Plitman Eric, de la Fuente-Sandoval Camilo, Reyes-Madrigal Francisco, Chavez Sofia, Gómez-Cruz Gladys, León-Ortiz Pablo, Graff-Guerrero Ariel
Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada;
Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico;
Schizophr Bull. 2016 Mar;42(2):415-24. doi: 10.1093/schbul/sbv118. Epub 2015 Aug 28.
Glial disturbances are highly implicated in the pathophysiology of schizophrenia and may be linked with glutamatergic dysregulation. Myo-inositol (mI), a putative marker of glial cells, and choline (Cho), representative of membrane turnover, are both present in larger concentrations within glial cells than in neurons, and their elevation is often interpreted to reflect glial activation. Proton magnetic resonance spectroscopy ((1)H-MRS) allows for the evaluation of mI, Cho, glutamate, glutamate + glutamine (Glx), and N-acetylaspartate (NAA). A collective investigation of these measures in antipsychotic-naive patients experiencing their first nonaffective episode of psychosis (FEP) can improve the understanding of glial dysfunction and its implications in the early stages of schizophrenia. 3-Tesla (1)H-MRS (echo time = 35 ms) was performed in 60 antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls. mI, Cho, glutamate, Glx, and NAA were estimated using LCModel and corrected for cerebrospinal fluid composition within the voxel. mI, Cho, and glutamate were elevated in the FEP group. After correction for multiple comparisons, mI positively correlated with grandiosity. The relationships between mI and glutamate, and Cho and glutamate, were more positive in the FEP group. These findings are suggestive of glial activation in the absence of neuronal loss and may thereby provide support for the presence of a neuroinflammatory process within the early stages of schizophrenia. Dysregulation of glial function might result in the disruption of glutamatergic neurotransmission, which may influence positive symptomatology in patients with FEP.
神经胶质紊乱在精神分裂症的病理生理学中具有高度相关性，并且可能与谷氨酸能调节异常有关。肌醇（mI）是神经胶质细胞的一种假定标志物，而胆碱（Cho）代表膜更新，二者在神经胶质细胞中的浓度均高于神经元，其升高通常被解释为反映神经胶质激活。质子磁共振波谱（(1)H-MRS）可用于评估mI、Cho、谷氨酸、谷氨酸 + 谷氨酰胺（Glx）和N-乙酰天门冬氨酸（NAA）。对首次经历非情感性精神病发作（FEP）且未服用抗精神病药物的患者进行这些指标的综合研究，有助于加深对神经胶质功能障碍及其在精神分裂症早期阶段影响的理解。对60例首次发作FEP且未服用抗精神病药物的患者以及60名年龄和性别匹配的健康对照者进行了3特斯拉(1)H-MRS（回波时间 = 35毫秒）检查。使用LCModel估算mI、Cho、谷氨酸、Glx和NAA，并针对体素内的脑脊液成分进行校正。FEP组中mI、Cho和谷氨酸升高。在进行多重比较校正后，mI与夸大观念呈正相关。FEP组中mI与谷氨酸以及Cho与谷氨酸之间的关系更为正向。这些发现提示在无神经元丢失的情况下存在神经胶质激活，从而可能为精神分裂症早期存在神经炎症过程提供支持。神经胶质功能调节异常可能导致谷氨酸能神经传递中断，这可能影响FEP患者的阳性症状。
