Reduced glymphatic clearance in early psychosis
Poster No:
2104
Submission Type:
Abstract Submission
Authors:
Lin Hua1,2, Xinglin Zeng2,1, Kaixi Zhang2,1, Zhiying Zhao2, Zhen Yuan2,1
Institutions:
1Faculty of Health Sciences, University of Macau, Taipa, Macau, 2Centre for Cognitive and Brain Sciences, University of Macau, Taipa, Macau
First Author:
Lin Hua
Faculty of Health Sciences, University of Macau|Centre for Cognitive and Brain Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Faculty of Health Sciences, University of Macau|Centre for Cognitive and Brain Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Co-Author(s):
Xinglin Zeng
Centre for Cognitive and Brain Sciences, University of Macau|Faculty of Health Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Centre for Cognitive and Brain Sciences, University of Macau|Faculty of Health Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Kaixi Zhang
Centre for Cognitive and Brain Sciences, University of Macau|Faculty of Health Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Centre for Cognitive and Brain Sciences, University of Macau|Faculty of Health Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Zhen Yuan
Centre for Cognitive and Brain Sciences, University of Macau|Faculty of Health Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Centre for Cognitive and Brain Sciences, University of Macau|Faculty of Health Sciences, University of Macau
Taipa, Macau|Taipa, Macau
Introduction:
Early psychosis (EP) represents a pivotal period for intervention, characterized by initial psychotic episodes, cognitive decline, and progressive functional impairment. The glymphatic system-a macroscopic waste clearance pathway in the brain reliant on cerebrospinal fluid (CSF) dynamics-has been implicated in various neuroinflammatory and neurodegenerative disorders. Dysfunction of this system may contribute to the pathophysiology of EP. Blood-oxygen-level-dependent (BOLD) signal coupling with ventricular CSF flow, a recently proposed biomarker for glymphatic function, offers a non-invasive approach to investigating glymphatic clearance impairments in psychosis. This study aims to elucidate the role of BOLD-CSF coupling deficits in EP and their associations with brain structural changes, cognitive decline and symptom severity.
Methods:
Participants (n = 137; age = 23.86 ± 4.16 years; 51 females) were selected from the Human Connectome Project for Early Psychosis (HCP-EP). The current cohort included 49 healthy controls (HCs), 67 non-affective psychosis (NAP), and 21 affective psychosis (AP) patients diagnosed according to DSM-5 criteria. Structural MRI (sMRI) and resting-state functional MRI (rs-fMRI) were acquired using 3T Siemens MAGNETOM Prisma scanners. Global and voxel-wise BOLD-CSF coupling was quantified using cross-correlation analyses across time lags (−12s to +12s). In addition, high-order cognitive networks (default mode and frontoparietal) and low-order sensory-motor networks (somatomotor and visual) were analyzed separately. Finally, associations between BOLD-CSF coupling, brain morphology (cortical thickness, CSF volume), cognitive function (NIH Toolbox), and psychotic symptoms (PANSS, PROMIS-A-SF) were examined using linear regression and mixed-effects models.
·Figure 1. Characterizing BOLD-CSF coupling in HCP-EP dataset.
Results:
Global BOLD-CSF coupling was significantly reduced in EP compared to HCs (p < 0.05), with AP patients exhibiting the most severe impairments. High-order networks showed pronounced deficits, particularly in the default mode network (DMN) and frontoparietal network, with a 15-20% reduction in coupling strength compared to HCs. In contrast, low-order networks such as the somatomotor and visual regions exhibited preserved coupling.
Coupling delays were significantly longer in psychosis groups, with a mean delay of +3.8 seconds in AP patients compared to +3.2 seconds in HCs (p = 0.01). Morphological analyses revealed a significant negative correlation between global coupling strength and cortical thickness (r = −0.24, p = 0.006), and a positive correlation with CSF volume (r = 0.28, p < 0.001). Regional coupling deficits in high-order networks were associated with reduced cortical thickness, particularly in prefrontal and parietal regions.
Cognitively, weaker global BOLD-CSF coupling predicted poorer performance across multiple domains, including fluid intelligence (β = −0.0078, p = 0.006), total cognition (β = −0.0093, p < 0.001), and working memory (β = −0.0294, p < 0.001). Symptomatically, lower coupling strength was associated with greater psychotic symptom severity (PANSS: β = 0.0051, p = 0.006) and higher anxiety levels (PROMIS-A-SF: β = 0.0117, p = 0.002). These findings suggest a potential mechanistic link between glymphatic dysfunction, cognitive deficits, and symptomatology in psychosis.
Coupling delays were significantly longer in psychosis groups, with a mean delay of +3.8 seconds in AP patients compared to +3.2 seconds in HCs (p = 0.01). Morphological analyses revealed a significant negative correlation between global coupling strength and cortical thickness (r = −0.24, p = 0.006), and a positive correlation with CSF volume (r = 0.28, p < 0.001). Regional coupling deficits in high-order networks were associated with reduced cortical thickness, particularly in prefrontal and parietal regions.
Cognitively, weaker global BOLD-CSF coupling predicted poorer performance across multiple domains, including fluid intelligence (β = −0.0078, p = 0.006), total cognition (β = −0.0093, p < 0.001), and working memory (β = −0.0294, p < 0.001). Symptomatically, lower coupling strength was associated with greater psychotic symptom severity (PANSS: β = 0.0051, p = 0.006) and higher anxiety levels (PROMIS-A-SF: β = 0.0117, p = 0.002). These findings suggest a potential mechanistic link between glymphatic dysfunction, cognitive deficits, and symptomatology in psychosis.
·Figure 2. gBOLD-CSF coupling strength is associated with age and varies between diagnoses.
Conclusions:
This study establishes reduced BOLD-CSF coupling as a novel biomarker for glymphatic dysfunction in early psychosis, with preferential impairment in high-order cortical networks. The observed associations with cortical thinning, increased CSF volume, cognitive decline, and symptom severity highlight the pathophysiological relevance of glymphatic dysfunction in psychosis. These findings underscore the potential of targeting glymphatic pathways for therapeutic intervention, offering insights into novel strategies for mitigating cognitive and symptomatic progression in psychosis.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Physiology, Metabolism and Neurotransmission:
Cerebral Metabolism and Hemodynamics 1
Keywords:
Cerebral Blood Flow
Cerebro Spinal Fluid (CSF)
FUNCTIONAL MRI
Other - Early Psychosis
1|2Indicates the priority used for review
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