Review articleMicrovascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection
Section snippets
Background: role of angiogenesis during neurodevelopment and CNS function
Schizophrenia (SZ) is a disabling psychiatric disorder that affects multiple brain functions, impairs real-world functioning and is only partially responsive to pharmacological treatments.
Although multiple pathological processes in the neurobiology of SZ have been identified to date, including neurotransmitter system dysfunctions (e.g., dopaminergic systems and the glutamatergic system), myelin, immune-response and infectious origins (Arion et al., 2007, Hakak et al., 2001, Harrison and
Regional brain hemodynamic changes associated with SZ clinical symptoms
That the neurovascular system is involved in SZ has been repeatedly documented by neuroimaging studies. 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
Microvascular/blood brain barrier abnormalities in SZ: evidence from postmortem studies
Given strong evidence for hypoperfusion in many cortical regions in SZ it is surprising that evidence of structural abnormalities in microvasculature are rare and inconsistent. This may be explained, at least in part, by differences in the brain regions studied, by methodological differences, and by the complexity of surveying the microvasculature in cerebral cortical tissue quantitatively. Early reports suggested abnormalities in the microvasculature in SZ, such as reduction of retinal
Microvascular/blood brain barrier transcriptome signature associated with SZ
Reports of microarray-based genome-wide gene expression studies in SZ performed on crude brain tissue homogenates have not pinpointed abnormalities in the cerebral vasculature transcriptome. It has been argued (Harris et al., 2008) that the brain vascular endothelium volume represents only 1–3% of the brain volume (depending on different estimates (Lauwers et al., 2008)) crude brain tissue homogenates and thus, it is unlikely to contribute to overall transcriptional alteration in the disease
Evidence for vascular component association with SZ from the existing genetic data
SZ is a disorder with estimated heritability ranging from 64 to 90% (Lichtenstein et al., 2009, O'Donovan et al., 2003, Sullivan et al., 2003). SZ is thought to be a highly polygenic disorder where each genetic variant has a very small risk effect. Recently, it has been proposed that the genetic risk for SZ may operate at the pathway level (Sullivan, 2012) and hypothesize that multiple polygenetic variations alter a more limited set of biological pathways in SZ. Intra- and inter-cellular
Neurobehavioral sequelae of mutations of the endothelial cells/microvascular genes
Few studies have evaluated neurobehavioral consequences of manipulation of EC genes. Here, we will review the pertinent reports and will propose the future directions to advance the field.
Perspective: vascular remodeling and hypoxia signaling as risk factors in SZ
Active angiogenic mechanisms elicited by growth factors and tissue remodeling proteins released by neuronal and glial cells promote vascularization and distribution of adequate blood supply during neuro- and glia- genesis and provide for a well-developed and plastic vascular plexus that maintains healthy brain function throughout the lifespan.
While morphometric data on area of coverage, total length, mean density and diameters of cerebral vascular endothelium in individuals with SZ are sparse,
Acknowledgements
This manuscript was supported by NIH grant MH097997 to PK and MP (sub-award) and Veterans Administration MIRECC to VH.
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