Background and Hypothesis Despite the well-documented structural and functional brain changes in schizophrenia, the potential role of glymphatic dysfunction remains largely unexplored. This study investigates the glymphatic system’s function in schizophrenia, utilizing diffusion tensor imaging (DTI) to analyze water diffusion along the perivascular space (ALPS), and examines its correlation with clinical symptoms. Study Design A cohort consisting of 43 people with schizophrenia and 108 healthy controls was examined. We quantified water diffusion metrics along the x-, y-, and z-axis in both projection and association fibers to derive the DTI-ALPS index, a proxy for glymphatic activity. The differences in the ALPS index between groups were analyzed using a 2-way ANCOVA controlling for age and sex, while partial correlations assessed the association between the ALPS index and clinical variables. Study Results People with schizophrenia showed a significantly reduced DTI-ALPS index across the whole brain and within both hemispheres (F = 9.001, P = .011; F = 10.024, P = .011; F = 5.927, P = .044; false discovery rate corrected), indicating potential glymphatic dysfunction in schizophrenia. The group by cognitive performance interaction effects on the ALPS index were not observed. Moreover, a lower ALPS index was associated with poorer cognitive performance on specific neuropsychological tests in people with schizophrenia. Conclusion Our study highlights a lower ALPS index in schizophrenia, correlated with more pronounced cognitive impairments. This suggests that glymphatic dysfunction may contribute to the pathophysiology of schizophrenia, offering new insights into its underlying mechanisms.

中文翻译：

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精神分裂症的淋巴系统功能障碍与认知障碍有关


背景和假设 尽管精神分裂症的大脑结构和功能变化有据可查，但淋巴功能障碍的潜在作用在很大程度上仍未得到探索。本研究调查了精神分裂症中的淋巴系统功能，利用弥散张量成像 （DTI） 分析水沿血管周围间隙 （ALPS） 的扩散，并检查其与临床症状的相关性。研究设计 检查了一个由 43 名精神分裂症患者和 108 名健康对照者组成的队列。我们量化了投影和关联纤维中沿 x 、 y 和 z 轴的水扩散指标，以得出 DTI-ALPS 指数，这是淋巴活动的代理。使用控制年龄和性别的 2 向 ANCOVA 分析组间 ALPS 指数的差异，而部分相关性评估 ALPS 指数与临床变量之间的关联。研究结果 精神分裂症患者在整个大脑和两个半球内的 DTI-ALPS 指数显着降低 （F = 9.001，P = .011;F = 10.024，P = .011;F = 5.927，P = .044;错误发现率校正），表明精神分裂症可能存在淋巴功能障碍。未观察到认知表现交互作用组对 ALPS 指数的影响。此外，较低的 ALPS 指数与精神分裂症患者在特定神经心理学测试中的认知表现较差相关。结论 我们的研究强调了精神分裂症患者的 ALPS 指数较低，与更明显的认知障碍相关。这表明淋巴功能障碍可能有助于精神分裂症的病理生理学，为其潜在机制提供新的见解。