Serotonin and schizophrenia: A review

Two observations initiated the interest in the role of serotonin in schizophrenia: the structural similarity between LSD and serotonin and the LSD-induced psychosis. This interest was later reinforced by the advent of atypical neuroleptics which, among other mechanisms of action, possess a potent 5-HT₂ antagonism. We review in this paper the clinical evidence for a serotonin dysfunction in schizophrenia, including CSF and postmortem studies of serotoninergic markers, results of pharmacological challenge studies, and the use of 5-HT₂ antagonists in the treatment of the disease. We attempt to integrate the different observations of abnormal serotonin indices within the context of what is known about the interactions between the serotoninergic and the dopaminergic systems. We propose a model which takes into account the suggestion of a cortical serotoninergic hypofunction and a beneficial effect of 5-HT₂ antagonism via modulation of subcortical DA activity.