Abstract
Structural neuroimaging studies indicate the volume reductions in the prefrontal, tempral, and limbic regions in the brains of patients with schizophrenia. This article reviews the apoptotic mechanisms in the pathogenesis of these changes in the brain and the pharmacological properties of atypical antipsychotic drugs. Apoptotic mechanisms have been proposed as the pathogenesis of neuropil reduction including the decrease in dendritic spines of the pyramidal neurons of the cortex of the brain in schizophrenia, considered to cause the macroscopic volume reductions. Atypical antipsychotic drugs have the properties of being both proapoptotic and antiapoptotic, e. g., agranulocytosis, that is, the serious side effect of clozapine, has been shown to be derived from the apoptosis of the granulocyts, whereas clozapine has neuroprotective effects via the 5-HT1A agonist, and antioxidative and antiapoptotic actions on neurons. Our recent studies revealed the antioxidative and antiapoptotic actions of olanzapine and clozapine. These neuroprotective effects of atypical antipsychotic drugs may provide invaluable information to develop new therapeutics to ameliorate the histological changes in the brain of schizophrenia patients.
