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There has been a suggested link between glutamate and schizophrenia for many decades.[Howes et al., 2015] Originally, the hypothesis was that, in schizophrenia, there was simply a lack of glutamatergic neurotransmission, but this has been refined to specifically focus on NMDA receptor dysfunction.[Howes et al., 2015; Stone et al., 2007] The involvement of NMDA receptors in schizophrenia is supported by NMDA-receptor antagonist evidence, as well as evidence obtained using neuroimaging techniques.[Howes et al., 2015; Stone et al., 2007] Integrating the dopamine and glutamate hypotheses of schizophrenia has been a challenge. However, glutamate signalling can be integrated upstream of dopamine signalling in certain regions of the brain, as shown on the slide.[Howes et al., 2015]
References:
Howes O, McCutcheon R, Stone J. Glutamate and dopamine in schizophrenia: an update for the 21st century. J Psychopharmacol 2015; 29 (2): 97–115.
Stone JM, Morrison PD, Pilowsky LS. Glutamate and dopamine dysregulation in schizophrenia – a synthesis and selective review. J Psychopharmacol 2007; 21 (4): 440–452.
Purves D, Augustine GJ, Fitzpatrick D, et al. (eds). Neuroscience. 4th Edition. Sinauer Associates, 2008.