Microvascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection

Katsel, Pavel; Roussos, Panos; Pletnikov, Mikhail; Haroutunian, Vahram

doi:10.1016/j.neubiorev.2017.04.003

Cited by 62 publications

(52 citation statements)

References 177 publications

(215 reference statements)

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“…Moreover, our results extend the Amph deleterious effects to the microvascular rearrangement in PFC ( Figure 2); supporting their region-specific toxicity as vascular network, modifications are closely related to inflammatory processes (Costa, Incio, & Soares, 2007). Similar vascular alterations have been previously described after Amph exposure (Occhieppo et al, 2017), chronic inflammatory disease (Dorr et al, 2012), and schizophrenia (Katsel, Roussos, Pletnikov, & Haroutunian, 2017).…”

Section: Glial Reactivity and Vascular Network Rearrangement Inducesupporting

confidence: 89%

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Marchese

Occhieppo

Basmadjian

et al. 2019

Eur J of Neuroscience

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Amphetamine‐induced neuroadaptations involve vascular damage, neuroinflammation, a hypo‐functioning prefrontal cortex (PFC), and cognitive alterations. Brain angiotensin II, through angiotensin type 1 receptor (AT1‐R), mediates oxidative/inflammatory responses, promoting endothelial dysfunction, neuronal oxidative damage and glial reactivity. The present work aims to unmask the role of AT1‐R in the development of amphetamine‐induced changes over glial and vascular components within PFC and hippocampus. Attention deficit was evaluated as a behavioral neuroadaptation induced by amphetamine. Brain microvessels were isolated to further evaluate vascular alterations after amphetamine exposure. Male Wistar rats were administered with AT1‐R antagonist, candesartan, followed by repeated amphetamine. After one week drug‐off period, animals received a saline or amphetamine challenge and were evaluated in behavioral tests. Afterward, their brains were processed for cresyl violet staining, CD11b (microglia marker), GFAP (astrocyte marker) or von Willebrand factor (vascular marker) immunohistochemistry, and oxidative/cellular stress determinations in brain microvessels. Statistical analysis was performed by using factorial ANOVA followed by Bonferroni or Tukey tests. Repeated amphetamine administration increased astroglial and microglial markers immunoreactivity, increased apoptotic cells, and promoted vascular network rearrangement at the PFC concomitantly with an attention deficit. Although the amphetamine challenge improved the attentional performance, it triggers detrimental effects probably because of the exacerbated malondialdehyde levels and increased heat shock protein 70 expression in microvessels. All observed amphetamine‐induced alterations were prevented by the AT1‐R blockade. Our results support the AT1‐R involvement in the development of oxidative/inflammatory conditions triggered by amphetamine exposure, affecting cortical areas and increasing vascular susceptibility to future challenges.

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Section: Glial Reactivity and Vascular Network Rearrangement Inducesupporting

confidence: 89%

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Marchese

Occhieppo

Basmadjian

et al. 2019

Eur J of Neuroscience

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“…Importantly, the results of the combined genome-wide expression analysis presented in this study are consistent with the occurrence of functionally relevant hypoperfusion of the frontal cortex during acute schizophrenic psychosis (meta-analyses 35,36 ). Furthermore, they agree with the recent findings by Katsel et al (2017) that genes involved in angiogenesis-related pathways are downregulated in brain samples from schizophrenic patients, suggesting an impaired cerebrovascular plexus 37 . In line with these findings, schizophrenic patients and their healthy family members show an increase of the anti-angiogenic factor "soluble fms-like tyrosine kinase-1 (sFlt-1)"…”

Section: Discussionsupporting

confidence: 92%

Cerebral ischemia-induced genes are increased in acute schizophrenia: an opportunity for clinical translation of genomic research findings

