数据进行分析；使用随机效应混合模型进行统计分析。利鲁唑显著降低汉密尔顿抑郁评定量表（HAM-D）评分（d=3.4；p<0.001）。利鲁唑治疗第 2 天 Gln/Glu 比值显著升高（Cohen's d=1.2；p=0.023）。从基线到第 6 周，NAA 水平显著升高（d=1.2；p=0.035）。从基线到第 6 周，HAM-D 评分的降低与 ACC 中 NAA 的增加呈正相关（d=1.4；p=0.053），但与 POC 中 NAA 的增加呈负相关（d=9.6；p<0.001）。利鲁唑似乎能迅速增加 Gln/Glu 比值，提示谷氨酸-谷氨酰胺循环增加，这可能随后增强神经元可塑性并减轻抑郁症状。进一步研究 Gln/Glu 比值作为谷氨酸调节治疗反应的早期生物标志物是必要的。
