Chiappelli J, Hong L E, Wijtenburg S A, Du X, Gaston F, Kochunov P, Rowland L M
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Transl Psychiatry. 2015 Apr 14;5(4):e548. doi: 10.1038/tp.2015.43.
We investigated in vivo neurochemical markers reflective of neuronal health and glial activation to determine if these could yield clues regarding the reduced fractional anisotropy (FA) of white matter and accelerated decline of FA with age in schizophrenia. Participants with schizophrenia and healthy controls completed diffusion tensor imaging to assess FA and proton magnetic resonance spectroscopy to assess neurochemical metabolites in the same frontal region. Frontal FA was significantly lower in the schizophrenia and declined more rapidly with age compared with the healthy control group. In both groups, N-acetylaspartate (NAA), a putative marker of neuronal integrity, and glutamate declined with age, and this decline was stronger in patients. Myo-inositol, a marker of glial cells, was negatively related to FA in both groups. The relationship between FA and age remained significant in schizophrenia even when controlling for all metabolites. The relationships of FA, NAA and myo-inositol to age appear to be independent of one another. The relationship between FA and myo-inositol was independently present in both patients and controls, even after controlling for age, indicating a potential general effect of neuroinflammation on white matter microstructure. Further studies are warranted to determine the underlying mechanism driving the accelerated FA decline with age in schizophrenia.
我们研究了反映神经元健康和胶质细胞活化的体内神经化学标志物，以确定这些标志物是否能为精神分裂症中白质分数各向异性（FA）降低以及FA随年龄加速下降提供线索。精神分裂症患者和健康对照者完成了扩散张量成像以评估FA，并进行了质子磁共振波谱分析以评估同一额叶区域的神经化学代谢物。与健康对照组相比，精神分裂症患者的额叶FA显著降低，且随年龄下降得更快。在两组中，作为神经元完整性推定标志物的N-乙酰天门冬氨酸（NAA）和谷氨酸均随年龄下降，且患者组下降更为明显。作为胶质细胞标志物的肌醇在两组中均与FA呈负相关。即使在控制了所有代谢物后，精神分裂症中FA与年龄之间的关系仍然显著。FA、NAA和肌醇与年龄的关系似乎相互独立。即使在控制了年龄之后，FA与肌醇之间的关系在患者和对照中均独立存在，这表明神经炎症对白质微观结构可能存在普遍影响。有必要进行进一步研究以确定导致精神分裂症中FA随年龄加速下降的潜在机制。
