Proposal for a noradrenaline hypothesis of schizophrenia

Abstract In this article, we have reevaluated the role of noradrenergic dysfunction in the pathogenesis of schizophrenia in the light of today's neuroscience and clinical data. Neurophysiological, psychophysiological, psychopharmacological, and biochemical findings that have accumulated in last decades indicate that certain noradrenergic dysfunctions play important roles in the pathogenesis of the disorder. Moreover, these findings provide us with consistent evidence for the existence of two syndromes generated by either overactivity or underactivity of the central noradrenaline (NA) system. The former appears to correspond to the type I syndrome (positive symptoms) and the latter to the type II syndrome (negative symptoms). We conclude that the involvement of brain NA in cerebral metabolism and blood flow as well as the amine's role in brain development and neuronal differentiation may provide the mechanisms underlying the disease process in schizophrenia. Development of chemical agents acting specifically on the brain noradrenergic mechanisms may be a promising approach to novel treatments of the disorder.