Microvascular anomaly conditions in psychiatric disease. Schizophrenia - angiogenesis connection

•Angiogenesis guides development and maintenance cerebral vasculature and assures adequate regional blood flow and normal brain function.•Multifaceted research implicates cerebral microvasculature as a potential contributor to the pathophysiology of schizophrenia.•Atypical angiogenesis gene expression signature offers support for an anomalous blood brain barrier function in schizophrenia.•The neurobehavioral consequences of cerebral angiogenesis defects in animal models relevant to schizophrenia are discussed.

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 hemodynamic alterations in SZ highlight the importance of further research and reveal the neurovascular unit as a potential therapeutic target in SZ.