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Increased Activity of the Glymphatic System in First-Episode Psychosis: Relationship With Cortical Thinning
Emily Alder1, Kahiau Among1, Colton A Olexa1
1Nationwide Children's Hospital, Columbus, Ohio.
Insights
Pediatric first-episode psychosis (FEP) shows increased glymphatic system (GS) activity and cortical thinning, unlike adult schizophrenia findings. This suggests unique developmental or disease-phase impacts on brain function in adolescents with FEP.
Area of Science:
- Neuroscience
- Psychiatry
- Developmental Biology
Background:
- First-episode psychosis (FEP) in pediatric patients presents a critical opportunity for intervention to prevent long-term disability.
- Understanding psychosis biomarkers is crucial for clarifying pathophysiology, guiding treatment, and improving patient prognostication.
- The glymphatic system (GS) is being investigated as a potential mechanistic biomarker in neurological and psychiatric conditions.
Purpose of the Study:
- To evaluate the glymphatic system (GS) as a potential biomarker in adolescent FEP.
- To assess if developmental processes influence GS function and cortical thinning in FEP adolescents.
- To explore the impact of age on GS function and cortical thinning in this population.
Main Methods:
- Recruited 21 FEP patients (PRP) and compared them to 42 community control participants (CCP).
- Utilized magnetic resonance imaging (MRI) to acquire T1 and diffusion-weighted sequences.
- Calculated analysis along the perivascular space (ALPS) as a proxy for GS activity and compared whole-brain cortical thickness using Freesurfer.
Main Results:
- FEP patients exhibited significant reductions in cortical thickness compared to controls, consistent with prior research.
- Contrary to expectations, FEP patients showed significantly elevated ALPS, indicating increased GS functioning.
- Cortical thinning was found to partially explain the observed ALPS levels in FEP patients.
Conclusions:
- Pediatric FEP patients demonstrate increased GS activation, contrasting with reduced GS function observed in adult schizophrenia.
- The elevated GS activity may be linked to excessive cortical thinning, though the causal relationship requires further investigation.
- Findings suggest differential GS responses based on disease phase or developmental factors, highlighting unique roles of GS and cortical thinning in pediatric FEP.
Objective:
First-episode psychosis (FEP) in pediatric onset is a pivotal window for preventing chronic disability and optimizing long-term outcomes. Improved understanding of psychosis biomarkers is essential to clarify the pathophysiology, guide individualized intervention, and improve prognostication for patients. We evaluated the glymphatic system (GS) as a potential mechanistic biomarker and assessed whether developmental processes influence GS function and cortical thinning in a cohort of FEP adolescents. We also explored the impact of age on GS function and cortical thinning.
Method:
A total of 21 FEP patient research participants (PRP) were recruited from a Psychiatry and Behavioral Health unit. The experimental battery included clinical and neuropsychological assessments and a magnetic resonance imaging session in which both T1 and diffusion-weighted sequences were acquired. PRP were compared to a normative set of 42 community control participants (CCP) from the same scanner. Across both groups, analysis along the perivascular space (ALPS), an approximation of glymphatic activity, was generated from the diffusion images, and whole-brain cortical thickness was compared between groups using Freesurfer software and statistical models.
Results:
Consistent with previous findings, significant and widespread reductions in cortical thickness were evident in the FEP population relative to the CCP. However, in contrast to expectations, ALPS was significantly elevated in PRP, suggesting increased GS functioning. Cortical thinning partially explained ALPS.
Conclusion:
In contrast to the few published studies in adults with schizophrenia, which have found significant reductions in ALPS, these results suggest that pediatric PRP with FEP have increased activation of the GS. Our findings suggest that this may relate to excessive cortical thinning in some brain regions (a hypothesis that we are currently exploring), although the directionality of this relationship is unclear. These findings may further indicate to a differential GS response in early vs late phases of disease or other differential pathologies related to development or disease phase, and to a differential role of GS and cortical thinning across groups.
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