Regional Decoupling of N-acetyl-aspartate and Glutamate in Schizophrenia
Regional Decoupling of N-acetyl-aspartate and Glutamate in Schizophrenia
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DOI：
10.1038/npp.2012.126
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发表时间：
2012-11-01
影响因子：
7.6
通讯作者：
Lahti, Adrienne C.
中科院分区：
文献类型：
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作者：
Kraguljac, Nina V.;Reid, Meredith A.;Lahti, Adrienne C.
质子磁共振波谱(H-1-MRS)可以无创地测量几种代谢物，包括N-乙酰天冬氨酸(NAA)和谷氨酸(Glamate)，N-乙酰天冬氨酸(NAA)是一种专门在神经元线粒体中合成的氨基酸，谷氨酸是参与兴奋性神经传递和代谢的氨基酸。鉴于最近对精神分裂症(SZ)的尸检研究揭示了线粒体异常以及调节谷氨酸-谷氨酰胺循环的酶的扰动表达，我们假设SZ存在NAA和谷氨酸动态平衡的破坏。50名SZ患者和48名健康对照(HC)参加了这项H-1-MRS研究。在前扣带回皮质(ACC)和海马区放置体素，获得NAA/Cr和谷氨酸+谷氨酰胺(GLX)/Cr比值。我们没有发现两组之间在ACC和海马区的代谢物水平上有任何显著的差异。在海马区，Hc组NAA/Cr和Glx/Cr值显著相关(r=0.4，p<；0.01(校正p=0.048))，而SZ组无显著相关(r=-0.06；p=0.71)，差异有统计学意义(z=2.22，p=0.02)。尽管SZ和HC的神经代谢产物无明显差异，但健康受试者海马区NAA/Cr值与Glx/Cr值存在相关性，而SZ受试者则失去了这种相关性。据我们所知，这是第一项表明这些代谢物脱偶的研究，这可能是SZ独有的病理生理变化。然而，在得出确定的结论之前，这些结果值得复制和进一步探索。神经精神药理学(2012年)37,2635-2642；DOI：10.1038/npp.2012.126；2012年7月18日在线发布
Proton magnetic resonance spectroscopy (H-1-MRS) allows the non-invasive measurement of several metabolites, including N-acetylaspartate (NAA), an amino acid exclusively synthesized in the mitochondria of neurons, and glutamate, an amino acid involved in excitatory neurotransmission and metabolism. In view of recent postmortem studies in schizophrenia (SZ) revealing mitochondrial abnormalities as well as perturbed expression of the enzymes regulating the glutamate-glutamine cycle, we hypothesized that a disruption in the homeostasis of NAA and glutamate in SZ is present. Fifty subjects with SZ and 48 matched healthy controls (HC) were enrolled in this H-1-MRS study. Voxels were placed in the anterior cingulate cortex (ACC) and hippocampus; NAA/Cr and glutamate + glutamine (Glx)/Cr ratios were obtained. We did not find any significant differences between the groups in metabolite levels in both the ACC and hippocampus. In the hippocampus we found that NAA/Cr and Glx/Cr ratios were significantly correlated in HC (r = 0.40, p < 0.01 (corrected p = 0.048)) but not in SZ (r = -0.06; p = 0.71), a difference that was statistically significant (z = 2.22, p = 0.02). Although no differences in neurometabolites between SZ and HC were apparent, correlations between NAA/Cr and Glx/Cr in healthy subjects in the hippocampus were found, and this correlation was lost in subjects with SZ. To our knowledge, this is the first study to suggest decoupling of these metabolites, a pathophysiological change that may be unique to SZ. However, these results warrant replication and further exploration before definite conclusions can be drawn. Neuropsychopharmacology (2012) 37, 2635-2642; doi:10.1038/npp.2012.126; published online 18 July 2012