Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Psychiatry Res Neuroimaging. 2018 Nov 30;281:101-106. doi: 10.1016/j.pscychresns.2018.06.003. Epub 2018 Jun 9.
Schizophrenia is a chronic, often progressive, disorder. Understanding the underlying neurobiology present in the early stages of the illness is as a pivotal step in designing targeted interventions aimed at arresting disease progression. The aim of our study was to examine neurometabolic changes in the dopamine rich associative striatum in medication-naïve first episode psychosis (FEP). We quantified neurometabolites in 14 FEP and 18 healthy controls (HC) matched on key demographic characteristics. Spectra from the voxel in the left associative striatum were acquired using a PRESS sequence (TR/TE = 2000/80 ms; 512 averages). MRS data were quantified in the time domain with AMARES in jMRUI. Choline was significantly elevated in FEP compared to HC. No significant alterations in other metabolites were observed. We did not observe correlations between metabolite levels and clinical characteristics in FEP. Here, we demonstrated elevated choline and a disruption of the relationship between N-acetyl-aspartate and Glx (glutamate + glutamine) in medication-naïve FEP patients in the left striatum indicating possible mitochondrial, membrane and glial dysfunction as an underlying pathological phenomenon. In addition, striatal choline shows promise as a biomarker for FEP that may have utility in clinical trials investigating target engagement in experimental regimens.
精神分裂症是一种慢性的、常常进行性的疾病。理解疾病早期存在的潜在神经生物学机制是设计旨在阻止疾病进展的靶向干预措施的关键步骤。我们的研究目的是研究未经药物治疗的首发精神分裂症(FEP)患者富含多巴胺的联合纹状体中的神经代谢变化。我们对 14 名 FEP 患者和 18 名健康对照者(HC)进行了定量分析,这些对照者在关键人口统计学特征上相匹配。使用 PRESS 序列(TR/TE=2000/80ms;512 次平均)在左联合纹状体的体素中采集了光谱。使用 jMRUI 中的 AMARES 在时域中对 MRS 数据进行了量化。与 HC 相比,FEP 中的胆碱明显升高。未观察到其他代谢物发生显著变化。我们未观察到 FEP 中代谢物水平与临床特征之间存在相关性。在这里,我们在未经药物治疗的 FEP 患者的左纹状体中证明了胆碱的升高以及 N-乙酰天冬氨酸和 Glx(谷氨酸+谷氨酰胺)之间关系的破坏,这表明可能存在线粒体、膜和神经胶质功能障碍作为潜在的病理现象。此外,纹状体中的胆碱有望成为 FEP 的生物标志物,在研究实验方案中药物靶点结合的临床试验中可能具有实用性。