Transmitter dysfunction during the process of schizophrenia

Transmitters that are primarily or secondarily involved in the pathogenesis of schizophrenia have been extensively studied for many years. This review will focus on the transmitter systems that are known to be directly or ind irectly involved in the mode of action of the novel atypical antipsychotics and clozapine, i.e, the dopaminergic, serotonergic and glutamatergic syste ms. The consequences of transmitter dysfunction for perception and for the ability of the individual to adapt to a constantly changing environment are discussed, and a hypothesis that can explain how a primary cortical defect will progressively involve secondary transmitter dysfunction and spontaneo us dopaminergic sensitization is proposed. According to the suggested hypot hesis for the pathogenesis of development of schizophrenic symptoms, pharma cological treatment strategies should focus on flexible as opposed to rigid modulation of sensorimotor gating. The hypothetical effects of serotonergi c and dopaminergic interactions on sensorimotor gating are illustrated, and the implications of the broader receptor profile of atypical antipsychotic s for the reduced capacity to induce extrapyramidal side-effects and the su pposedly superior effect on cognitive dysfunction and negative symptoms are discussed.