Abbott Christopher, Bustillo Juan
Departments of Psychiatry and Neuroscience, University of New Mexico, Albuquerque, New Mexico 87131, USA.
Curr Opin Psychiatry. 2006 Mar;19(2):135-9. doi: 10.1097/01.yco.0000214337.29378.cd.
This review discusses recent studies investigating schizophrenia with proton magnetic resonance spectroscopy including the first meta-analysis [Steen RG, Hamer RM, Lieberman JA. Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychology 2005; 30:1949-1962]. We also highlight methodological issues and suggest a modality for future research to further explore glutamatergic dysfunction in schizophrenia.
Despite methodological differences, spectroscopy studies with schizophrenia show reductions in N-acetylaspartate in the medial temporal and prefrontal regions. Other areas such as the anterior cingulate, parietal cortex thalamus, and cerebellum may also have N-acetylaspartate reductions. The proton magnetic resonance spectroscopy studies at higher fields and with shorter echo time have revealed abnormalities in glutamate and glutamine. Animal studies have shown that the discrepancies in metabolites between patients and controls are not due to antipsychotic medication exposure, and that chronic exposure to N-methyl-D-aspartate antagonists has produced decreased N-acetylaspartate in the temporal cortex. The human and animal studies both support an excitoxic glutamatergically mediated process that may explain decreased N-acetylaspartate, volume loss, and the poor outcomes of schizophrenia.
Use of higher field strengths and longitudinal studies may reveal a progressive excitoxic glutamatergic process that leads to N-acetylaspartate and volume reductions. This may lead to the development of neuroprotective agents that change the course of schizophrenia.
本综述讨论了近期利用质子磁共振波谱研究精神分裂症的相关研究，包括首个荟萃分析[Steen RG, Hamer RM, Lieberman JA. 精神分裂症患者脑代谢物的1H磁共振波谱测量：系统综述与荟萃分析。神经心理学2005; 30:1949 - 1962]。我们还强调了方法学问题，并提出了未来研究的一种模式，以进一步探索精神分裂症中的谷氨酸能功能障碍。
尽管存在方法学差异，但针对精神分裂症的波谱研究显示，内侧颞叶和前额叶区域的N - 乙酰天门冬氨酸减少。其他区域，如前扣带回、顶叶皮质、丘脑和小脑，N - 乙酰天门冬氨酸也可能减少。更高场强和更短回波时间的质子磁共振波谱研究揭示了谷氨酸和谷氨酰胺的异常。动物研究表明，患者与对照组之间代谢物的差异并非由于抗精神病药物暴露所致，且长期暴露于N - 甲基 - D - 天门冬氨酸拮抗剂会导致颞叶皮质N - 乙酰天门冬氨酸减少。人体和动物研究均支持一种兴奋性毒性的谷氨酸能介导过程，这可能解释了N - 乙酰天门冬氨酸减少、体积缩小以及精神分裂症的不良预后。
使用更高场强和纵向研究可能会揭示一个渐进性的兴奋性毒性谷氨酸能过程，该过程导致N - 乙酰天门冬氨酸和体积减少。这可能会促使开发出改变精神分裂症病程的神经保护剂。
