Korann Vittal, Panganiban Kristoffer J, Stogios Nicolette, Remington Gary, Graff-Guerrero Ariel, Chintoh Araba, Hahn Margaret K, Agarwal Sri Mahavir
Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Can J Psychiatry. 2025 Mar;70(3):260-270. doi: 10.1177/07067437241290193. Epub 2024 Oct 21.
The pathophysiological mechanisms influencing psychosis spectrum disorders are largely unknown. The glymphatic system, which is a brain waste clearance pathway, has recently been implicated in its pathophysiology and has also been shown to be disrupted in various neurodegenerative and vascular diseases. Initial studies examining the glymphatic system in psychosis spectrum disorders have reported disruptions, but the findings have been confounded by medication effects as they included antipsychotic-treated patients. In this study, we used diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) as a technique to measure the functionality of the glymphatic system in a sample of antipsychotic-minimally exposed patients with psychosis spectrum disorders and healthy controls.
The study included 13 antipsychotic-minimally exposed (2 weeks antipsychotic exposure in the past 3 months/lifetime) patients with psychosis spectrum disorders and 114 healthy controls. We quantified water diffusion metrics along the -, -, and -axes in both projection and association fibres to derive the DTI-ALPS index, a proxy for glymphatic activity. Between-group differences were analyzed using two-way ANCOVA controlling for age and sex. Partial correlations were used to assess the association between the ALPS index and clinical variables.
Analyses revealed that antipsychotic-minimally exposed psychosis spectrum disorder patients had a lower DTI-ALPS index value than healthy controls in both hemispheres and the whole brain (all < 0.005). Significant differences were also observed between the and projections/associations between patients and healthy controls ( < 0.001). Furthermore, we did not find any significant correlations (all > 0.05) between the DTI-ALPS index with age, body mass index, symptomatology, and metabolic parameters.
This study shows that the glymphatic system is dysregulated in antipsychotic-minimally exposed patients with psychosis spectrum disorders. Understanding the mechanisms that influence the glymphatic system may help to understand the pathophysiology of psychosis spectrum disorders as proper waste clearance is needed for normal brain functioning.
影响精神病谱系障碍的病理生理机制在很大程度上尚不清楚。脑淋巴系统是一种脑废物清除途径，最近被认为与该疾病的病理生理学有关，并且在各种神经退行性疾病和血管疾病中也被证明存在功能紊乱。最初对精神病谱系障碍患者脑淋巴系统的研究报告了功能紊乱，但由于研究对象包括接受抗精神病药物治疗的患者，研究结果受到药物作用的干扰。在本研究中，我们使用沿血管周围间隙的扩散张量成像分析（DTI-ALPS）技术，来测量抗精神病药物暴露最少的精神病谱系障碍患者和健康对照样本中脑淋巴系统的功能。
该研究纳入了13例抗精神病药物暴露最少（过去3个月/终生抗精神病药物暴露2周）的精神病谱系障碍患者和114名健康对照。我们在投射纤维和联合纤维中沿X、Y和Z轴量化水扩散指标，以得出DTI-ALPS指数，作为脑淋巴活动的一个替代指标。使用双向协方差分析控制年龄和性别来分析组间差异。偏相关分析用于评估ALPS指数与临床变量之间的关联。
分析显示，抗精神病药物暴露最少的精神病谱系障碍患者在两个半球和整个大脑中的DTI-ALPS指数值均低于健康对照（均P<0.005）。患者与健康对照在X和Y投射/联合之间也观察到显著差异（P<0.001）。此外，我们未发现DTI-ALPS指数与年龄、体重指数、症状学和代谢参数之间存在任何显著相关性（均P>0.05）。
本研究表明，抗精神病药物暴露最少的精神病谱系障碍患者的脑淋巴系统功能失调。了解影响脑淋巴系统的机制可能有助于理解精神病谱系障碍的病理生理学，因为正常的脑功能需要适当的废物清除。
