Bertolino A, Callicott J H, Elman I, Mattay V S, Tedeschi G, Frank J A, Breier A, Weinberger D R
Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Neurosciences Center at Saint Elizabeths, Washington, DC 20032, USA.
Biol Psychiatry. 1998 May 1;43(9):641-8. doi: 10.1016/s0006-3223(97)00555-6.
Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of the present study was twofold: to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients.
We studied 12 medication-free patients, 5 of whom were "drug naive" and symptomatic for a mean of 12 years, and 12 control subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE] for multiple cortical and subcortical regions. Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data.
Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios, length of illness, and volumes of the hippocampal region and frontal lobe. Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications.
Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated.
质子磁共振波谱成像（1H-MRSI）研究报告称，在接受药物治疗的精神分裂症患者的海马区（HIPPO）和背外侧前额叶皮质（DLPFC）中，作为神经元完整性标志物的N-乙酰天门冬氨酸（NAA）有所减少。本研究的目的有两个：排除药物治疗作为先前研究结果的一个来源，并检查一组未经治疗的慢性患者样本中NAA的相对浓度。
我们研究了12名未服药的患者，其中5名是“初治患者”，平均患病12年，以及12名对照受试者。测定了多个皮质和皮质下区域质子谱代谢物峰下面积的比值[即NAA/肌酸（CRE）、NAA/胆碱（CHO）、CHO/CRE]。还测量了海马结构和额叶体积，以测试其与1H-MRSI数据的相关性。
在双侧海马区和背外侧前额叶皮质中发现NAA/CRE和NAA/CHO显著降低。在任何其他采样区域，CHO/CRE或NAA比值均无显著变化。代谢物比值、病程长度与海马区和额叶体积之间未发现显著相关性。与亚急性患者和先前研究的接受药物治疗的慢性患者相比，慢性患病但仍未服药的患者的平均比值和效应大小没有差异。
海马区和背外侧前额叶皮质中NAA比值的双侧降低是可靠的发现。这些发现提示了一种相对局限的神经化学病理模式，无论是否用药，这种模式似乎都不会随着病程延长而改变。
