Peripheral Microvascular and Cerebral White Matter Dysfunction in Schizophrenia: Implications of a Body-Brain Endothelial Pathophysiology

Authors

• Eric L Goldwaser
• Alexa Yuen
• Wyatt Marshall
• Bhim M Adhikari
• Joshua Chiappelli
• Andrew van der Vaart
• Mark Kvarta
• Yizhou Ma
• Xiaoming Du
• Si Gao
• Heather Bruce
• Patrick Donnelly
• Braxton Mitchell
• Charles Hong
• Danny J J Wang
• Peter Kochunov
• L Elliot Hong

Language

English

Publication Date

11-10-2025

Journal

Schizophrenia Bulletin

DOI

10.1093/schbul/sbaf020

PMID

40036787

PMCID

PMC12597496

PubMedCentral® Posted Date

2-28-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background and hypothesis: Schizophrenia spectrum disorder (SSD) is a chronic neuropsychiatric illness accompanied by significant brain structural and functional abnormalities and higher rate of cardio- and cerebrovascular comorbidities. We hypothesized that genetic and environmental risk factors that led to SSD act throughout the body and demonstrated the association between lower integrity of peripheral vascular endothelium and white matter (WM) microstructure.

Study design: Microvascular endothelial function was evaluated using brachial artery post-occlusive reactive hyperemia (PORH), in which endothelial responses are measured under reduced blood flow and after blood flow is restored. White matter microstructure was assessed by multi-shell diffusion tensor imaging in n = 48 healthy controls (HCs) and n = 46 SSD.

Study results: Patients showed significantly lower PORH (F1,90 = 5.31, P = .02) effect and lower whole-brain fractional anisotropy (FA) values by diffusion imaging (F1,84 = 7.46, P = .008) with a group × post-occlusion time interaction effect (F3,90 = 4.58, P = .02). The PORH and whole-brain FA were significantly correlated in the full sample (r = 0.28, P = .01) and in SSD (r = 0.4, P = .008) separately, but not HC (r = 0.18, P = .28).

Conclusions: This study demonstrated, for the first time, significantly lower integrity of vascular endothelium in participants with SSD and showed that it is associated with WM microstructural abnormalities. Together, these findings support the need for a more holistic, body-brain approach to study the pathophysiology of SSD.

Keywords

Humans, Male, Female, Schizophrenia, Diffusion Tensor Imaging, Adult, White Matter, Endothelium, Vascular, Microvessels, Middle Aged, Hyperemia, Brachial Artery, Young Adult, psychosis, blood flow, vascular, blood vessels, microstructure, mechanism

Published Open-Access

yes

Recommended Citation

Goldwaser, Eric L; Yuen, Alexa; Marshall, Wyatt; et al., "Peripheral Microvascular and Cerebral White Matter Dysfunction in Schizophrenia: Implications of a Body-Brain Endothelial Pathophysiology" (2025). Faculty, Staff and Student Publications. 4391.
https://digitalcommons.library.tmc.edu/uthmed_docs/4391