Vittal Korann, Kristoffer J Panganiban, Nicolette Stogios, Gary Remington, Ariel Graff-Guerrero, Araba Chintoh, Margaret K Hahn, Sri Mahavir Agarwal
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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.</p><p><strong>Methods: </strong>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 <i>x</i>-, <i>y</i>-, and <i>z</i>-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.</p><p><strong>Results: </strong>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 <i>P</i> < 0.005). Significant differences were also observed between the <i>x</i> and <i>y</i> projections/associations between patients and healthy controls (<i>P</i> < 0.001). Furthermore, we did not find any significant correlations (all <i>P</i> > 0.05) between the DTI-ALPS index with age, body mass index, symptomatology, and metabolic parameters.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":55283,"journal":{"name":"Canadian Journal of Psychiatry-Revue Canadienne De Psychiatrie","volume":" ","pages":"7067437241290193"},"PeriodicalIF":3.3000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562879/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders Minimally Exposed to Antipsychotics: La dérégulation du système glymphatique en présence de troubles psychotiques chez des patients peu exposés à des antipsychotiques.\",\"authors\":\"Vittal Korann, Kristoffer J Panganiban, Nicolette Stogios, Gary Remington, Ariel Graff-Guerrero, Araba Chintoh, Margaret K Hahn, Sri Mahavir Agarwal\",\"doi\":\"10.1177/07067437241290193\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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 <i>x</i>-, <i>y</i>-, and <i>z</i>-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.</p><p><strong>Results: </strong>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 <i>P</i> < 0.005). Significant differences were also observed between the <i>x</i> and <i>y</i> projections/associations between patients and healthy controls (<i>P</i> < 0.001). 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引用次数: 0
摘要
目的:影响精神病谱系障碍的病理生理机制在很大程度上尚属未知。甘油系统是清除大脑废物的途径,近来被认为与精神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受到干扰。对精神病谱系障碍中的脑 glymphatic 系统进行的初步研究报告了其紊乱情况,但由于研究对象包括接受过抗精神病药物治疗的患者,研究结果受到了药物影响的干扰。在这项研究中,我们使用沿血管周围空间的弥散张量成像分析(DTI-ALPS)技术,测量了抗精神病药物暴露程度极低的精神分裂症谱系障碍患者和健康对照组样本中甘油系统的功能:研究对象包括13名抗精神病药物轻度暴露(过去3个月/一生中暴露于2周抗精神病药物)的精神病谱系障碍患者和114名健康对照者。我们对投射纤维和联结纤维沿 x、y 和 z 轴的水扩散指标进行了量化,得出了 DTI-ALPS 指数,该指数是脑水活动的代表。使用双向方差分析对组间差异进行了分析,并对年龄和性别进行了控制。采用偏相关法评估ALPS指数与临床变量之间的关联:分析结果显示,抗精神病药物-轻度暴露的精神病谱系障碍患者的大脑两半球和全脑的DTI-ALPS指数值低于健康对照组(患者与健康对照组之间的所有P x和Y投影/关联(P P > 0.05)):结论:本研究表明,在抗精神病药物轻度暴露的精神病谱系障碍患者中,甘油系统失调。了解影响甘油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,因为正常的大脑功能需要适当的废物清除。
The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders Minimally Exposed to Antipsychotics: La dérégulation du système glymphatique en présence de troubles psychotiques chez des patients peu exposés à des antipsychotiques.
Objective: 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.
Methods: 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 x-, y-, and z-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.
Results: 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 P < 0.005). Significant differences were also observed between the x and y projections/associations between patients and healthy controls (P < 0.001). Furthermore, we did not find any significant correlations (all P > 0.05) between the DTI-ALPS index with age, body mass index, symptomatology, and metabolic parameters.
Conclusion: 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.
期刊介绍:
Established in 1956, The Canadian Journal of Psychiatry (The CJP) has been keeping psychiatrists up-to-date on the latest research for nearly 60 years. The CJP provides a forum for psychiatry and mental health professionals to share their findings with researchers and clinicians. The CJP includes peer-reviewed scientific articles analyzing ongoing developments in Canadian and international psychiatry.