Angiogenesis in the pathophysiology of schizophrenia — A comprehensive review and a conceptual hypothesis

Lopes, Rui; Soares, Raquel; Coelho, Rui; Figueiredo-Braga, Margarida

doi:10.1016/j.lfs.2015.02.010

Cited by 24 publications

(19 citation statements)

References 279 publications

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“…Extensive reviews of structural and functional neuroimaging in SZ (Buchsbaum and Hazlett, 1998; Lopes et al, 2015), including discordant monozygotic twins (Weinberger et al, 1992), have demonstrated that abnormalities in brain hemodynamics are generally consistent with historical concept of hypofrontality in individuals with SZ (Berman et al, 1986) and reflect functional deficit of frontal cortex (Davidson and Heinrichs, 2003; Taylor, 1996; Weinberger et al, 1986). Frontal hypoperfusion has been consistently documented in clinical cases involving first episode, neuroleptic-naïve (Andreasen et al, 1997; Catafau et al, 1994; Erkwoh et al, 1997; Rubin et al, 1994) and untreated individuals with chronic SZ (Kim et al, 2000) suggesting that this characteristic is independent of the length of disease, its treatment and duration.…”

Section: Regional Brain Hemodynamic Changes Associated With Sz CLImentioning

confidence: 92%

Microvascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection

Katsel

Roussos

Pletnikov

et al. 2017

Neuroscience & Biobehavioral Reviews

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Schizophrenia (SZ) is a severe mental disorder with unknown etiology and elusive neuropathological and neurobiological features have been a focus of many theoretical hypotheses and empirical studies. Current genetic and neurobiology information relevant to SZ implicates neuronal developmental and synaptic plasticity abnormalities, and neurotransmitter, microglial and oligodendrocytes dysfunction. Several recent theories have highlighted the neurovascular unit as a potential contributor to the pathophysiology of SZ. We explored the biological plausibility of a link between SZ and the neurovascular system by examining insights gained from genetic, neuroimaging and postmortem studies, which include gene expression and neuropathology analyses. We also reviewed information from animal models of cerebral angiogenesis in order to understand better the complex interplay between angiogenic and neurotrophic factors in development, vascular endothelium/blood brain barrier remodeling and maintenance, all of which contribute to sustaining adequate regional blood flow and safeguarding normal brain function. Microvascular and hemodynamics alterations in SZ highlight the importance of further research and reveal the neurovascular unit as a potential therapeutic target in SZ.

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Section: Regional Brain Hemodynamic Changes Associated With Sz CLImentioning

confidence: 92%

Microvascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection

Katsel

Roussos

Pletnikov

et al. 2017

Neuroscience & Biobehavioral Reviews

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“…These analytes were chosen based on two recent review literatures (Buckley et al , 2007; Lopes et al , 2015). The human proinflammatory 9-plex assay kit measured 9 cytokines and chemokines including GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, and TNF-α in plasma samples, which were chosen based on their implication in schizophrenia from a recent meta-analysis (Miller et al , 2011).…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, there is growing evidence for neurotrophic and angiogenic factors (brain-derived neurotrophic factor, BDNF; vascular endothelial growth factor, VEGF; and basic fibroblast growth factor, bFGF) contributing to the pathophysiology of SZ (Buckley et al , 2007; Almed et al , 2015; Lopes et al , 2015). There are also micro- and macro-vascular abnormalities that are consistently reported in SZ pathology, and angiogenesis may provide a novel biological framework for understanding these changes (Lopes et al , 2015). Given the genetic regulation of these immune, angiogenic, and neurotrophic factors, and due to substantive heritability of SZ, it is important to examine changes in young relatives at familial risk for SZ.…”

Section: Introductionmentioning

confidence: 99%

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

Lizano

Keshavan

Tandon

et al. 2016

Schizophrenia Research

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Schizophrenia (SZ) is a heterogeneous disorder that presents in adolescence, persists into adulthood, and has many clinical features. Recent evidence suggests that abnormalities in inflammatory, neurotrophic, and angiogenic processes may play a role in the etiology of SZ. The identification of molecular biomarkers early in the course of disease is crucial to transforming diagnostic and therapeutic avenues. We investigated 14 molecular analytes focusing on inflammatory, neurotrophic and angiogenic pathways from the plasma of antipsychotic-naïve familial high risk for SZ (FHR; n=35) and first-episode psychosis (FEP; n=45) subjects, in comparison to healthy controls (HC, n=39). We identified distinct alterations in molecular signatures in young relatives at FHR for SZ prior to psychosis onset and FEP subjects. Firstly, the expression of soluble fms-like tyrosine kinase (sFlt-1), an anti-angiogenic factor that binds vascular endothelial growth factor (VEGF), was significantly increased in the FHR group compared to HC, but not in FEP. Secondly, interferon gamma (IFNγ) was significantly reduced in the FEP group compared to HC. Thirdly, network analysis revealed a positive correlation between sFlt-1 and VEGF, suggesting an activation of the angiogenic cascade in the FHR group, which persists in FEP. Our results indicate an angiogenesis and immunological dysfunction early in the course of disease, shifting the balance towards anti-angiogenesis and inflammation.

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“…The plasma concentrations of inflammatory and neurotrophic (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-12p70, IFNg, TNFa, CRP, sFlt-1, VEGF, TGFb) markers were determined using Meso Scale Discovery MULTI-ARRAY technology. These analytes were selected on the basis of their implication in schizophrenia and bipolar disorder (23)(24)(25)(26)(27)(28)(29). For details regarding analyte quality control, see the methods section in the online supplement.…”

Section: Plasma Analyte Assaysmentioning

confidence: 99%

Association of Choroid Plexus Enlargement With Cognitive, Inflammatory, and Structural Phenotypes Across the Psychosis Spectrum

Lizano

Lutz

Ling

et al. 2019

AJP

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The choroid plexus is an important physiological barrier and produces CSF and neurotrophic, angiogenic, and inflammatory factors involved in brain development. Choroid plexus abnormalities have been implicated in both schizophrenia and bipolar disorder. A previous choroid plexus transcriptomic analysis of schizophrenia identified an upregulation of immune and inflammatory genes that correlated with peripheral inflammatory markers. The purpose of this study was to examine choroid plexus volume in probands across the psychosis spectrum and in their first-degree and axis II cluster A relatives, as well as choroid plexus familiality and choroid plexus covariance with clinical, cognitive, brain, and peripheral marker measures. Methods: Choroid plexus volume was quantified (using Free-Surfer) in psychosis probands, their first-degree and axis II cluster A relatives, and healthy control subjects, organized by DSM-IV-TR diagnosis. Analyte, structural connectivity, and genotype data were collected from a subset of study subjects.

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Angiogenesis in the pathophysiology of schizophrenia — A comprehensive review and a conceptual hypothesis

Cited by 24 publications

References 279 publications

Microvascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection

Microvascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection

Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: A preliminary study

Association of Choroid Plexus Enlargement With Cognitive, Inflammatory, and Structural Phenotypes Across the Psychosis Spectrum

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