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.

Autor:	Korann V; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada., Panganiban KJ; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada., Stogios N; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada., Remington G; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Department of Psychological Clinical Science, University of Toronto Scarborough, Toronto, ON, Canada., Graff-Guerrero A; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Department of Psychological Clinical Science, University of Toronto Scarborough, Toronto, ON, Canada.; Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada., Chintoh A; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada., Hahn MK; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada., Agarwal SM; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.; Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada.
Jazyk:	angličtina
Zdroj:	Canadian journal of psychiatry. Revue canadienne de psychiatrie [Can J Psychiatry] 2024 Oct 21, pp. 7067437241290193. Date of Electronic Publication: 2024 Oct 21.
DOI:	10.1177/07067437241290193
Abstrakt:	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. Competing Interests: Declaration of Conflicting InterestsRemaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. SMA has received honoraria from HLS Therapeutics and Boehringer Ingelheim outside the submitted work. MKH has received honoraria from Alkermes and grants from Merck outside the submitted work. GR has received grants from HLS Therapeutics.
Databáze:	MEDLINE
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