Nitric Oxide and Schizophrenia: Present Knowledge and Emerging Concepts of Therapy

Schizophrenia is a devastating, chronic brain disorder afflicting about 1% percent of the population. The etiology, neuropathology, and pathophysiology of schizophrenia remain elusive. Intense research has been conducted in order to identify specific biological markers of schizophrenia. The gas nitric oxide (NO) is an important signaling molecule involved in many cellular events that take place in the cardiovascular, immune and nervous systems of animals. This present review aims to show that NO and its metabolites play eminent roles in schizophrenia and have a significant influence on our understanding of the development, progression and, possibly, treatment of the disease. Special emphasis is given to aspects of genetic linkage between NO generating and modulating proteins and schizophrenia, and the impact of NO metabolism on processes known to be disturbed in this neuropsychiatric disorder (i.e., nerve cell migration, formation and maintenance of synapses, N-methyl-D-aspartic acid receptor mediated neurotransmission, adult hippocampal neurogenesis, membrane pathology and cognitive abilities). Although certain alterations of brain NO metabolism are not unique to, or indicative of, schizophrenia, their modulation might be a promising therapeutic option for the future.