Background and Hypothesis Schizophrenia involves microstructural changes in white matter (WM) tracts. Oxidative stress is a key factor causing WM damage by hindering oligodendrocyte development and myelin maturation. Uric acid (UA), an endogenous antioxidant, may protect against oxidative stress. We investigated the effect of UA on WM connectivity in antipsychotic-naive or -free patients with early- or chronic-stage schizophrenia. Study Design A total of 192 patients with schizophrenia (122 recent-onset [ROS] and 70 chronic [CS]) and 107 healthy controls (HCs) participated in this study. Diffusion tensor imaging data and serum UA levels at baseline were obtained. Study Results Fractional anisotropy was lower in the widespread WM regions across the whole brain, and diffusivity measures were higher in both schizophrenia groups than in HCs. The CS group showed lower diffusivity in some WM tracts than the ROS or HC groups. The linear relationship of serum UA levels with axial and mean diffusivity in the right frontal region was significantly different between schizophrenia stages, which was driven by a negative association in the CS group. WM diffusivity associated with serum UA levels correlated with 8-week treatment responses only in patients with CS, suggesting UA to be protective against long-term schizophrenia. Conclusions UA may protect against the WM damage associated with the progression of schizophrenia by reducing oxidative stress and supporting WM repair against oxidative damage. These results provide insights into the positive role of UA and may facilitate the development of novel disease-modifying therapies.

中文翻译：

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尿酸对精神分裂症患者白质微结构和治疗反应的积极影响

背景和假设 精神分裂症涉及白质 (WM) 束的微观结构变化。氧化应激是通过阻碍少突胶质细胞发育和髓磷脂成熟而导致 WM 损伤的关键因素。尿酸 (UA) 是一种内源性抗氧化剂，可以防止氧化应激。我们研究了 UA 对未服用或未服用抗精神病药物的早期或慢性精神分裂症患者中 WM 连接的影响。研究设计 共有 192 名精神分裂症患者（122 名新发 [ROS] 和 70 名慢性 [CS]）和 107 名健康对照者 (HC) 参与了本研究。获得扩散张量成像数据和基线血清 UA 水平。研究结果 整个大脑中广泛分布的 WM 区域的分数各向异性较低，两个精神分裂症组的扩散率测量值均高于 HC。 CS 组在一些 WM 束中表现出比 ROS 或 HC 组更低的扩散率。血清 UA 水平与右额叶区域轴向和平均扩散率的线性关系在精神分裂症阶段之间存在显着差异，这是由 CS 组中的负相关驱动的。仅在 CS 患者中，与血清 UA 水平相关的 WM 扩散率与 8 周治疗反应相关，表明 UA 对长期精神分裂症具有保护作用。结论 UA 可能通过减少氧化应激并支持 WM 修复氧化损伤来预防与精神分裂症进展相关的 WM 损伤。这些结果提供了对 UA 积极作用的见解，并可能促进新型疾病缓解疗法的开发。