Chang Linda, Friedman Joseph, Ernst Thomas, Zhong Kai, Tsopelas Nicholas D, Davis Kenneth
Department of Medicine, John A. Burns School of Medicine, Honolulu, Hawaii 96813, USA.
Biol Psychiatry. 2007 Dec 15;62(12):1396-404. doi: 10.1016/j.biopsych.2007.05.025. Epub 2007 Aug 13.
Abnormalities in the white matter of the brain may occur in individuals with schizophrenia as well as with normal aging. Therefore, elderly schizophrenic patients may suffer further cognitive decline as they age. This study determined whether elderly schizophrenia participants, especially those with declined cognitive function (Clinical Dementia Rating score > 1), show white matter metabolite abnormalities on proton magnetic resonance spectroscopy and whether there are group differences in age-dependent changes in these brain metabolites.
Twenty-three elderly schizophrenia and twenty-two comparison participants fulfilling study criteria were enrolled. Localized, short echo-time (1)H MRS at 4 Tesla was used to assess neurometabolite concentrations in several white matter regions.
Compared with healthy subjects, schizophrenia participants had lower N-acetyl compounds (-12.6%, p = .0008), lower myo-inositol (-16.4%, p = .026), and higher glutamate + glutamine (+28.7%, p = .0016) concentrations across brain regions. Schizophrenia participants with Clinical Dementia Rating >/= 1 showed the lowest NA in the frontal and temporal regions compared with control subjects. Interactions between age and schizophrenia status on total creatine and choline-containing compounds were observed; only schizophrenia participants showed age-related decreases of these metabolites in the right frontal region.
Decreased NA in these white matter brain regions likely reflects reduced neuronal content associated with decreased synapses and neuronal cell volumes. The elevated glutamate + glutamine, if reflecting elevated glutamate, could result from excess neuronal glutamate release or glial dysfunction in glutamate reuptake. The decreased myo-inositol in participants with schizophrenia suggests decreased glial content or dysfunctional glia, which might result from glutamate-mediated toxicity.
大脑白质异常可能发生在精神分裂症患者以及正常衰老的个体中。因此，老年精神分裂症患者随着年龄增长可能会出现进一步的认知衰退。本研究旨在确定老年精神分裂症参与者，尤其是那些认知功能下降（临床痴呆评定量表评分>1）的患者，在质子磁共振波谱上是否存在白质代谢物异常，以及这些脑代谢物的年龄依赖性变化是否存在组间差异。
招募了23名符合研究标准的老年精神分裂症患者和22名对照参与者。使用4特斯拉的局部、短回波时间（1）H MRS来评估几个白质区域的神经代谢物浓度。
与健康受试者相比，精神分裂症参与者在全脑区域的N-乙酰化合物浓度较低（-12.6%，p = 0.0008），肌醇浓度较低（-16.4%，p = 0.026），谷氨酸+谷氨酰胺浓度较高（+28.7%，p = 0.0016）。临床痴呆评定量表评分≥1的精神分裂症参与者与对照受试者相比，额叶和颞叶区域的N-乙酰化合物浓度最低。观察到年龄与精神分裂症状态对总肌酸和含胆碱化合物的交互作用；只有精神分裂症参与者在右侧额叶区域出现了这些代谢物与年龄相关的下降。
这些白质脑区中N-乙酰化合物浓度降低可能反映了与突触和神经元细胞体积减少相关的神经元含量减少。谷氨酸+谷氨酰胺浓度升高，如果反映谷氨酸升高，可能是由于神经元谷氨酸释放过多或谷氨酸再摄取中的胶质细胞功能障碍所致。精神分裂症参与者中肌醇减少表明胶质细胞含量减少或胶质细胞功能障碍，这可能是由谷氨酸介导的毒性引起的。
