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

Ali Abdolizadeh; Edgardo Torres-Carmona; Yasaman Kambari; Aron Amaev; Jianmeng Song; Fumihiko Ueno; Teruki Koizumi; Shinichiro Nakajima; Sri Mahavir Agarwal; Vincenzo De Luca; Philip Gerretsen; Ariel Graff-Guerrero

doi:10.1093/schbul/sbae060

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. doi: 10.1093/schbul/sbae060. Online ahead of print.

Authors

Ali Abdolizadeh^{1

2}, Edgardo Torres-Carmona^{1

2}, Yasaman Kambari^{1

2}, Aron Amaev^{1

2}, Jianmeng Song^{1

2}, Fumihiko Ueno^{1

3

4}, Teruki Koizumi^{1

3

5}, Shinichiro Nakajima^{1

4}, Sri Mahavir Agarwal^{2

3}, Vincenzo De Luca^{2

3}, Philip Gerretsen^{1

2

3

6}, Ariel Graff-Guerrero^{1

2

3

6}

Affiliations

¹ Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
² Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
³ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁴ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
⁵ Department of Psychiatry, National Hospital Organization Shimofusa Psychiatric Medical Center, Chiba, Japan.
⁶ Campbell Family Mental Health Research Institute, CAMH, Toronto, ON, Canada.

PMID: 38748498
DOI: 10.1093/schbul/sbae060

Abstract

Background and hypothesis: The glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index.

Study design: Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity.

Study results: MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01).

Conclusions: Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD.

Keywords: DTI-ALPS; glymphatic clearance; macromolecule; schizophrenia; waste accumulation.

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Abstract

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