[Current status of biochemical hypotheses in the pathogenesis of schizophrenia]

The search for neurochemical correlates of schizophrenic psychopathology is a major issue of modern multidimensional approaches to the schizophrenic psychoses. The main focus of interest has shifted in recent years from the classical dopamine hypothesis to an increasing set of various neurotransmitter imbalance models of schizophrenic psychoses involving not only the dopaminergic system but also glutamatergic, serotonergic, cholinergic, GABAergic or peptidergic neuron systems. The pharmacology and phenomenology of phencyclidine-induced model psychoses and a substantial body of neurochemical evidence in human schizophrenic brain suggest that reduced glutamatergic transmission is a key feature in the pathobiochemistry of schizophrenic psychoses and might trigger episodic dopamine excess states, the putative correlates of psychotic relapse. Given the multiple types of natural course, of severity and of prognosis, it is almost inescapable to conclude that there will be no unitary biochemical abnormality underlying the schizophrenic psychoses. None of the available biochemical models of schizophrenia pathogenesis is corroborated by sufficient experimental data. The biochemical data gathered so far have not had a major impact on diagnostic or therapeutic considerations in the schizophrenic psychoses.