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

Schizophrenia (SZ) is a severe mental disorder poorly elucidated from the etiopathogenesis prism. Recently, several micro- and macro-vascular abnormalities have been consistently implicated in SZ's pathophysiology. Since angiogenesis is involved in several biological functions and is a fundamental process in vascular formation and angioregulation, it can provide a framework in which some etiological factors and susceptibility genes for SZ can be linked together. We performed a comprehensive non-systematic review of the literature to explore the possible link between SZ and angiogenesis from a vascular perspective, taking into account new insights from genetic, molecular, neurochemical, animal, and neuroimaging functional studies. Recent molecular and neuroimaging studies indicate that angiogenesis could be involved in SZ etiopathogenesis through its role in neurogenesis during neurodevelopment, or by angiomodulation of cerebral blood flow (CBF). Furthermore, it has been hypothesized that the epidemiological finding of lesser predisposition of SZ patients to certain types of cancer could be derived by a putative interplay between SZ pathophysiology and angiogenesis. While it is yet unclear how a complex multivariate interplay between angiogenic factors, neurotrophins, dopamine and other neurotransmitters, brain angiogenic inhibitor molecules (BAI1–3) and patterns of regional blood flow may yield to a biological effect, the importance of further investigation and considering them as potential therapeutic targets for SZ is highlighted. [Display omitted]