Microvascular dysfunction in schizophrenia: a case–control study

Vetter, Martin; Martin, Billie-Jean; Fung, Michelle; Pajević, M; Anderson, Todd J.; Raedler, Thomas J.

doi:10.1038/npjschz.2015.23

Cited by 17 publications

(9 citation statements)

References 55 publications

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“…Overall, these findings are consistent with the proposal that schizophrenia involves microvascular dysfunction, 2 and that there are significant vascular-ischemic effects of the disorder. 5,6 The mechanisms involved in this remain unclear, however.…”

Section: Dovepresssupporting

confidence: 89%

“…This was described long ago by Bleuler, who noted "The fragility of the blood vessels which appears in many schizophrenics, both acute and chronic, seems to indicate a real vascular pathology". 1 More recently, studies indicate both peripheral 2 and central nervous system 3 microvasculature abnormalities, in addition to elevated rates of cardiac disease 4 and a significant overrepresentation of genes involved in vascular function among schizophrenia candidate risk genes. 5 Based on this and other evidence, it has been suggested that schizophrenia is an adult vascular-ischemic disorder, 5 with vascular changes occurring secondary to neuroinflammatory processes and eventually leading to changes in neural function and neuroanatomy.…”

Section: Introductionmentioning

confidence: 99%

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Retinal Microvasculature in Schizophrenia

Silverstein¹,

Lai²,

Green³

et al. 2021

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Purpose: Schizophrenia is associated with alterations in neural structure and function of the retina that are similar to changes seen in the retina and brain in multiple neurodegenerative disorders. Preliminary evidence suggests that retinal microvasculature may also be compromised in schizophrenia. The goal of this study was to determine, using optical coherence tomography angiography (OCTA), whether 1) schizophrenia is associated with alterations in retinal microvasculature density; and 2) microvasculature reductions are associated with retinal neural layer thinning and performance on a measure of verbal IQ. Patients and Methods: Twenty-eight outpatients with schizophrenia or schizoaffective disorder and 37 psychiatrically healthy control subjects completed OCT and OCTA exams, and the Wechsler Test of Adult Reading. Results: Schizophrenia patients were characterized by retinal microvasculature density reductions, and enlarged foveal avascular zones, in both eyes. These microvascular abnormalities were generally associated with thinning of retinal neural (macular and peripapillary nerve fiber layer) tissue (but the data were stronger for the left than the right eye) and lower scores on a proxy measure of verbal IQ. First-and later-episode patients did not differ significantly on OCTA findings. Conclusion:The retinal microvasculature impairments seen in schizophrenia appear to be a biomarker of overall brain health, as is the case for multiple neurological conditions. Additional research is needed, however, to clarify contributions of social disadvantage and medical comorbidities to the findings.

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Section: Dovepresssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Retinal Microvasculature in Schizophrenia

Silverstein¹,

Lai²,

Green³

et al. 2021

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“…Furthermore, several prospective studies and meta-analyses have demonstrated the presence of endothelial dysfunction in all phases of BPD [78], reviewed in [79]. Similar findings have been reported by researchers investigating the presence of endothelial dysfunction in SZ [80,81] and MDD [6,82].…”

Section: Introductionsupporting

confidence: 75%

Endothelial dysfunction in neuroprogressive disorders—causes and suggested treatments

Morris

Puri²,

Olive

et al. 2020

BMC Med

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Background Potential routes whereby systemic inflammation, oxidative stress and mitochondrial dysfunction may drive the development of endothelial dysfunction and atherosclerosis, even in an environment of low cholesterol, are examined. Main text Key molecular players involved in the regulation of endothelial cell function are described, including PECAM-1, VE-cadherin, VEGFRs, SFK, Rho GEF TRIO, RAC-1, ITAM, SHP-2, MAPK/ERK, STAT-3, NF-κB, PI3K/AKT, eNOS, nitric oxide, miRNAs, KLF-4 and KLF-2. The key roles of platelet activation, xanthene oxidase and myeloperoxidase in the genesis of endothelial cell dysfunction and activation are detailed. The following roles of circulating reactive oxygen species (ROS), reactive nitrogen species and pro-inflammatory cytokines in the development of endothelial cell dysfunction are then described: paracrine signalling by circulating hydrogen peroxide, inhibition of eNOS and increased levels of mitochondrial ROS, including compromised mitochondrial dynamics, loss of calcium ion homeostasis and inactivation of SIRT-1-mediated signalling pathways. Next, loss of cellular redox homeostasis is considered, including further aspects of the roles of hydrogen peroxide signalling, the pathological consequences of elevated NF-κB, compromised S-nitrosylation and the development of hypernitrosylation and increased transcription of atherogenic miRNAs. These molecular aspects are then applied to neuroprogressive disorders by considering the following potential generators of endothelial dysfunction and activation in major depressive disorder, bipolar disorder and schizophrenia: NF-κB; platelet activation; atherogenic miRs; myeloperoxidase; xanthene oxidase and uric acid; and inflammation, oxidative stress, nitrosative stress and mitochondrial dysfunction. Conclusions Finally, on the basis of the above molecular mechanisms, details are given of potential treatment options for mitigating endothelial cell dysfunction and activation in neuroprogressive disorders.

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“…The combination of Clinical Microangiology and "Angiobiopathy" theory (Stagnaro, 2009a), allows to consider schizophrenia as a disease resulting from a neurological and microvascular-based dysfunction (i.e., secondary to an impaired endothelial function (Vetter et al, 2015) associated with mitochondrial functional impairment (i.e., the congenital alteration of mit-DNA in related neuronal cells). Microvascular functions measured by fractal dimension of microvessel oscillations, in accordance with the above quoted papers, show physiological complex behaviour (deterministic chaos), while loss of their complexity is sign of pathology (or predisposition to disease).…”

Section: Mitochondrialmentioning

confidence: 99%