Sui Yu Veronica, Bertisch Hilary, Goff Donald C, Samsonov Alexey, Lazar Mariana
Department of Radiology, NYU Grossman School of Medicine, New York, NY, USA.
Department of Psychiatry, Northwell Zucker Hillside Hospital, Glen Oaks, NY, USA.
Mol Psychiatry. 2025 Jun;30(6):2739-2747. doi: 10.1038/s41380-024-02883-0. Epub 2025 Jan 8.
Myelin abnormalities in white matter have been implicated in the pathophysiology of psychotic spectrum disorders (PSD), which are characterized by brain dysconnectivity as a core feature. Among evidence from in vivo MRI studies, diffusion imaging findings have largely supported disrupted white matter integrity in PSD; however, they are not specific to myelin changes. Using a multimodal imaging approach, the current study aimed to further delineate myelin and microstructural changes in the white matter of a young PSD cohort. We utilized quantitative magnetization transfer (qMT) imaging combined with advanced diffusion imaging to estimate specific myelin-related biophysical properties in 51 young adult PSD patients compared with 38 age-matched healthy controls. The macromolecular proton fraction (MPF) obtained from qMT was used as a specific marker of myelin content. Additionally, MPF was employed along with diffusion metrics of axonal density (v) and extra-cellular volume fraction to derive the g-ratio, a measure of relative myelin sheath thickness defined as the ratio of inner to outer axonal diameter. Compared to controls, we observed a widespread MPF reduction and localized g-ratio increase in patients, primarily those with a diagnosis of schizophrenia or depressive schizoaffective disorder. No between-group differences were noted in v, suggesting similar axonal densities across groups. Correlation analysis revealed that lower MPF was significantly related to poorer working memory performance in PSD, while the HC group showed a positive association for working memory with both g-ratio and v. The pattern of changes observed in our multimodal imaging markers suggests that PSD, depending on symptomatology, is characterized by specific alterations in white matter integrity and myelin-axonal geometry of major white matter tracts, which may impact working memory function. These findings provide a more detailed view of myelin-related white matter changes in early stages of PSD.
白质中的髓鞘异常与精神分裂症谱系障碍（PSD）的病理生理学有关，PSD的核心特征是大脑连接障碍。在体内MRI研究的证据中，扩散成像结果在很大程度上支持了PSD中白质完整性的破坏；然而，它们并非特定于髓鞘变化。本研究采用多模态成像方法，旨在进一步描绘年轻PSD队列白质中的髓鞘和微观结构变化。我们利用定量磁化传递（qMT）成像结合先进的扩散成像，对51名年轻成年PSD患者与38名年龄匹配的健康对照者的特定髓鞘相关生物物理特性进行评估。从qMT获得的大分子质子分数（MPF）被用作髓鞘含量的特定标志物。此外，MPF与轴突密度（v）和细胞外体积分数的扩散指标一起用于推导g比率，g比率是一种相对髓鞘厚度的测量方法，定义为轴突内径与外径之比。与对照组相比，我们观察到患者中MPF普遍降低，g比率局部升高，主要是那些被诊断为精神分裂症或抑郁性分裂情感障碍的患者。各组之间在v方面未观察到差异，表明各组之间轴突密度相似。相关性分析显示，较低的MPF与PSD中较差的工作记忆表现显著相关，而健康对照组中工作记忆与g比率和v均呈正相关。我们在多模态成像标志物中观察到的变化模式表明，PSD根据症状表现，其特征是主要白质束的白质完整性和髓鞘 - 轴突几何结构发生特定改变，这可能会影响工作记忆功能。这些发现为PSD早期与髓鞘相关的白质变化提供了更详细的视角。
