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      Mismatch negativity (MMN) and sensory auditory processing in children aged 9–12 years presenting with putative antecedents of schizophrenia

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          Abstract

          Identification of markers of abnormal brain function in children at-risk of schizophrenia may inform early intervention and prevention programs. Individuals with schizophrenia are characterised by attenuation of MMN amplitude, which indexes automatic auditory sensory processing. The current aim was to examine whether children who may be at increased risk of schizophrenia due to their presenting multiple putative antecedents of schizophrenia (ASz) are similarly characterised by MMN amplitude reductions, relative to typically developing (TD) children. EEG was recorded from 22 ASz and 24 TD children aged 9 to 12 years (matched on age, sex, and IQ) during a passive auditory oddball task (15% duration deviant). ASz children were those presenting: (1) speech and/or motor development lags/problems; (2) social, emotional, or behavioural problems in the clinical range; and (3) psychotic-like experiences. TD children presented no antecedents, and had no family history of a schizophrenia spectrum disorder. MMN amplitude, but not latency, was significantly greater at frontal sites in the ASz group than in the TD group. Although the MMN exhibited by the children at risk of schizophrenia was unlike that of their typically developing peers, it also differed from the reduced MMN amplitude observed in adults with schizophrenia. This may reflect developmental and disease effects in a pre-prodromal phase of psychosis onset. Longitudinal follow-up is necessary to establish the developmental trajectory of MMN in at-risk children.

          Highlights

          • Examined MMN (duration deviant) in children purportedly at risk of schizophrenia

          • Greater frontal MMN amplitude for children at risk than typically developing peers

          • Increased MMN contrasts with MMN amplitude reduction in adults with schizophrenia

          • Possible basis in maturational and disease processes in frontal and temporal lobes

          • May index pre-prodromal phase of psychosis onset in children at risk

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          Most cited references63

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            From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment.

            Glutamate is the primary excitatory neurotransmitter in mammalian brain. Disturbances in glutamate-mediated neurotransmission have been increasingly documented in a range of neuropsychiatric disorders including schizophrenia, substance abuse, mood disorders, Alzheimer's disease, and autism-spectrum disorders. Glutamatergic theories of schizophrenia are based on the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists to induce schizophrenia-like symptoms, as well as emergent literature documenting disturbances of NMDAR-related gene expression and metabolic pathways in schizophrenia. Research over the past two decades has highlighted promising new targets for drug development based on potential pre- and postsynaptic, and glial mechanisms leading to NMDAR dysfunction. Reduced NMDAR activity on inhibitory neurons leads to disinhibition of glutamate neurons increasing synaptic activity of glutamate, especially in the prefrontal cortex. Based on this mechanism, normalizing excess glutamate levels by metabotropic glutamate group 2/3 receptor agonists has led to potential identification of the first non-monoaminergic target with comparable efficacy as conventional antipsychotic drugs for treating positive and negative symptoms of schizophrenia. In addition, NMDAR has intrinsic modulatory sites that are active targets for drug development, several of which show promise in preclinical/early clinical trials targeting both symptoms and cognition. To date, most studies have been done with orthosteric agonists and/or antagonists at specific sites. However, allosteric modulators, both positive and negative, may offer superior efficacy with less danger of downregulation.
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              Event-related potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400.

              This paper describes recommended methods for the use of event-related brain potentials (ERPs) in clinical research and reviews applications to a variety of psychiatric and neurological disorders. Techniques are presented for eliciting, recording, and quantifying three major cognitive components with confirmed clinical utility: mismatch negativity (MMN), P300, and N400. Also highlighted are applications of each of the components as methods of investigating central nervous system pathology. The guidelines are intended to assist investigators who use ERPs in clinical research, in an effort to provide clear and concise recommendations and thereby to standardize methodology and facilitate comparability of data across laboratories.
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                Author and article information

                Journal
                Int J Psychophysiol
                Int J Psychophysiol
                International Journal of Psychophysiology
                Elsevier
                0167-8760
                1872-7697
                1 September 2013
                September 2013
                : 89
                : 3
                : 374-380
                Affiliations
                [a ]School of Psychiatry, University of New South Wales, Sydney, Australia
                [b ]Neuroscience Research Australia, Sydney, Australia
                [c ]Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College London, London, United Kingdom
                [d ]Schizophrenia Research Institute, Sydney, Australia
                Author notes
                [* ]Corresponding author at: School of Psychiatry, University of New South Wales, Sydney, Australia. Tel.: + 61 2 8382 1409; fax: + 61 2 8382 1402. Kristin.Laurens@ 123456unsw.edu.au
                Article
                S0167-8760(13)00145-1
                10.1016/j.ijpsycho.2013.05.008
                3807658
                23707338
                79e3dedf-a86b-4644-aa88-fd062d4f53f5
                © 2013 The Authors

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 25 February 2013
                : 2 May 2013
                : 13 May 2013
                Categories
                Article

                Neurology
                event-related potentials,high-risk,psychopathology,development,cognition,biomarker
                Neurology
                event-related potentials, high-risk, psychopathology, development, cognition, biomarker

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