Moises

Hess²,

Binder

2017

Preprint

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Schizophrenia is a brain disorder of unknown etiology. Brain imaging studies have revealed evidence for hypoperfusion of the frontal cortex (hypofrontality) and progressive brain volume reduction in schizophrenic patients. Mild cerebral ischemia (oligemia) has been postulated as a cause of the disorder. If the ischemia hypothesis for the adult brain is correct, genes induced by cerebral ischemia should be increased in the frontal cortex of schizophrenic patients during acute psychosis. Here, we show for the first time through a combined analysis of gene expression data from all the studies of the Stanley Brain Collection covering the Brodmann area 46 of the frontal cortex and employing the well-established Affymetrix HGU133a microarray platform that genes upregulated by cerebral ischemia are significantly overexpressed (4.5-fold) in the frontal cortex of acute schizophrenic patients (representation factor (RF) 4.5, p < 0.0002) and to a lesser degree in chronic patients (RF 3.9, p < 0.008) in comparison to normal controls. Neurodevelopmental-, repair-, inflammation-and synapse-related genes showed no significant change. The difference between acute and chronic schizophrenic patients regarding cerebral ischemiainduced genes was highly significant (RF 2.8, p < 0.00007). The results reported here are in line with evidence from biochemical, cellular, electroencephalographic, brain imaging, cerebral near-infrared spectroscopy, vascular, and genetic association studies. In summary, our genomic analysis revealed a clear ischemic signature in the frontal cortex of schizophrenia patients, confirming the prediction of the adult ischemia hypothesis for this disorder. This finding suggests new possibilities for the treatment and prevention of schizophrenia.peer-reviewed)

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“…During embryonic development, common mechanisms underlie the vascularization of both the retina and the brain as the retina is embryologically an extension of the diencephalon . In both the retina and the brain, the vascular development is synchronous to neuronal development; the neurovascular coupling assures simultaneous generation of neuroblasts and blood vessels . In addition, endothelial cells play a critical role in migration and differentiation of oligodendrocytes .…”

Section: Discussionmentioning

confidence: 99%

Examination of retinal vascular trajectory in schizophrenia and bipolar disorder

Appaji

Nagendra

Chako

et al. 2019

Psychiatry Clin Neurosci

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Aim: Evidence suggests microvascular dysfunction (wider retinal venules and narrower arterioles) in schizophrenia (SCZ) and bipolar disorder (BD). The vascular development is synchronous with neuronal development in the retina and brain. The retinal vessel trajectory is related to retinal nerve fiber layer thinning and cerebrovascular abnormalities in SCZ and BD and has not yet been examined. Hence, in this study we examined the retinal vascular trajectory in SCZ and BD in comparison with healthy volunteers (HV).Methods: Retinal images were acquired from 100 HV, SCZ patients, and BD patients, respectively, with a non-mydriatic fundus camera. Images were quantified to obtain the retinal arterial and venous trajectories using a validated, semiautomated algorithm. Analysis of covariance and regression analyses were conducted to examine group differences. A supervised machine-learning ensemble of bagged-trees method was used for automated classification of trajectory values.Results: There was a significant difference among groups in both the retinal venous trajectory (HV: 0.17 AE 0.08; SCZ: 0.25 AE 0.17; BD: 0.27 AE 0.20; P < 0.001) and the arterial trajectory (HV: 0.34 AE 0.15; SCZ: 0.29 AE 0.10; BD: 0.29 AE 0.11; P = 0.003) even after adjusting for age and sex (P < 0.001). On post-hoc analysis, the SCZ and BD groups differed from the HV on retinal venous and arterial trajectories, but there was no difference between SCZ and BD patients. The machine learning showed an accuracy of 86% and 73% for classifying HV versus SCZ and BD, respectively.Conclusion: Smaller trajectories of retinal arteries indicate wider and flatter curves in SCZ and BD. Considering the relation between retinal/cerebral vasculatures and retinal nerve fiber layer thinness, the retinal vascular trajectory is a potential marker for SCZ and BD. As a relatively affordable investigation, retinal fundus photography should be further explored in SCZ and BD as a potential screening measure.

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Microvascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection

Cited by 62 publications

References 177 publications

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Cerebral ischemia-induced genes are increased in acute schizophrenia: an opportunity for clinical translation of genomic research findings

Examination of retinal vascular trajectory in schizophrenia and bipolar disorder

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