The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders
Poster No:
535
Submission Type:
Abstract Submission
Authors:
Vittal Korann1, Kristoffer Panganiban1, Nicolette Stogios2, Gary Remington3, Ariel Graff-Guerrero3, Araba Chintoh4, Margaret Hahn3, Sri Mahavir Agarwal3
Institutions:
1University of Toronto, Toronto, Ontario, 2Center for Addiction and Mental Health, Toronto, Toronto, 3Institute of Medical Sciences, University of Toronto, Toronto, Ontario, 4Centre for Addiction and Mental Health (CAMH), Toronto, Ontario
First Author:
Co-Author(s):
Introduction:
The pathophysiological mechanisms influencing psychosis spectrum disorders (PSDs) are largely unknown. The glymphatic system (GS), 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 (Jessen et. al., 2015). Initial studies examining the glymphatic system in PSDs have reported disruptions, but the findings have been confounded by medication effects as they included antipsychotic (AP)-treated patients (Ericek et. al., 2022; Wu et. al., 2020). Moreover, in patients with first-episode psychosis, task-based and resting-state functional imaging studies have reported that AP treatment can normalize functional dysconnectivity involving the frontal and temporal regions (Yang et. Al., 2021; Keedy et. Al., 2015). As such, AP usage represents a potentially important confounding factor in this field of study. To avoid this confounding factor, we measured the functionality of the GS in a sample of AP-minimally exposed patients with PSDs and healthy controls (HCs) by utilizing the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) technique (Taoka et al., 2017; Abdolizadeh at. al., 2024).
Methods:
The study included 13 AP-minimally exposed (≤2 weeks AP exposure in the past 3 months/lifetime) patients with PSDs and 114 HCs. The 64-direction diffusion weighted images (DWI) of both groups were processed by combining both FSL and MRtrix3 commands. The superior corona radiata (SCR) and the superior longitudinal fasciculus (SLF) were recognized as the projection and association fibers at the level of the lateral ventricle body, respectively, based on the JHU-ICBM-DTI-81-white-matter Labeled Atlas. The bilateral SCR and SLF areas were defined as spheres with a 5mm diameter, and these ROIs were applied to the diffusivity maps of all participants. The bilateral SLF and SCR diffusivity values were automatically computed along the x-, y-, and z-axis (i.e., Dxx, Dyy, and Dzz) for the DTI-ALPS calculation. 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. 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 AP-minimally exposed patients had a significantly lower DTI-ALPS index of the left and right hemispheres and the whole brain compared to HCs, even after adjusting for age and sex (Falps_L = 11.09, p = 0.001; Falps_R = 10.92, p = 0.001; Falps = 13.06, p < 0.001). The effect sizes for the hemispheres and whole brain are: left (ηp2 = 0.112), right (ηp2 = 0.134) and whole brain (ηp2 = 0.142). The diffusivities along the x-axis of both projection and association fibers, in both the left and right hemispheres, were also lower in AP-minimally exposed patients than in HCs (Fproj_L = 54.49, p < 0.001; Fproj_R = 70.268, p < 0.001; Fassoc_L = 36.02, p < 0.001; Fassoc_R = 56.01, p < 0.001). In addition, the diffusivities along the y-axis of projection fibers in both the left and right hemispheres were lower in AP-minimally exposed patients when compared to HCs (Fproj_L = 27.63, p < 0.001; Fproj_R = 30.87, p < 0.001). Furthermore, we did not find any significant correlations (all p > 0.05) between the DTI-ALPS index with age, BMI, symptomatology, and metabolic parameters.
·Comparisons of DTI-ALPS index between AP-minimally exposed and HC groups in the left/right hemisphere and whole brain. **P < 0.005. Abbreviation: AP = antipsychotic; DTI-ALPS = diffusion tensor image
Conclusions:
Overall, this study demonstrates that AP-minimally treated PSDs have a lower DTI-ALPS index compared to HCs. This indicates that patients have a lower waste clearance in the GS as proper brain functioning may require a normal waste clearance. Understanding the mechanisms that influence the GS may help to understand the pathophysiology of PSDs as proper waste clearance is needed for normal brain functioning.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other
Keywords:
Psychiatric Disorders
Schizophrenia
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
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Yang, C, Tang, J, Liu, N, et al. The effects of antipsychotic treatment on the brain of patients with first-episode schizophrenia: a selective review of longitudinal MRI studies. Front Psychiatry. 2021. Jun 24;12: 593703.
Keedy SK, Reilly JL, Bishop JR, et al. Impact of antipsychotic treatment on Attention and motor learning systems in first-episode schizophrenia. Schizophr Bull. 2015;41(2).
Taoka T, Masutani Y, Kawai H, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases. Jpn J Radiol. 2017;35(4).
Abdolizadeh, A, Torres-Carmona, E, Kambari Y, et al. Evaluation of the glymphatic system in schizophrenia spectrum disorder using proton magnetic resonance spectroscopy measurement of brain macromolecule and diffusion tensor image analysis along the perivascular space index. Schizophr Bull. 2024 May 15: sbae060.