Laboratory of Molecular Genetics and Biochemistry, Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, 634014, Russian Federation.
Department of Radiology, University of Washington, Seattle, WA, 98109, USA.
Transl Psychiatry. 2021 Jun 30;11(1):365. doi: 10.1038/s41398-021-01475-8.
Myelin deficiency is commonly recognized as an important pathological feature of brain tissues in schizophrenia (SZ). In this pilot study, global myelin content abnormalities in white matter (WM) and gray matter (GM) of SZ patients were non-invasively investigated using a novel clinically-targeted quantitative myelin imaging technique, fast macromolecular proton fraction (MPF) mapping. MPF maps were obtained from 23 healthy subjects and 31 SZ patients using a clinical 1.5T magnetic resonance imaging (MRI) scanner. Mean MPF in WM and GM was compared between the healthy control subjects and SZ patients with positive and negative leading symptoms using the multivariate analysis of covariance. The SZ patients had significantly reduced MPF in GM (p < 0.001) and WM (p = 0.02) with the corresponding relative decrease of 5% and 3%, respectively. The effect sizes for the myelin content loss in SZ relative to the control group were 1.0 and 1.5 for WM and GM, respectively. The SZ patients with leading negative symptoms had significantly lower MPF in GM (p < 0.001) and WM (p = 0.003) as compared to the controls and showed a significant MPF decrease in WM (p = 0.03) relative to the patients with leading positive symptoms. MPF in WM significantly negatively correlated with the disease duration in SZ patients (Pearson's r = -0.51; p = 0.004). This study demonstrates that chronic SZ is characterized by global microscopic brain hypomyelination of both WM and GM, which is associated with the disease duration and negative symptoms. Myelin deficiency in SZ can be detected and quantified by the fast MPF mapping method.
髓鞘缺失通常被认为是精神分裂症（SZ）脑组织的重要病理特征。在这项初步研究中，我们使用一种新的临床靶向定量髓鞘成像技术——快速大分子质子分数（MPF）映射，对 SZ 患者的白质（WM）和灰质（GM）的整体髓鞘含量异常进行了非侵入性研究。使用临床 1.5T 磁共振成像（MRI）扫描仪从 23 名健康受试者和 31 名 SZ 患者中获得 MPF 图谱。使用多元协方差分析比较有阳性和阴性前驱症状的健康对照和 SZ 患者的 WM 和 GM 中的平均 MPF。SZ 患者的 GM（p < 0.001）和 WM（p = 0.02）中的 MPF 显著降低，相应的相对减少分别为 5%和 3%。与对照组相比，SZ 患者的髓鞘含量损失的效应大小在 WM 和 GM 中分别为 1.0 和 1.5。与对照组相比，具有前驱阴性症状的 SZ 患者的 GM（p < 0.001）和 WM（p = 0.003）中的 MPF 显著降低，与具有前驱阳性症状的患者相比，WM 中的 MPF 显著降低（p = 0.03）。WM 中的 MPF 与 SZ 患者的病程呈显著负相关（Pearson r = -0.51；p = 0.004）。这项研究表明，慢性 SZ 表现为 WM 和 GM 的全脑微观少突胶质细胞髓鞘缺失，与疾病持续时间和阴性症状有关。快速 MPF 映射方法可检测和定量 SZ 中的髓鞘缺失。
