Sackler Centre for Consciousness Science, University of Sussex, Falmer, Brighton; Division of Neuroscience, University of Sussex, Falmer, Brighton.
Brighton & Sussex Medical School, School of Psychology, University of Sussex, Falmer, Brighton; Sussex Partnership National Health Service Foundation Trust, United Kingdom.
Biol Psychiatry. 2017 Nov 15;82(10):716-725. doi: 10.1016/j.biopsych.2017.02.008. Epub 2017 Feb 17.
Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis.
Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication.
Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change.
Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis.
在早期精神病患者中，多个白质束的结构异常与连接中断一致，这是症状表现的神经病理学解释。我们应用先进的神经影像学技术来描述微观结构白质异常，以更深入地了解精神病的发展病因。
35 名首发精神病患者和 19 名健康对照者参与了一项使用神经丝取向分散和密度成像的定量神经影像学研究，这是一种多壳扩散加权磁共振成像技术，可区分白质纤维排列和几何形状与神经丝密度变化。还得出了分数各向异性（FA）和平均扩散系数图像。基于束的空间统计学比较了患者和对照组之间的白质结构，并测试了与年龄、症状严重程度和药物的关联。
首发精神病患者的多个连合束、皮质脊髓束和联合束的区域性 FA 较低。这些异常主要与神经丝密度降低的区域重叠，而不是与纤维束排列异常（取向弥散指数）有关。与活跃的症状没有直接关系。FA 在患者中随年龄的增加而降低，而在对照组中则不降低，这表明白质几何变化的加速作用。
神经丝密度的缺陷似乎对白质完整性异常在早期精神病中是基本的。在精神病学中首次应用神经丝取向分散和密度成像，我们发现，影响轴突纤维数量、密度和髓鞘形成的过程，而不是导致纤维组织空间破坏的过程，与精神病的病因有关。这与导致个体易患精神病的异常全脑结构连接的神经发育起源一致。
