Neurodevelopmental and neurodegenerative alterations in the pathophysiology of schizophrenia: Focus on neuro-immuno-inflammation

Schizophrenia is a severely impairing psychiatric disorder with a precocious onset, accounting for a conspicuous burden of disability worldwide. With respect to the etiology of schizophrenia, as for other major psychoses, the gene-environment interaction seems to be the most accredited model. In particular, alterations in the immune system have been repeatedly reported, involving both the unspecific and specific pathways of the immune system and suggesting that inflammatory/autoimmune processes might play an important role in the development of the disorder. Relating to this hypothesis, an imbalance in the inflammatory cytokines has been associated with schizophrenia and, more broadly, alterations in the inflammatory and immune systems seem to be already present in the early stages of the disorder. Such phenomenon could be responsible of specific neurodevelopmental abnormalities, which identify the roots of the disorder during brain development, with consequences that do not become clinically evident until adolescence or early adulthood. On the other hand, longitudinal cohort studies on schizophrenic patients demonstrated a progressive loss of grey matter, more evident in the frontal and temporal lobes of the brain. These two perspectives, the neurodevelopmental and neurodegenerative one, are thought to coexist in the complex and still unravelled etiology of schizophrenia, with studies supporting both of them. This chapter aims at providing the state of the art in the field.