Frye Mark A, Tsai Guochuan E, Huggins Teresa, Coyle Joseph T, Post Robert M
Department of Psychiatry, University of California Los Angeles Neuropsychiatric Institute, Los Angeles, CA, USA.
Biol Psychiatry. 2007 Jan 15;61(2):162-6. doi: 10.1016/j.biopsych.2006.01.024. Epub 2006 Jun 2.
Glutamatergic dysregulation has been documented in schizophrenia but has received less systematic study in affective illness.
Cerebrospinal fluid (CSF) levels of the excitatory amino acids glutamate (Glu) and aspartate (Asp) and the N-methyl-D-aspartate (NMDA) receptor modulator, glycine (GLY) were measured by high performance liquid chromatography in 32 patients with refractory affective disorder (16 female/16 male, 12 bipolar I, 12 bipolar II, and 8 unipolar) and in 14 age-matched controls.
There was a significant reduction in CSF glutamate and glycine in patients versus controls. A diagnosis by sex interaction was present for CSF glycine with lower levels in female patients compared to female controls. Levels of the excitatory amino acids were highly inter-correlated in patients, but not in controls. In patients studied after 6 weeks of lamotrigine, there was a trend for CSF glutamate levels to increase.
These data suggest that in patients with refractory affective disorder, excitatory amino acids are dysregulated, as exemplified both by the decreased CSF glutamate and glycine and their high intercorrelation compared to controls. Further controlled study of glutamatergic dysregulation and its relationship to the pathophysiology of affective disorders and potential mechanism of action of mood stabilizers appears indicated.
谷氨酸能调节异常在精神分裂症中已有记录，但在情感性疾病中较少受到系统研究。
采用高效液相色谱法测定了32例难治性情感障碍患者（16例女性/16例男性，12例双相I型，12例双相II型，8例单相）和14例年龄匹配对照者脑脊液（CSF）中兴奋性氨基酸谷氨酸（Glu）、天冬氨酸（Asp）以及N-甲基-D-天冬氨酸（NMDA）受体调节剂甘氨酸（GLY）的水平。
与对照组相比，患者脑脊液中的谷氨酸和甘氨酸显著降低。脑脊液甘氨酸存在性别交互作用诊断，女性患者水平低于女性对照。兴奋性氨基酸水平在患者中高度相互关联，但在对照组中并非如此。在接受拉莫三嗪治疗6周后的患者中，脑脊液谷氨酸水平有升高趋势。
这些数据表明，在难治性情感障碍患者中，兴奋性氨基酸调节异常，脑脊液谷氨酸和甘氨酸降低以及与对照组相比它们之间的高度相互关联即为例证。似乎需要对谷氨酸能调节异常及其与情感障碍病理生理学的关系以及心境稳定剂的潜在作用机制进行进一步的对照研究。
