Evidence of Neurovascular Water Exchange and Endothelial Vascular Dysfunction in Schizophrenia: An Exploratory Study

Authors

Eric L Goldwaser
Danny J J Wang
Bhim M Adhikari
Joshua Chiappelli
Xingfeng Shao
Jiaao Yu
Tong Lu
Shuo Chen
Wyatt Marshall
Alexa Yuen
Mark Kvarta
Yizhou Ma
Xiaoming Du
Si Gao
Osamah Saeedi
Heather Bruce
Patrick Donnelly
Hugh O'Neill
Alan R Shuldiner
Braxton D Mitchell
Peter Kochunov
L Elliot Hong

Publication Date

9-7-2023

Journal

Schizophrenia Bulletin

Abstract

BACKGROUND AND HYPOTHESIS: Mounting evidence supports cerebrovascular contributions to schizophrenia spectrum disorder (SSD) but with unknown mechanisms. The blood-brain barrier (BBB) is at the nexus of neural-vascular exchanges, tasked with regulating cerebral homeostasis. BBB abnormalities in SSD, if any, are likely more subtle compared to typical neurological insults and imaging measures that assess large molecule BBB leakage in major neurological events may not be sensitive enough to directly examine BBB abnormalities in SSD.

STUDY DESIGN: We tested the hypothesis that neurovascular water exchange (Kw) measured by non-invasive diffusion-prepared arterial spin label MRI (n = 27 healthy controls [HC], n = 32 SSD) is impaired in SSD and associated with clinical symptoms. Peripheral vascular endothelial health was examined by brachial artery flow-mediated dilation (n = 44 HC, n = 37 SSD) to examine whether centrally measured Kw is related to endothelial functions.

STUDY RESULTS: Whole-brain average Kw was significantly reduced in SSD (P = .007). Exploratory analyses demonstrated neurovascular water exchange reductions in the right parietal lobe, including the supramarginal gyrus (P = .002) and postcentral gyrus (P = .008). Reduced right superior corona radiata (P = .001) and right angular gyrus Kw (P = .006) was associated with negative symptoms. Peripheral endothelial function was also significantly reduced in SSD (P = .0001). Kw in 94% of brain regions in HC positively associated with peripheral endothelial function, which was not observed in SSD, where the correlation was inversed in 52% of brain regions.

CONCLUSIONS: This study provides initial evidence of neurovascular water exchange abnormalities, which appeared clinically associated, especially with negative symptoms, in schizophrenia.

Keywords

Humans, Schizophrenia, Water, Brain, Blood-Brain Barrier, White Matter

Comments

Supplementary Materials

PMID: 37078962