Bustillo Juan R, Rowland Laura M, Jung Rex, Brooks William M, Qualls Clifford, Hammond Roger, Hart Blaine, Lauriello John
Department of Psychiatry, University of New Mexico, Albuquerque, NM 87131-0001, USA.
Neuropsychopharmacology. 2008 Sep;33(10):2456-66. doi: 10.1038/sj.npp.1301631. Epub 2007 Dec 19.
Reduced brain N-acetyl-aspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. We studied 32 minimally treated schizophrenia patients and 21 healthy subjects with single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) of the frontal and occipital lobes, caudate nucleus, and cerebellum. Concentrations of NAA, Choline, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind manner with either haloperidol or quetiapine. (1)H-MRS was repeated every 6 months for up to 2 years. There was a group main effect for baseline NAA with lower global NAA in schizophrenia subjects before treatment compared to healthy controls. Global NAA was directly related to measures of global cognitive performance in the whole subject sample. Following treatment with haloperidol or quetiapine, there were no changes in NAA in any of the regions studied. Early in the illness, schizophrenia patients already demonstrate subtle reductions in NAA. Treatment with typical or atypical antipsychotic medications for several months does not result in NAA changes.
慢性精神分裂症患者大脑中的N-乙酰天门冬氨酸（NAA）含量反复被发现有所降低，这表明存在神经元丢失或功能障碍。然而，抗精神病药物对NAA的潜在混杂效应尚未得到解决。我们对32例接受最少治疗的精神分裂症患者和21名健康受试者进行了研究，采用单体素质子磁共振波谱（(1)H-MRS）对额叶、枕叶、尾状核和小脑进行检测。测定了NAA、胆碱和肌酸的浓度，并根据体素中脑脊液（CSF）的比例进行了校正。患者以随机对照双盲方式接受氟哌啶醇或喹硫平治疗。每6个月重复进行(1)H-MRS检测，持续2年。在基线时，精神分裂症患者的整体NAA水平低于健康对照组，存在组间主效应。在整个受试者样本中，整体NAA与整体认知表现指标直接相关。在接受氟哌啶醇或喹硫平治疗后，所研究的任何区域的NAA均无变化。在疾病早期，精神分裂症患者的NAA就已出现细微降低。使用典型或非典型抗精神病药物治疗数月不会导致NAA发生变化。
