Pathophysiologic mechanisms in the pathogenesis and clinical course of schizophrenia

It is widely accepted that schizophrenia originates from abnormalities occu rring during the early stages of neural development. Although large studies have revealed behavioral precursors of schizophrenia in childhood, the dis order is usually not evident until patients are in their 20s or 30s. Some p atients will be resistant to typical antipsychotic treatment at this first- onset of schizophrenia; however, treatment resistance develops in the major ity of patients during the course of successive episodes. This ongoing dete rioration suggests that a degenerative process operates during the active p sychotic phase of the illness. This review presents evidence of neurodevelo pmental and neurodegenerative mechanisms for the development of schizophren ia. These data indicate the importance of effective treatment at the first onset of schizophrenia to improve patient outcome. In addition, animal stud ies suggest that treatment with clozapine may prevent the neurodegenerative component responsible for the development of treatment resistance.