Increasing evidence suggests that abnormalities in glutamatergic transmission may be associated with psychosis risk. Genetic polymorphisms associated with schizophrenia converge on NMDA receptor signalling pathways, and transgenic animal models and human neuroimaging studies have shown the functional impact of these risk alleles. Animal models have also shown that environmental risk factors, such as stress, cannabis use and maternal infection can result in glutamatergic dysfunction, and in vivo magnetic resonance spectroscopy (MRS) studies have detected glutamatergic abnormalities in individuals at clinical or genetic risk of psychosis. Glutamatergic dysfunction may impact on dopaminergic transmission, and ultimately lead to the emergence of psychosis. In this review, the evidence that genetic and environmental risk factors for psychosis impact on glutamatergic transmission is discussed. If glutamatergic abnormalities are present early in the disorder, this suggests that glutamatergic therapies may be useful in psychosis prevention.
Keywords: Glutamate, psychosis, risk, schizophrenia, magnetic resonance spectroscopy, prodromal period, at risk mental state, attenuated psychotic symptoms, dopamine neurons, hippocampus
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