Neurodevelopment and Schizophrenia

Abstract

The evidence of neuroleptics' antipsychotic action due to their antagonism of dopamine receptors led to the hyperdopaminergic theory of schizophrenia. But the functional disturbance of the dopamine neurons should explain the increase and the reduction of some symptoms at the same time through the D2 receptors blockade. The prodromical manifestations of schizophrenia include abnormal movements which precede and predict the beginning of the disease. They also suggest a dopamine deficit. An injury in the mesocortical dopamine projection during the neural development could result in a functional impairment of the prefrontal cortex which causes the cognitive deficit symptoms. It would result also in an excessive compensatory subcortical dopamine activity which would cause the psychotic symptoms. The evidence in behalf of this physiopathology is complex. The mechanism of the subcortical compensation of the prefrontal dopamine deficit remains unknown. It is necessary to find out which is the exact mechanism of the injury that causes the mesocortical projection loss in the schizophrenia. We have suggested that the injury would depend on the excitotoxicity induced by the perinatal hypoxia which would provoke the selective death of a dopamine neurons subset which are very sensitive during the critical period of the mesencephalic development.