title: A quantitative review of the postmortem evidence for decreased cortical N-methyl-D-aspartate receptor expression levels in schizophrenia: How can we link molecular abnormalities to mismatch negativity deficits?
abstract: Evidence suggests that anomalous mismatch negativity (MMN) in schizophrenia is related to glutamatergic abnormalities, possibly involving N-methyl-D-aspartate (NMDA) receptors. Decreased cortical expressions of NMDA receptor subunits have been observed in schizophrenia, though not consistently. To aid with integration and interpretation of previous work, we performed a meta-analysis of effect sizes of mRNA or protein levels of the obligatory NR1 subunit in prefrontal cortex from people with schizophrenia. In schizophrenia compared to unaffected controls the pooled effect size was -0.64 (95% confidence interval: -1.08 to -0.20) for NR1 mRNA reduction and -0.44 (95% confidence interval: -0.80 to -0.07) for NR1 protein reduction. These results represent the first step to a deeper understanding of the region-specific, cell-specific, and stage-specific NMDA receptor hypofunction in schizophrenia, which could be linked to mismatch negativity deficits via transgenic and pharmacological animal models.
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, Australia; School of Psychiatry, University of New South Wales, Sydney, Australia. Electronic address: v.catts@NeuRA.edu.AU.
authors.forename: Vibeke S
authors.initials: VS
authors.lastname: Catts
authors.affiliation: Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Yan Ling
authors.initials: YL
authors.lastname: Lai
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, Australia; School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Cyndi Shannon
authors.initials: CS
authors.lastname: Weickert
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, Australia; School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Weickert
authors.affiliation: Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, Australia; Discipline of Psychiatry, University of Queensland, Brisbane, Australia; Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Stanley V
authors.initials: SV
authors.lastname: Catts
mesh_terms: D000818:Animals; D001344:Autopsy; D005072:Evoked Potentials, Auditory / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D023421:Models, Animal; D017397:Prefrontal Cortex / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Glutamate; Meta-analysis; Mismatch negativity; NMDA receptor; Prefrontal cortex; Schizophrenia