Why the study?
Schizophrenia spectrum disorder carries high cardio- and cerebrovascular comorbidities, leading to the hypothesis that systemic risk factors link peripheral vascular endothelial dysfunction with cerebral white matter microstructure abnormalities.
Is schizophrenia spectrum disorder associated with impaired peripheral microvascular endothelial function and cerebral white matter microstructural abnormalities compared to healthy controls?
Is schizophrenia spectrum disorder associated with impaired peripheral microvascular endothelial function and cerebral white matter microstructural abnormalities compared to healthy controls?
Patients with schizophrenia spectrum disorder exhibit impaired peripheral microvascular endothelial function that correlates with cerebral white matter microstructural abnormalities, suggesting a systemic body-brain endothelial pathophysiology.
Answers are grounded in this paper and cite their sources.
SSD-associated microvascular impairment is hypothesis-generating; prospective studies needed before clinical or therapeutic implications.
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.
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Goldwaser et al. (2025) studied this question.
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